Presidential Symposium I
LBA3 - Treatment with tumor-infiltrating lymphocytes (TIL) versus ipilimumab for advanced melanoma: Results from a multicenter, randomized phase III trial
In total, 168 pts, the majority (86%) refractory to anti-PD-1 treatment, were randomized to TIL (n=84) or ipilimumab (n=84). With a median follow-up of 33.0 months, median PFS was 7.2 months for TIL (95% CI, 4.2 - 13.1), compared to 3.1 months (95% CI, 3.0 - 4.3) for ipilimumab (HR: 0.50 [95% CI, 0.35 - 0.72]; P<0.001). Overall RR was 49% (95% CI, 38% - 60%) for TIL and 21% (95% CI, 13% - 32%) for ipilimumab, with 20% (95% CI, 12% - 30%) and 7% (95% CI, 3% - 15%) complete responses, respectively. Median OS for TIL was 25.8 months (95% CI, 18.2 - not reached) and 18.9 months (95% CI, 13.8 - 32.6) for ipilimumab (HR: 0.83 [95% CI, 0.54 - 1.27]; P=0.39). Grade ≥3 treatment-related adverse events occurred in all TIL and 57% of ipilimumab pts.
Presidential Symposium II
LBA4 - Adjuvant nivolumab plus ipilimumab (NIVO+IPI) vs placebo (PBO) for localized renal cell carcinoma (RCC) at high risk of relapse after nephrectomy: Results from the randomized, phase III CheckMate 914 trial
816 pts were randomized to NIVO+IPI (n = 405) vs PBO (n = 411). With 37.0 months of median follow-up (range, 15.4–58.0), the primary efficacy endpoint of DFS was not met (HR, 0.92; 95% CI, 0.71–1.19; p= 0.5347). Median DFS was not reached with NIVO+IPI and 50.7 months with PBO; DFS probabilities at 24 months were 76.4% and 74.0%, respectively. Median (Q1, Q3) treatment duration was 5.1 (2.8, 5.3) months and 5.1 (5.1, 5.3) months, respectively. Any-grade treatment-related adverse events (AEs) were reported in 88.9% vs 56.8% of pts treated with NIVO+IPI vs PBO; grade ≥ 3 treatment-related AEs were reported in 28.5% vs 2.0%, respectively. Treatment-related AEs led to discontinuation of NIVO+IPI in 29.0% of pts and of PBO in 1.0% of pts.
LBA5 - Primary results of the phase III KEYNOTE-412 study: Pembrolizumab (pembro) with chemoradiation therapy (CRT) vs placebo plus CRT for locally advanced (LA) head and neck squamous cell carcinoma (HNSCC)
主要是名字起的不好。。。
804 pts were randomized (402 pts in each arm). Overall, baseline characteristics were well balanced between arms. At data cutoff (May 31, 2022) for the final analysis, median time from randomization to data cutoff was 47.7 (range, 37.0-61.4) mo. There was a favorable trend toward improved EFS with adding pembro vs placebo to CRT (HR 0.83,
LBA6 - Neoadjvuant versus adjuvant pembrolizumab for resected stage III-IV melanoma (SWOG S1801)
A total of 313 patients were randomized: 154 to NAT and 159 to AT. With a median follow-up of 14.7 months, EFS was significantly higher on NAT compared to AT (one-sided log-rank p=0.0015, Cox HR 0.59, 95% confidence interval (CI) 0.40-0.86). With 36 deaths observed (NAT=14, AT=22), overall survival HR was 0.63 (95% CI 0.32-1.24, one-sided p=0.091). Benefit of NAT over AT was consistent across age, sex, performance status, stage, LDH, ulceration and BRAF status. The same proportion of patients made it through surgery to adjuvant PEM in both arms. The rates of adverse events attributed to PEM or surgery were similar in both arms. In the NAT arm, 28 of 132 patients (21%) with submitted pathology reports were noted to have complete pathologic response (0% viable tumor) on local review.
LBA7 - Neoadjuvant immune checkpoint inhibition in locally advanced MMR-deficient colon cancer: The NICHE-2 study
A total of 112 pts were treated. Grade 3-4 immune-related adverse events were observed in 3 (3%) patients and only 3 pts experienced delay in surgery, meeting the safety primary endpoint. In the PP population (n=107), baseline radiologic assessment revealed 89% stage III, 77% high-risk stage III (Table), and 64% T4 tumors. With a median time from first dose to surgery of 5 weeks, pathologic response was observed in 106/107 (99%) pts, consisting of 102/107 (95%) MPR and 4 (4%) PR. PCR was observed in 72/107 (67%) pts. At a median follow-up of 13 months (range 1-57), none of the pts had disease recurrence.
Presidential Symposium III
LBA8 - Phase III study of cabozantinib (C) in combination with nivolumab (N) and ipilimumab (I) in previously untreated advanced renal cell carcinoma (aRCC) of IMDC intermediate or poor risk (COSMIC-313)
针对中高危
From Jun 2019 to Mar 2021, 855 pts were randomized (428, C+N+I; 427, P+N+I); IMDC risk was intermediate for 75% and poor for 25%. The study met the primary PFS endpoint (HR 0.73, 95% CI, 0.57–0.94; p=0.013); median PFS was not reached (NR; 95% CI, 14.0–not estimable) for C+N+I vs 11.3 mo (95% CI, 7.7–18.2) for P+N+I. Prespecified PFS subgroup analyses will be presented. ORR (PITT population) was 43% (95% CI, 37.2–49.2) for C+N+I vs 36% (95% CI, 30.1–41.8) for P+N+I; median duration of response was NR in either treatment group.
Grade 3/4 TRAEs occurred in 73% with C+N+I vs 41% with P+N+I; 3 pts (1%) in each arm had grade 5 TRAEs, and a TRAE led to discontinuation of all treatment components in 12% vs 5%.
LBA9 - Duration of androgen deprivation therapy (ADT) with post-operative radiotherapy (RT) for prostate cancer: First results of the RADICALS-HD trial (ISRCTN40814031)
From 2007 to 2015, 2839 pts, including 492 in the 3-way randomisation, joined RADICALS-HD from UK, Canada & Denmark: median age 66yrs; 23% pT3b/T4; 20% Gleason 8-10, median pre-RT PSA 0.22ng/ml. Of these, 1480 pts contribute to None-vs-Short and 1523 pts to Short-vs-Long. Arms were balanced within each comparison; risk factors were more favourable in None-vs-Short than Short-vs-Long. Median follow-up was 9yrs.
In None-vs-Short, based on 268 MFS events, 6mo ADT did not improve MFS (HR 0.89; CI: 0.69-1.14; 79% vs 80% event-free at 10yrs). Time to salvage ADT was delayed (HR 0.54; CI: 0.42-0.70); OS was not improved (HR 0.88; CI: 0.65-1.19).
In Short-vs-Long, based on 313 MFS events, 24mo ADT improved MFS (HR 0.77; CI: 0.61-0.97; 72% vs 78% at 10yrs). Time to salvage ADT was delayed (HR 0.73; CI: 0.59-0.91); OS was not improved (HR 0.88; CI: 0.66-1.17). Pre-specified subgroup analyses will be presented.
LBA10 - Sotorasib versus docetaxel for previously treated non-small cell lung cancer with KRAS G12C mutation: CodeBreaK 200 phase III study
还没出
LBA11 - IPSOS: Results from a phase III study of first-line (1L) atezolizumab (atezo) vs single-agent chemotherapy (chemo) in patients (pts) with NSCLC not eligible for a platinum-containing regimen
453 pts were randomised (302 atezo; 151 chemo). Median age was 75 yr (range, 33-94), 31% were ≥80 yr, 72% were male and 83% had ECOG PS ≥2. At data cutoff (30 Apr 2022), with a median follow-up of 41.0 mo, atezo significantly improved OS vs chemo (stratified HR, 0.78; 95% CI: 0.63, 0.97; P=0.028), with a consistent benefit seen across key subgroups, including PD-L1 expression levels, PS and histology. Benefit was seen in 2-yr OS rate, ORR and DOR (Table). Gr 3/4 TRAEs occurred in 16.3% and 33.3% of pts and Gr 5 TRAEs in 1.0% and 2.7% of pts in the atezo and chemo arms, respectively. Atezo improved TTCD of chest pain vs chemo (HR, 0.51; 95% CI: 0.27, 0.97); meaningful improvements from baseline were also seen for appetite loss and cough.
Proffered Paper session: Gynaecological cancers
LBA29 - Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC)
537 pts were randomized to ola + bev and 269 to pbo + bev (median follow-up 61.7 and 61.9 mo, respectively; OS data maturity: 55.3%). Median OS in the ITT population was 56.5 mo with ola + bev vs 51.6 mo with pbo + bev (HR 0.92, 95% CI 0.76–1.12; P=0.4118; OS at 5 y, 47.3 vs 41.5%). In HRD+ pts, OS was prolonged with ola + bev (HR 0.62, 95% CI 0.45–0.85; OS at 5 y, 65.5 vs 48.4%), with benefit in HRD+ pts with or without a tumour BRCAm (tBRCAm; Table). No benefit was seen in HRD- pts (HR 1.19, 95% CI 0.88–1.63). Subsequent PARP inhibitor therapy was received by 105 (19.6%) ola + bev pts vs 123 (45.7%) pbo + bev pts. Myelodysplastic syndrome, acute myeloid leukaemia and aplastic anaemia incidence, and new primary malignancy incidence, was respectively: ola + bev, 9 pts [1.6%] and 22 pts [4.1%]; pbo + bev, 6 pts [2.2%]) and 8 pts [2.9%]).
LBA30 - Phase III ATALANTE/ov29 trial: Atezolizumab (Atz) versus placebo with platinum-based chemotherapy (Cx) plus bevacizumab (bev) in patients (pts) with platinum-sensitive relapse (PSR) of epithelial ovarian cancer (OC)
From 10/2016 to 09/2019, 614 pts were randomized to Atz (n=410) or Pbo (n=204). Pts characteristics were balanced; Cx: CbD (63%), CbG (29%), CbP (8%), 1 (74%) or 2 (26%) prior lines, prior bev (62%). PD-L1 status was positive,negative, unknown in 38%,49% and 13% of pts. Median follow-up was 36 m.
The median PFS in the ITT pts was 13.5 and 11.2 m for the Atz and Pbo arms (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99; P = .041), and 15.2 vs 13.1 m in the PD-L1-positive pts (HR, 0.86; 95% CI, 0.63 to 1.16; P = .30). At 333/491 planned events in the ITT pts, the median overall survival (OS) in the Atz and Pbo arms was 35.4 vs 30.6 m (HR, 0.81; 95% CI, 0.65 to 1.01).
Grade ≥3 AEs and immune AEs were reported in 88% vs 86% and in 13% vs 8% of Atz and pbo pts respectively. There were five treatment related AEs of death (Atz, n=3; pbo, n=2). There was no significant difference in global health-related quality of life scores.
LBA31 - Randomized phase III trial of maintenance chemotherapy with tegafur-uracil versus observation following concurrent chemoradiotherapy for locally advanced cervical cancer, GOTIC-002 LUFT trial
Enrollment started in 2010 and completed in 2018. A total of 351 pts from 55 institutions in Japan were randomized either to Arm O (observation only, 178 pts) or Arm UFT ( UFT maintenance，173 pts). Safety data was analyzed in 176 pts in Arm O and 168 pts in Arm UFT. Pts characteristics were well balanced between two arms. Most of pts were stage IIb or IIIb, and received CCRT using weekly cisplatin.
Median PFS did not reach for both arms. Five-year PFS rates were 61.3% (90%CI: 54.8-67.1) for Arm O and 62.0% (90%CI: 55.4-67.8) for Arm UFT (p=0.634). Hazard ratio (HR) of PFS for Arm UFT vs. Arm O was 0.92 (90%CI: 0.69-1.22).
Five-year OS rates were 77.6% (90%CI: 71.8-82.4) for Arm O and 76.1% (90%CI: 70.1-81.1) for Arm UFT (p=0.869). HR of OS for Arm UFT vs. Arm O was 1.04 (90%CI: 0.73-1.47).
All grade adverse events (AEs) occurred significantly more in Arm UFT (93.5%) than Arm O (73.9%) (Odds ratio = 5.05, 95%CI: 2.51, 10.15) but most of them were grade 1 or 2. Incidence of AEs ≥ grade 3 were 15.9% in Arm O and 22.6% in Arm UFT.
Proffered Paper session: Breast cancer, metastatic
LBA15 - MONARCH 3: Interim overall survival (OS) results of abemaciclib plus a nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+, HER2- advanced breast cancer (ABC)
493 pts were randomized to receive NSAI + abemaciclib (n=328) or placebo (n=165). At IA2, with 70.2 months median follow-up, in the ITT the median OS (mOS) was 67.1 months for abemaciclib + NSAI vs 54.5 months for placebo + NSAI (HR=0.754, 95% CI: 0.584-0.974, 2-sided p=0.0301).In the subgroup with visceral disease (sVD), the mOS was 65.1 months for abemaciclib + NSAI vs 48.8 months for placebo + NSAI (HR=0.708, 95% CI: 0.508-0.985; 2-sided p=0.0392). According to the alpha spending procedure, the critical boundaries for declaring significance in both groups were not met for IA2. Follow-up is ongoing for final OS analysis (expected 2023). Safety data were consistent with the known profile of abemaciclib.
LBA16 - Dalpiciclib plus letrozole or anastrozole as first-line treatment for HR+/HER2- advanced breast cancer (DAWNA-2): A phase III trial
456 pts were randomized to dalp + letrozole/anastrozole (N=303) or placebo+ letrozole/anastrozole (N=153). With a median follow-up of 21.7 and 21.4 mo respectively, PFS per INV was significantly improved in the dalp group vs the placebo group (median, 30.6 mo [95% CI 30.6-NR] vs 18.2 mo [16.5-22.5]; HR 0.51 [95% CI 0.38-0.69], 1-sided P <0.0001). PFS benefit with dalp was evident regardless of menopausal status (Table 1). ORR and DoR per INV also favored the dalp group (Table 1). The most frequent grade ≥3 AEs in the dalp group was neutropenia (85.8% [grade 3/4, 64.6%/21.2%] vs 0 in the placebo group) and leukopenia (66.6% [grade 3/4, 65.9%/0.7%] vs 0). SAEs occurred in 11.9% in the dalp group and 6.5% in the placebo group; 4.0% and 2.0% discontinued any treatment due to AEs respectively.
LBA76 - Overall survival (OS) results from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician's choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC)
In total, 543 pts were randomized to receive SG (n=272) vs TPC (n=271). Pts had a median of 3 prior CTs for mBC; 95% had visceral metastases. At data cut-off on July 1, 2022 (median follow-up,12.5 mo), 390 OS events occurred. SG significantly improved OS (median 14.4 vs 11.2 mo; HR, 0.79; P=0.020), ORR, global health status/QoL, and fatigue vs TPC (Table). Safety of SG was consistent with prior reports with no new safety signals identified.
LBA17 - Primary endpoint results of SYNERGY, a randomized phase II trial, first-line chemo-immunotherapy trial of durvalumab, paclitaxel, and carboplatin with or without the anti-CD73 antibody oleclumab in patients with advanced or metastatic triple-negative breast cancer (TNBC)
weekly carboplatin (AUC 1.5) and paclitaxel (80 mg/m2) x12 combined with durvalumab (1500 mg q4w) with (Arm A) or without (Arm B) oleclumab (3000 mg q2w x5 then 3000 mg q4w)
127 pts were recruited and assessed for eligibility (63 in arm A , 64 in arm B) between June 2019 and June 2021 when the recruitment was stopped due to the results of the interim analysis that crossed the futility boundary. Pts under treatment were allowed to continue with durvalumab+/-oleclumab. At data cutoff (July 4, 2022), the median follow-up was 13.2 months with a CBR of 42.9% in arm A and 43.3% in arm B (one-sided Fisher's exact, p=0.61) with no significant difference according to PD-L1 or CD73 status. PFS was not significantly different among arms: median PFS 6 months in arm A vs. 7.7 months in arm B, one-sided log rank test, p=0.89. The safety profile was similar in both arms. 9 patients in each arm are still under immunotherapy maintenance.
The addition of oleclumab to durvalumab with carboplatin/paclitaxel did not increase CBR at week 24 in first-line advanced TNBC. Ongoing translational research aims to better understand the mechanisms of responses to the study combination.
Proffered Paper session: Investigational immunotherapy
LBA37 - A randomized, multicentric phase II study of preoperative nivolumab plus relatlimab or nivolumab in patients with resectable non-small cell lung cancer (NEOpredict-Lung)
From March 4, 2020 to July 15, 2022, 60 patients have been randomized. The primary endpoint was met by all patients. R0 resection rate was 98%, excluding 2 patients with pleural carcinosis, which had been undetected by preoperative imaging. PICIT-related adverse events were as expected with grade ≥ 3 events in 4 (arm A) and 2 (arm B) patients. Two patients treated in arm A died within 90 days of surgery. The 12 months OS rate across both arms was 96% (95% CI: 83-99%), the DFS rate was 91% (78-97%). Radiological response rates were 11% (arm A) and 27% (arm B) per RECIST (full population), and 41% (arm A) and 38% (B) per PERCIST (30 patients from one center). Complete or major histopathological response rates were 28% (arm A) and 32% (arm B). In 60% (arm A) and 71% (arm B) of resections after PICIT ≤ 50% vital tumor cells were observed.
LBA38 - BNT211-01: A phase I trial to evaluate safety and efficacy of CLDN6 CAR T cells and CLDN6-encoding mRNA vaccine-mediated in vivo expansion in patients with CLDN6-positive advanced solid tumours
相比之前，ORR从43%掉到掉到 33% ，DCR从86%掉到 71%
As of 15 Jun 2022, 22 pts had been treated, mainly with testicular (13) and ovarian (4) cancers. 7 pts were treated at dose level (DL) 1 (10^7 CAR T cells/pt; including 1 pt with <10^7 cells) and 13 pts at DL2 (10^8 CAR T cells/pt; including 1 pt with a 50% lymphodepletion regimen and 2 pts with no lymphodepletion).
Proffered Paper session 1: GI, upper digestive
LBA34 - Primary results from the phase III LEAP-002 study: Lenvatinib plus pembrolizumab versus lenvatinib as first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC)
Results 794 pts were randomized (lenva + pembro, 395; lenva, 399). At FA (data cutoff 21 June 2022; median follow-up 32.1 mo), 534 OS events had occurred and 36 pts (9.1%) in the lenva + pembro arm and 24 pts (6.1%) in the lenva arm remained on study treatment. The median OS with lenva + pembro was 21.2 mo vs 19.0 mo with lenva, and the HR was 0.840 (95% CI: 0.708-0.997, P=0.0227, Table). HR for PFS at IA1 (data cutoff 5 April 2021) was 0.867 (95% CI: 0.734-1.024, P=0.0466, Table). ORR at FA was 26.1% for lenva + pembro vs 17.5% for lenva. Grade 3-5 treatment-related adverse events (TRAEs) were 62.5% in the lenva + pembro arm and 57.5% in the lenva arm (grade 5 TRAEs, 1.0% vs 0.8%). Post-study systemic anti-cancer treatments were used in 44.1% vs 52.1% of pts, in each arm, respectively.
LBA35 - Camrelizumab (C) plus rivoceranib (R) vs. sorafenib (S) as first-line therapy for unresectable hepatocellular carcinoma (uHCC): A randomized, phase III trial
Results A total of 543 pts (ITT population) were randomized to receive C+R (N=272) or S (N=271) respectively. With a median follow-up time of 7.8 mo, PFS was significantly improved with C+R vs. S (median 5.6 mo [95% CI 5.5-6.3] vs. 3.7 mo [2.8-3.7]; HR 0.52 [95% CI 0.41-0.65]); 1-sided p<0.0001). With a median follow-up of 14.5 mo, OS was significantly prolonged with C+R vs. S (median 22.1 mo [95% CI 19.1-27.2] vs. 15.2 mo [13.0-18.5]; HR 0.62 [95% CI 0.49-0.80]; 1-sided p<0.0001). ORR, DCR and DoR were also better with C+R vs. S (Table). A pre-specified subgroup analysis showed that HRs of PFS and OS obviously favored C+R in the majority of the subgroups. Grade ≥3 TRAEs occurred in 80.9% with C+R and 52.4% with S. TRAE led to discontinuation of any treatment in 24.3% (of both agents in 3.7%) with C+R and 4.5% with S. Fatal TRAE occurred in 1 pt in each arm.
LBA36 - Final analysis of RATIONALE-301: Randomized, phase III study of tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma
Results A total of 674 pts were randomized (n=342, TIS; n=332, SOR); at data cutoff (11 Jul 2022) minimum study follow up was 33 months (mo). In this final analysis, RATIONALE-301 met its primary endpoint of OS non-inferiority (mOS: 15.9 mo [TIS] vs 14.1 mo [SOR]; stratified HR: 0.85 [95.003% CI: 0.712, 1.019]). TIS was associated with higher ORR (14.3% vs 5.4%) and more durable responses (mDoR: 36.1 mo vs 11.0 mo) compared with SOR. Median PFS with TIS was 2.2 mo and 3.6 mo with SOR (HR: 1.1 [95% CI: 0.92, 1.33]). Median treatment duration was longer with TIS vs SOR (4.1 mo vs 2.7 mo). The safety profiles for both treatments were consistent with prior reports. Incidence rates of grade ≥3 AEs (48.2% vs 65.4%) and AEs leading to discontinuation (10.9% vs 18.5%) were lower with TIS compared with SOR; AEs leading to death were low across both treatments (4.4%, TIS; 5.2%, SOR). Immune-mediated AEs occurring in ≥5% TIS-treated pts were hepatitis (5.3%) and hypothyroidism (5.3%).
Mini Oral session 1: Gynaecological cancers
LBA32 - Efficacy and safety of GX-188E, a therapeutic DNA vaccine, combined with pembrolizumab in HPV 16- and/or 18- positive advanced cervical cancer (phase II): Safe and effective in both PD-L1 positive and negative
A total of 65 patients have been enrolled and 60 patients were analyzed as efficacy population based on having at least one post-baseline tumor assessment. Among 60 patients, 36 patients had PD-L1 positive tumors and 24 patients were PD-L1 negative. According to BICR evaluation, 19 of 60 patients (31.7%) achieved best overall response; 6 patients had a complete response and 13 patients had a partial response. Especially, in PD-L1 negative population with 24 patients, this combination treatment showed significant efficacy (25.0% ORR). Median DOR was 12.3 months and median OS was 17.2 months. 22 of 65 patients (33.8%) had treatment-related adverse events (TRAEs) of any grade with three patients (4.6%) presenting with grade 3 or 4 TRAEs.
From 3 Jan 2017 to 15 Feb 2019, 778 pts were randomised to atezo (n=390) or pbo (n=388). At primary analysis data cutoff (3 May 2022), median follow-up was 44.7 mo and minimum follow-up was 38.6 mo. No pts remain on study treatment. Baseline characteristics were generally balanced between arms. Median INV-DFS was 57.2 mo (95% CI: 44.6, NE) for atezo and 49.5 mo (47.4, NE) for pbo (HR: 0.93; 95% CI: 0.75, 1.15;
Atezo as adjuvant therapy after resection for pts with RCC with increased risk of recurrence did not improve clinical outcomes vs pbo in the ITT population but had a manageable safety profile.
LBA67 - Phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients (Pts) with renal cell carcinoma (RCC) undergoing nephrectomy (PROSPER, ECOG-ACRIN EA8143), a National Clinical Trials Network trial
Between 2/2017 and 6/2021, 819 pts were randomized to perioperative nivo (n=404) or surgery alone (n=415). Clinical stage at enrollment was 53% cT2, 47% cT3-4, 17% cN1, and 4% cM1; 83% of pts had clear cell RCC. The trial was stopped early by DSMC due to futility. RFS was similar between the arms (HR: 0.97; 95% CI: [0.74 – 1.28]; P1-sided = 0.43). The median RFS was not reached. OS was not mature at the time of analysis but was not statistically different between study arms (HR: 1.48; 95% CI: [0.89 – 2.48]; P1-sided = 0.93). Similar withdrawal rates occurred in both arms, approximately 12% (48/404 patients in nivo arm vs. 50/415 in surgery alone arm). 20% of patients treated with nivo experienced at least one Grade 3-4 AE that could be attributable to nivo, compared with 6% in the control arm. The most common treatment related grade 3-4 AEs were kidney injury (1% vs. 2%), rash (2% vs. 0%), and elevated lipase (4% vs. <1%). There were 15 (4%) deaths from RCC in the nivo arm and 18 (4%) deaths from RCC in the surgery alone arm.
Perioperative nivo did not improve RFS in RCC patients at high risk for recurrence.
Proffered Paper session: Breast cancer, early stage
LBA13 - Nivolumab and ipilimumab in early-stage triple negative breast cancer (TNBC) with tumor-infiltrating lymphocytes (TILs): First results from the BELLINI trial
A partial radiological response (PR) after 4 weeks was evident in 7/31 (23%) patients, of which 3 received nivo and 4 nivo/ipi. In the 3 patients that went for surgery after ICB, we observed 1 pCR and 1 near-pCR. Only 6% of the patients developed a grade 3-4 adverse event. Immune activation was detected in 18/31 patients (58%), of which 9 received nivo and 9 nivo/ipi. All patients with a PR had TIL levels above 40%. Patients with a PR had higher baseline expression of IFNG (p=0.014). While baseline CD8+ T cell levels did not correlate with response, spatial analyses revealed that having CD8+ T cells more adjacent to tumor cells was strongly associated with response (p=0.0014). ctDNA clearance at 4 weeks was evident in 24% of the patients.
The majority of TNBC patients with TILs showed increased immune activation after only 4 weeks of ICB and a substantial fraction experienced a clinical response, highlighting the potential of ICB without CTx for TNBC patients.
Proffered Paper session: GU tumours, prostate
LBA62 - Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide (ENZ) + AAP for metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy (ADT): Overall survival (OS) results of 2 randomised phase III trials from the STAMPEDE protocol
Between Nov 2011 & Jan 2014, 1003 pts were randomised ADT +/- AAP & between Jul 2014 & Mar 2016, 916 pts were randomised ADT +/- AAP + ENZ. Randomised groups were well balanced across both trials. Pt cohort: age, median 68 years (yr), IQR 63, 72; PSA prior to ADT, median 95.7 ng/ml, IQR 26.5, 346; de novo 94%, relapsed after radical treatment, 6%. In AAP + ENZ trial, 9% had docetaxel + ADT. OS benefit in AAP + ENZ trial, HR 0.65 (CI 0.55‒0.77) p = 1.4×10-6; in AAP trial, HR 0.62 (0.53, 0.73) p = 1.6×10-9. No evidence of a difference in treatment effect (interaction HR 1.05 CI 0.83‒1.32, p = 0.71) or between-trial heterogeneity (I2 p = 0.70). Same for secondary end-points. % (CI) of pts reporting grade 3-5 toxicity in 1st 5 yr: AAP trial, ADT: 38.5 (34.2-42.8), + AAP: 54.4 (50.0-58.8); AAP + ENZ trial, ADT: 45.2 (40.6 – 49.8), + AAP + ENZ: 67.9 (63.5 – 72.2); most frequently increased with AAP or AAP + ENZ = liver derangement, hypertension. At 7 yr in AAP trial (median follow-up: 95.8m), % (CI) pts alive with ADT: 30 (26, 34) versus with ADT + AAP: 48 (43, 52); RMST: ADT: 50.4m, ADT + AAP: 60.6m, p = 6.6 x 10-9.
LBA63 - PRESTO: A phase III, open-label study of androgen annihilation in patients (pts) with high-risk biochemically relapsed prostate cancer (AFT-19)
PRESTO is a randomized phase III, open-label trial in pts with BRPC and PSADT ≤ 9 months (mo), without distant metastases on conventional imaging (NCT03009981). Pts were randomized 1:1:1 to receive a finite 52-week treatment course with ADT, ADT + APA, or ADT + APA + AAP, stratified by PSADT (< 3 vs 3–9 mo), with post-treatment follow-up. The primary endpoint of bPFS (serum PSA > 0.2 ng/mL following treatment) was compared for each experimental arm vs. control. Secondary endpoints included safety, patient-reported quality of life (QOL), time to testosterone (T) recovery (> 50 ng/dL) (TTTR), metastasis-free survival (MFS) and time to castration resistance (TTCR).
504 pts were randomized to ADT alone (N = 167), ADT + APA (N = 168) or ADT + APA + AAP (N = 169).
At first planned interim analysis, both experimental arms significantly prolonged bPFS compared to the control arm (median 24.9 mo for ADT + APA vs 20.3 mo for ADT, HR = 0.52 (95% CI: 0.35–0.77);
median 26.0 mo for ADT + APA + AAP vs 20.0 mo for ADT, HR = 0.48 (95% CI: 0.32–0.71)).
Median TTTR was 3.9, 3.8 and 4.7 mo in ADT, ADT + APA, and ADT + APA + AAP arms, respectively.
The most common grade ≥ 2 adverse event (AE) was hypertension (19.4%, 23.4%, 30.4% in ADT, ADT + APA and ADT + APA + AAP arms, respectively). Eight pts (1.8%) across all treatment arms stopped treatment for AEs. Follow-up for analysis of QOL, MFS and TTCR is ongoing.
Proffered Paper session: Non-metastatic NSCLC and other thoracic malignancies
LBA47 - Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): Updated results from ADAURA
Globally, 682 pts were randomised; osimertinib n=339, PBO n=343.
In this updated analysis, in pts with stage II-IIIA disease DFS HR was 0.23 (95% CI 0.18, 0.30; 242/470 events; 51% maturity); 3-yr DFS rate was 84% with osimertinib vs 34% with PBO.
In the overall population (stage IB-IIIA) DFS HR was 0.27 (95% CI 0.21, 0.34; 305/682 events); 3-yr DFS rate was 85% with osimertinib vs 44% with PBO.
In the osimertinib arm, fewer pts experienced local/regional and distant recurrence vs PBO. CNS DFS HR was 0.24 (95% CI 0.14, 0.42; 63/470 events) in stage II-IIIA.
The long-term safety profile remains consistent with the known profile of osimertinib.
LBA48 - Community-based mass screening with low-dose CT for lung cancer in Guangzhou
11,708 participants were screened, comprising 5,452 males and 6,256 females with a median age of 59 (IQR, 51-65) years. 189 (1.6%) LCs were diagnosed, among which 162 (85.7%) cases were in stage 0-I. Only 37 (19.6%) and 105 (55.6%) of diagnosed cases met the criteria per NCCN and Chinese screening guidelines, respectively. We found seven independent risk/protective factors for LC through multivariate adjustment (Table).
Using these variables combined with CEA, the model presented an AUC of 0.71 (95%CI, 0.67-0.75), which was significantly higher than that of guidelines in NCCN (0.52, 95%CI 0.50-0.55) and China (0.62 95%CI 0.58-0.67), respectively. Stratified analysis by smoking and stages showed that the AUCs were higher among smokers (0.77, 95%CI 0.71-0.83) and stage I to IV LC (0.74, 95%CI 0.70-0.78, excluding MIA) than in non-smokers (0.69, 95%CI 0.64-0.74) and preinvasive diseases (AIS and MIA, 0.64, 95%CI 0.57-0.72), respectively.
LBA49 - CANOPY-A: Phase III study of canakinumab (CAN) as adjuvant therapy in patients (pts) with completely resected non-small cell lung cancer (NSCLC)
At data cutoff (March 17, 2022), 1382 pts had been randomized to CAN (n=693) or PBO (n=689); baseline characteristics were generally balanced between arms. Median time from randomization to data cutoff was 18.9 months (mo; range 2.8–47.2); for DFS, there were 208 (30.0%) events with CAN and 218 (31.6%) with PBO. DFS was not significantly improved with CAN vs PBO (median 35.0 vs 29.7 mo; HR 0.94; 95% CI 0.78–1.14; one-sided p=0.258).Subgroup analyses (predefined based on demographics, baseline disease characteristics, and biomarkers) did not show any meaningful differences between the two arms for DFS. For OS, only to be formally tested if DFS was statistically significant, there were 44 (6.3%) events with CAN vs 56 (8.1%) with PBO. AEs were Grade ≥3 in 20.8% of pts in CAN arm vs 19.6% in PBO arm and AEs of any grade led to discontinuation in 4.3% of pts (CAN) vs 4.1% (PBO); on-treatment deaths occurred in 1.3% of pts (CAN) vs 2.3% (PBO).
Proffered Paper session 1: GI, lower digestive
LBA21 - FOLFOX/FOLFIRI plus either bevacizumab or panitumumab in patients with initially unresectable colorectal liver metastases (CRLM) and left-sided and RAS/BRAFV600E wild-type tumour: Phase III CAIRO5 study of the Dutch Colorectal Cancer Group
236 pts (118 in each arm) were included in 43 Dutch sites from November 2014 until closure due to futility in March 2022. 6 ineligible pts were excluded. Median follow up was 44 months. Main characteristics were (arm A/B): median age 59/60, male 61/63%, synchronous CRLM 88/92%, prior adjuvant chemotherapy 4/3%, median number of CRLM 12/12. With 197 events, median PFS in arm A vs B was 10.6 vs 10.3 months (stratified HR 1.12, 95% CI 0.84-1.50, p=0.44). Response rate (RR) was 52% vs 76% (p<0.01). Median depth of response (DOR) was 33% vs 49% (p<0.01). R0/1 resection ± ablation rate was 58% vs 56% (p=0.79). Grade ≥3 toxicity occurred in 52% vs 69% (p=0.01), Clavien Dindo grade ≥3 surgical complications in 21% vs 14% (p=0.30).
In first-line treatment of pts with initially unresectable CRLM and left-sided and RAS/BRAFV600E wild-type tumour there is no difference in median PFS between the addition of either bevacizumab or panitumumab to FOLFOX/FOLFIRI. The addition of panitumumab significantly increases RR and DOR but this does not translate in an increased local therapy rate of CRLM.
LBA22 - Phase III study with FOLFIRI/cetuximab versus FOLFIRI/cetuximab followed by cetuximab (Cet) alone in first-line therapy of RAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients: The ERMES study
Co-primary endpoints were non-inferior PFS in the modified per-protocol (mPP) population (pts treated beyond cycle 8) and lower incidence of grade (G) ≥3 AEs for arm B compared to arm A. To test non-inferiority 386 events were needed, and the upper HR boundary was set at 1.33.
From May 2015 to March 2020, 606 pts were randomized: 300 assigned to arm A and 306 to arm B. Median FU was 22.3 (15-33.8) months (m). Drop-out rate was around 40%. In the mPP population (arm B 183/arm A 154) 291 events occurred with mPFS of 10 vs 12.2 m for arm B and A, respectively (HR 1.3, 95%CI 1.03-1.64; p 0.43). In the ITT population (arm B 297/arm A 296) 503 events occurred with mPFS of 9 vs 10.7 m (HR 1.1, 95%CI 0.92-1.31; p 0.39). mOS was 36.6 vs 30.7 m (HR 0.81, 95%CI 0.6-1.09; p 0.22) and 31 vs 25.3 m (HR 0.9, 95%CI 0.72-1.12; p 0.32) in the mPP and ITT population, respectively. G ≥3 AEs were lower in arm B compared to arm A (39.9 vs 44.2%): neutropenia (9.8/14.9%), febrile neutropenia (2.7/5.2%), diarrhea (8.2/11%), oral mucositis (1.6/5.2%), fatigue (0.6/4.6%) and skin disorders (18/20.1%).
The ERMES study does not demonstrate non-inferiority of maintenance with Cet alone. The higher-than-expected drop-out rate and subsequent reduced statistical power might have impaired the results.
LBA23 - Avelumab versus standard second-line treatment chemotherapy in metastatic colorectal cancer (mCRC) patients with microsatellite instability (MSI): The SAMCO-PRODIGE 54 randomised phase II trial
From April 2018 to April 2021, in 49 French sites, 122 pts were enrolled in the mITT population for efficacy analyses (61 in arm A: control; 61 in arm B: avelumab). There were no differences in pts and tumours characteristic between the two arms.No new safety concern in either arms have been detected.
After a median follow-up of 33.3 months (range, 28.3 to 34.8), avelumab was superior to chemotherapy +/- targeted agents with respect to PFS (p=0.025). 12- and 18-month PFS rates were 19% and 9% in arm A, and 31% and 27%, in arm B.
Objective response rates were similar in both arms (28% vs 30%, p=0.45). Among pts with a disease control, 75% in the avelumab group, compared with 20% in the control group, had ongoing disease control at 18 months.
Treatment-related adverse events ≥ grade 3 occurred in 31.7% of the pts in the avelumab group, compared with 53.1% in the control group.
Mini Oral session: NSCLC, metastatic
LBA55 - Trastuzumab deruxtecan (T-DXd) in patients (Pts) with HER2-mutant metastatic non-small cell lung cancer (NSCLC): Interim results from the phase 2 DESTINY-Lung02 trial
At DCO (03/24/2022), 52 and 28 pts in the PEC were randomized and 101 and 50 pts in the SAS were treated with T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up duration was 5.6/5.4 mo and 3.8/3.9 mo. In the PEC, cORR was 53.8% (95% CI, 39.5-67.8%) and 42.9% (95% CI, 24.5-62.8%) in pts receiving T-DXd 5.4 or 6.4 mg/kg, respectively (Table). Treatment-emergent adverse events (TEAEs) were higher with T-DXd 6.4 mg/kg vs 5.4 mg/kg in the PEC and SAS (median treatment duration: 4.7/5.5 mo and 3.3/3.7 mo). In the SAS, any-grade adjudicated drug-related interstitial lung disease occurred in 5.9% and 14.0% of pts receiving T-DXd 5.4 or 6.4 mg/kg, respectively.
LBA56 - MEDI5752 or pembrolizumab (P) plus carboplatin/pemetrexed (CP) in treatment-naïve (1L) non-small cell lung cancer (NSCLC): A phase Ib/II trial
Patients (pts) were enrolled into randomized (R) and single arm (S) cohorts. In the R cohort, pts received CP x 4, followed by pemetrexed maintenance + either 1500 mg Q3W MEDI5752 (M1500+C) or P (P+C). In the later S cohort, pts received 750 mg Q3W MEDI5752 + CP (M750+C). The primary endpoint was objective response rate (ORR) per RECIST v1.1.
As of 12 July 2022, 105 pts were enrolled. We present the results in 91 pts: 41 pts in the R cohort, and the first 50 pts in the S cohort with at least 8 weeks of follow-up. Baseline characteristics were similar between M1500+C (n=20; 45% PD-L1<1%) and P+C cohorts (n=21; 47.6% PD-L1<1%). DOR, PFS and OS were higher in M1500+C vs P+C in ITT and PD-L1<1% (see table).
High Gr3 TRAE (70%) and discontinuation due to TEAE (TEAE-DC; 70%) at M1500+C led to exploring a lower dose of MEDI5752. In M750+C (n=50; 70% PD-L1<1%), at median follow-up of ∼3.9 months, emerging efficacy shows 44% ORR in ITT and 48% in PD-L1<1% and improved safety profile (Gr3 TRAE 32%, TEAE-D/C 20%). M1500+C and M750+C led to greater increase in T cell proliferation (and clonal expansion in M1500+C) than P+C, consistent with pharmacodynamic (PD) effects of CTLA-4 blockade; clonality data on M750+C pending.
LBA57 - Sintilimab plus anlotinib versus platinum-based chemotherapy as first-line therapy in metastatic NSCLC (SUNRISE): An open label, multi-center, randomized, phase II study
Between Nov. 2019 to Jul. 2022, 89 pts were randomized (43 to Arm A, 46 to Arm B). As of Jul. 15th 2022, median follow-up was 13.1 months and 84 pts were evaluable (41 vs 43). ORR was 50.0% (95% CI [33.8-66.2]) in Arm A compared with 32.6% (95% CI [19.1-48.5] in Arm B, with a DoR of 16.3 vs 6.2 mo. DCR was 85.0% (95% CI [70.2-94.3]) vs 93.0% (95% CI [80.9-98.5]), and the median PFS was 10.8 vs 5.7 mo (HR 0.4; 95% CI[0.25-0.74]). OS was not matured. Grade 3-4 treatment-related adverse events(TRAE) occurred in 11.6 % vs 43.5% pts in arm A and B, respectively. Hypothyroidism, hyponatremia and AST increased were most frequently observed in Arm A. 2 pts experienced treatment discontinuation and 1 died due to TRAE in Arm B, while none were observed in Arm A.
LBA59 - Durvalumab (D) ± tremelimumab (T) + chemotherapy (CT) in 1L metastatic (m) NSCLC: Overall survival (OS) update from POSEIDON after median follow-up (mFU) of approximately 4 years (y)
At an updated data cutoff (DCO) of 11 Mar 2022 (mFU 46.5 mo in censored pts), T+D+CT continued to show OS benefit vs CT (HR 0.75; 95% CI 0.63–0.88) with an estimated 25.0% of pts alive at 3 y vs 13.6% (Table). D+CT continued to numerically improve OS vs CT (HR 0.84; 95% CI 0.71–0.99; 3 y OS 20.7%). Consistent with results at the earlier DCO, OS benefit appeared more pronounced with T+D+CT vs CT in pts with non-squamous (than squamous; data will be presented) histology. A trend for OS benefit with T+D+CT vs CT continued to be observed in non-squamous subgroups with mutations (m) in STK11 (Table), KEAP1 or KRAS (data will be presented). No new safety signals were identified based on collection of serious AEs during long-term FU.
Proffered Paper session: NSCLC, metastatic
LBA51 - Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial
We report the results of arm B (gefitinib until the emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation by cobas EGFR Test v2 or progression (PD) by RECIST) and arm C (gefitinib until PD by RECIST), and then switch to osimertinib in both arms. Primary endpoint is Progression Free Survival rate (by RECIST 1.1) “on osimertinib” at 18 months (PFSR-OSI-18). The study was designed to reject a PFSR-OSI-18 of ≤40% in Arm B with 1-sided α = 0.08 and 92% power under a PFSR-OSI-18 of 60%. Arm C was an internal control arm. Secondary endpoints: response rate, overall survival (OS) and Brain PFS (BPFS). The primary analysis was performed in per-protocol (PP) population.
From Nov 2017 to Feb 2020, 52 and 51 patients in 6 countries were randomized to Arm B and C. Most patients were females (75% and 65%), never smokers (71% and 59%) and had EGFR Del19 (64% and 65%), respectively. Median age was 69 and 61 years. One-third of patients had baseline brain metastases. In arm B, 17% of patients (8/47) switched to osimertinib based on ctDNA T790M-positive before RECIST PD. Median follow-up was 30 months. The study met its primary endpoint - PFSR-OSI-18 was 67.2% (84%CI 56.4-75.9%) in arm B vs. 53.5% (84% CI 42.3-63.5%) in arm C, with a median PFS of 22.0 months (95% CI 18.6-NR) vs. 20.2 months (95% CI 14.6-35.0), respectively. The median OS was not reached in arm B vs. 42.8 months (95%CI 27.0-NR) in arm C. Median BPFS in arm B and C were 24.4 months (95% CI 17.9-28.6) and 21.4 months (95% CI 14.5-42.8). Toxicity was as expected for both drugs.
LBA52 - Tepotinib + osimertinib for EGFRm NSCLC with MET amplification (METamp) after progression on first-line (1L) osimertinib: Initial results from the INSIGHT 2 study
As of April 26, 2022, among 425 pre-screened pts, METamp was detected by FISH TBx in 139 (33%) pts and by NGS LBx in 47 (11%) pts. 100 pts received treatment (88 TEP+OSI and 12 TEP; 62% female, median age 61 yrs [20–84], 56% Asian, 68% ECOG PS 1).
Confirmed ORR was 54.5% in 22 FISH METamp TEP+OSI-treated pts with ≥9 months’ follow-up, with 6/12 responders still on treatment. In 48 FISH METamp pts with ≥3 months’ follow-up, ORR was 45.8% (with high rate of NE as BOR; Table). Median DOR was not reached.
In 12 FISH METamp TEP-treated pts, BOR was 1 PR (ORR of 8.3%). 7 pts switched to TEP+OSI at PD and 5 were still on treatment.
Of 88 TEP+OSI-treated pts, 65 (73.9%)/21 (23.9%) had any grade/G≥3 treatment-related AEs (in >15% pts: diarrhea 40.9%/0%, peripheral edema 23.9%/4.5%, paronychia 17.0%/1.1%). Primary reason for discontinuation was AEs in 6 pts (6.8%).
LBA53 - ELIOS: A multicentre, molecular profiling study of patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC treated with first-line (1L) osimertinib
LBA54 - Three years survival outcome and continued cemiplimab (CEMI) beyond progression with the addition of chemotherapy (chemo) for patients (pts) with advanced non-small cell lung cancer (NSCLC): The EMPOWER-Lung 1 trial
At median follow-up of 37.1 months (m; range: 24.0 : 56.5), median OS (mOS) was 23.4 m (19.4, 27.4) for CEMI pts (N=357) vs 13.7 m (11.2, 16.2) for chemo pts (N=355), with hazard ratio (HR) of 0.634 (0.524, 0.768); median progression free survival (mPFS) was 6.3 m (4.6, 8.3) vs 5.3 m (4.3, 6.0), HR 0.560 (0.470, 0.666). 64 pts continued CEMI + chemo as 2L therapy. Continued CEMI + chemo as 2L therapy resulted in a 31.3% objective response rate and a mOS of 15.1 m (11.3, 18.7), and was generally tolerated, with 19 pts (29.7%) experiencing serious treatment-emergent adverse event (TEAE), and 3 pts each with TEAE resulting in discontinuation of study treatment or death.
Proffered Paper session 2: GI, upper digestive
LBA12 - Efficacy of RLY-4008, a highly selective FGFR2 inhibitor in patients (pts) with an FGFR2-fusion or rearrangement (f/r), FGFR inhibitor (FGFRi)-naïve cholangiocarcinoma (CCA): ReFocus trial
As of 01AUG22, 38 pts with FGFR2 f/r, FGFRi naïve CCA were efficacy evaluable. Most pts received the recommended phase 2 dose (RP2D); most (68%) remain on treatment with median duration of 6 months (<0.1 - 18.5 months). Potent efficacy was observed across all doses, particularly at the RP2D with an ORR of 88% (Table). One pt treated at the RP2D had a near-complete response and subsequent tumor resection with curative intent. DOR is not yet mature, with majority of responses ongoing. Across all doses (N=195), the most common treatment-related AEs (TRAEs) were low-grade stomatitis (48%), PPE (46%), and dry mouth (31%). No grade 4/5 TRAEs were observed.
Mini Oral session: Basic science & translational research
LBA72 - Unraveling the mechanism of action and resistance to trastuzumab deruxtecan (T-DXd): Biomarker analyses from patients from DAISY trial
Serotonin receptor pathways in HER2-overexpressing and interferon alpha pathways in HER2-negative area were activated after T-DXd administration. No association between ERBB2 expression and clinical response to T-DXd was observed. No recurrent driver alteration was associated with resistance. ERBB2 hemizygous deletion was detected in 5 out of 88 (6%) patients at baseline; four of them did not respond to T-DXd. SLX4 mutation was acquired in 2 biopsies out of 10 pairs (20%) at progression and was found in 2 samples unmatched with baseline (20%). In two BC cell lines, SLX4 silencing mediated resistance to DXd. T-DXd distribution was observed in 4 out of 6 patients at progression.
Mini Oral session 2: GU tumours, non-prostate
LBA69 - Belzutifan, a HIF-2α Inhibitor, for von Hippel-Lindau (VHL) disease-associated neoplasms: 36 months of follow-up of the phase II LITESPARK-004 study
As of April 1, 2022, 38 of 61 pts (62%) remain on treatment; primary reasons for treatment discontinuation were pt decision (n = 11; 18%) and disease progression (n = 6; 10%). Median follow-up was 37.8 mo (range, 36.1-46.1 mo).
Of 61 pts with RCC, ORR was 64% (95% CI 50.6-75.8; 4 CRs, 35 PRs). Median TTR was 11.1 mo (range, 2.7-30.5 mo), and median DOR was not reached (range, 5.4+ to 35.8+ mo).
Of 22 pts with pNET, ORR was 91% (95% CI 70.8-98.9; 7 CRs, 13 PRs); median DOR was not reached (range, 11.0+ to 37.3+ mo).
Of 50 pts with CNS hemangioblastomas, ORR was 44% (95% CI 30.0-58.7; 4 CRs, 18 PRs); median DOR was not reached (range, 3.7+ to 38.7+ mo). Of 16 evaluable eyes in 12 pts with retinal hemangioblastomas, 100% showed improvement.
Grade 3 treatment-related AEs (TRAEs) occurred in 18% of pts (n = 11); anemia was most common (n = 7; 11%). No grade 4 or 5 TRAEs occurred. No new safety findings were observed with additional follow-up.
Proffered Paper session 2: GI, lower digestive
LBA24 - KRYSTAL-1: Updated efficacy and safety of adagrasib (MRTX849) with or without cetuximab in patients with advanced colorectal cancer (CRC) harboring a KRASG12C mutation
论anti-EGFR mAb对mCRC治疗的关键性
As of Jun 16 2022, 44 pts received ada and 32 pts received ada + cetux.
In the ada mono cohort (median follow-up 20.1 mo), median age was 59 yrs, 50% were female, median prior lines of systemic therapy was 3, 52% and 48% were ECOG PS 0 and 1, respectively. In 43 pts evaluable for efficacy, ORR was 19% (8/43), and DCR was 86% (37/43). Median DOR was 4.3 mo (95% CI 2.3–8.3) and median PFS was 5.6 mo (95% CI 4.1–8.3).
In the ada + cetux cohort (median follow-up 17.5 mo), median age was 60 yrs, 53% were female, median prior lines of systemic therapy was 3, 44% and 56% were ECOG PS 0 and 1, respectively. In 28 pts evaluable for efficacy, ORR was 46% (13/28) and DCR was 100% (28/28). Median DOR was 7.6 mo (95% CI 5.7–NE) and median PFS was 6.9 mo (95% CI 5.4–8.1).
Gr 1–2 and 3–4 TRAEs occurred in 59% and 34% of pts, respectively, in the ada cohort, and 84% and 16% of pts, respectively, in the ada + cetux cohort. No Gr 5 TRAE occurred.
LBA25 - FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer
From 2Sep2020 to 14Dec2021, 691 pts were randomized; F:461 vs P:230. Baseline characteristics were balanced. F significantly improved OS (median: 7.4 m vs 4.8 m P; HR=0.66; [95% CI: 0.55, 0.80]; p<0.001) & PFS (median: 3.7 m vs 1.8 m P; HR=0.32; [95% CI: 0.27, 0.39]; p<0.001). The median duration of follow-up was 11.3 m F vs 11.2 m P. Subsequent anti-cancer therapies were 29.4% F vs 34.3% P. DCR was 55.5% F vs 16.1% P & ORR was 1.5% F vs 0% P. Grade ≥3 adverse events were 62.7% F vs 50.4% P; those occurring in ≥5% on F were hypertension (13.6% vs 0.9% P), asthenia (7.7% vs 3.9% P) & hand-foot syndrome (6.4% vs 0% P).
Proffered Paper session 2: GU tumours, non-prostate
LBA68 - Bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) compared to the investigator’s choice of sunitinib or cabozantinib in previously untreated advanced renal cell carcinoma (RCC): Results from a phase III randomized study (PIVOT-09)
这个设计实在是 狂妄~
Primary endpoints were objective response rate (ORR) by blinded independent central review (BICR) ？？？and overall survival (OS) in pts with IMDC intermediate (I) or poor (P) risk, and in IMDC all-risk disease. The overall study α is 0.05 (2-sided), which is split with 0.001 for ORR and 0.049 for OS.
623 pts (IMDC I/P n=514; IMDC favorable n=109) were randomized and 616 pts (IMDC I/P n=509; IMDC favorable n=107) received ≥1 dose of treatment (sunitinib n=221; cabozantinib n=85).
Efficacy results for the IMDC I/P groups are reported. At a median duration of follow-up of 15.5 months, ORR was 23.0% for BEMPEG + NIVO vs 30.6% for the TKI arm.
OS in IMDC I/P with p-value of 0.19 did not pass the pre-specified alpha of 0.01 at the interim analysis. mOS was 29.0 months for BEMPEG + NIVO and not reached for the TKI arm (HR=0.82, 99% CI: 0.56-1.21).
In IMDC all-risk group, the most common treatment-related adverse events (TRAEs, >20%) of any grade in BEMPEG + NIVO arm were pyrexia (32.6%), pruritus (31.3%), nausea (24.2%), eosinophilia (23.9%), hypothyroidism (22.9%), rash (22.9%), and arthralgia (20.0%). Grade ≥3 TRAEs occurred in 83 pts (26.8%) and 24 pts (7.7%) discontinued due to TRAEs for BEMPEG or NIVO. Grade 5 TRAEs occurred in 3/310 pts (1.0%).
LBA73 - Study EV-103 Cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC)
149 pts were treated: EV+P n=76; EV n=73. Confirmed ORR (95%CI) for EV+P, 64.5% (52.7, 75.1), median DOR was not reached. Confirmed ORR (95%CI) for EV, 45.2% (33.5, 57.3) and median DOR (95%CI) 13.2 mos (6.1, 16.0). TRAEs of special interest included skin reactions (EV+P, n=51 [67.1%]; EV, n=33 [45.2%]), peripheral neuropathy (EV+P, n=46 [60.5%]; EV, n=40 [54.8%]), ocular disorders (eg, dry eye and blurred vision; EV+P, n=20 [26.3%]; EV, n=21 [28.8%]), and hyperglycemia (EV+P, n=11 [14.5%]; EV, n=8 [11.0%]). The majority of treatment-related AESIs were Grade ≤2.
Mini Oral session: GI, lower digestive
LBA26 - BREAKWATER safety lead-in (SLI): Encorafenib (E) + cetuximab (C) + chemotherapy (chemo) for BRAFV600E metastatic colorectal cancer (mCRC)
In this updated analysis (May 16, 2022 cutoff), SAEs occurred in 48.1% and 33.3%, and tx-related SAEs (any drug) in 25.9% and 13.3% of pts, in EC + mFOLFOX6 and EC + FOLFIRI, respectively. One DLT (grade ≥3 neutropenia) was seen in EC + FOLFIRI. In EC + FOLFIRI, in the presence of steady-state E, AUClast of irinotecan and its active metabolite, SN-38, decreased by 24.9% and 26.8%, respectively, consistent with a predicted CYP3A-mediated drug interaction. In EC + mFOLFOX6, in the presence of steady state E, AUClast of platinum in plasma and plasma ultrafiltrate, increased by 15% and 6%, respectively. Antitumor activity data are in the table. Conclusions
LBA27 - Additional analyses of MOUNTAINEER: A phase II study of tucatinib and trastuzumab for HER2-positive mCRC
As of 28 Mar 2022, 86 pts received ≥1 dose of study treatment in cohorts A+B and 30 pts in cohort C. The ORR by week 12 in cohort C was 3.3% (95% CI, 0.1, 17.2) with DCR of 80.0%. Twenty-eight of 30 pts (93.0%) crossed over to received TUC + Tras, with cORR of 17.9% (95% CI, 6.1, 36.9). The most common AEs with TUC monotherapy were diarrhoea (33.3%), abdominal pain (20.0%), and fatigue (20.0%), which were grade (gr) 1 or 2; the most common gr ≥3 events were ALT/AST increase (6.7% for both). The most common AE for post-crossover pts was diarrhoea (35.7%) which was gr 1 or 2; the most common gr ≥3 events were ALT/AST increase (7.1% and 10.7%, respectively). There were no fatal AEs with TUC monotherapy or TUC + Tras.
Mini Oral session: Non-metastatic NSCLC and other thoracic malignancies
LBA71 - First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (uMPM): 4-year update from CheckMate 743
At 47.5-month min f/u (database lock [DBL] 6 May 2022), NIVO + IPI continued to show OS benefit vs chemo with 4y OS rates of 16.8% vs 10.7%; 4y PFS rates were 9.0% vs 0%, respectively (Table). High (vs low or mid) BL sMESO level was associated with shorter OS in both arms; NIVO + IPI showed a trend of improved OS vs chemo across BL sMESO levels (HRs [95% CI], high: 0.72 [0.53–0.98], mid: 0.77 [0.56–1.06], low: 0.77 [0.56–1.05], respectively). OS favored NIVO + IPI vs chemo for both wild-type (HRs = 0.67–0.72) and MPM-specific tumor suppressor mutation subgroups (HRs = 0.41–0.55), except SETD2 mutation (HR = 1.37). Consistent with the prior DBL, the most common grade 3/4 immune-mediated adverse events with NIVO + IPI were hepatitis (5%), diarrhea/colitis (4%), and rash (3%).
Proffered Paper session: NETs and endocrine tumours
LBA45 - Randomized open label phase III study comparing the efficacy and safety of everolimus followed by chemotherapy (CT) with streptozotocin (STZ)-5FU upon progression or the reverse sequence, in advanced progressive panNETs: The SEQTOR study (GETNE 1206)
A total of 141 pts were randomized (71 vs 70 for arm A/B). Median age was 58 years (range: 33-83), and 85 (60%) were male. Overall, 20 (14%) pts were WHO G1, 113 (80%) G2, and 8 (5.7%) unknown. ORR to 1st treatment assigned was 11% vs 30% in arms A/B, respectively (p=0.014). Stable Disease was the most common outcome to the 1st treatment with a CBR of 92% and 80% for arms A/B, respectively (p=0.07). The estimated Kaplan Meier 12m PFS1 rate was 69% and 64% in arms A/B, respectively; mPFS1 was 21.5 m (95% CI: 16.9-31.3) and 23.8 m (95% CI: 13.6-30.8) in arms A/B, respectively (p=0.351). The most frequent grade 3-4 adverse events were fatigue (10%), diarrhea (7%) and abdominal pain (7%) in arm A, and fatigue (13%), neutropenia (9%) and abdominal pain (8%) in arm B. Grade 3-4 pneumonitis was 1.5% in both arms. Arm A resulted in a significant increase of any-grade rash (27% vs 8%), infections (15% vs 5%) and lung infection (15% vs 5%).
联系客服
