ELCC21预告

主要是Proffered Paper session里三个，整体上没有大的进展，如前日所言，4月份开始从CheckMate-816到预计6月份的IMPower-010，ICB在eNSCLC领域的果实即将成熟

Date Thu, 25.03.2021 

Time 14:35 - 15:55

96O - Camrelizumab or placebo plus carboplatin and paclitaxel as first-line treatment for advanced squamous NSCLC (CameL-sq): A randomized, double-blind, multicenter, phase III trial

Background

Cytotoxic agents may potentiate immune-checkpoint inhibitors with immunological effects. Camrelizumab plus pemetrexed and platinum is a current standard of care for Chinese patients (pts) with advanced non-squamous NSCLC and negative EGFR/ALK mutation. Here we evaluated first-line camrelizumab plus chemotherapy (chemo) for pts with squamous NSCLC.

Methods

In this double-blind, multicenter, phase III trial, previously untreated pts with histologically or cytologically confirmed stage IIIB-IV squamous NSCLC were randomized 1:1 to receive 4–6 cycles of carboplatin (AUC 5) plus paclitaxel (175 mg/m²) with camrelizumab (200 mg) or placebo every 3 weeks, followed by maintenance therapy with camrelizumab or placebo. The primary endpoint was PFS per IRC. Cross-over after disease progression was allowed for pts allocated placebo plus chemo

Results

Totally, 389 pts (camrelizumab plus chemo, n = 193; placebo plus chemo, n = 196) were included. As of Nov. 06, 2020, pts treated with camrelizumab plus chemo were associated with significantly prolonged IRC-assessed PFS versus placebo plus chemo (median, 8.5 [95% CI 6.9–10.4] vs 4.9 [95% CI 4.2–5.5] months; HR, 0.37 [95% CI 0.29–0.47], one-sided P < 0.0001), with benefit observed in pts with both PD-L1 TPS <1% (HR, 0.49 [95% CI 0.35–0.68]) and ≥1% (HR, 0.34 [95% CI 0.24–0.49]). There was also significant improvement in OS for the camrelizumab plus chemo group (median, NR [18.4–NR] vs 14.5 [95% CI 13.2–16.6] months; HR, 0.55 [95% CI 0.40–0.75], one-sided P < 0.0001). Consistently, confirmed ORR (64.8% [95% CI 57.6%–71.5%] vs 36.7% [95% CI 30.0%–43.9%], P < 0.0001) and DoR (median, 13.1 [95% CI 9.3–15.7] vs 4.4 [95% CI 4.2–4.9] months) per IRC favored the camrelizumab plus chemo group. Grade ≥3 treatment-related adverse events occurred in 73.6% of pts in the camrelizumab plus chemo group and 71.9% in the placebo plus chemo group, with no unexpected adverse effects.

Conclusions

The addition of camrelizumab to chemotherapy significantly prolonged PFS and OS in the first-line setting with an acceptable safety profile, supporting this combination as an additional first-line treatment option for pts with advanced squamous NSCLC.

Clinical trial identification：NCT03668496.

97O - First-Line Pembrolizumab Plus Chemotherapy for Patients With Advanced Squamous NSCLC: 3-Year Follow-up From KEYNOTE-407

Background

Pembrolizumab (pembro) + carboplatin and paclitaxel/nab-paclitaxel significantly improved OS and PFS vs placebo in patients (pts) with previously untreated stage IV squamous NSCLC in the phase III KEYNOTE-407 study (NCT02775435). At protocol-specified final analysis (data cutoff May 9, 2019), HR for OS was 0.71 (95% CI, 0.58–0.88). We report long-term data and outcomes for pts who completed 35 cycles (∼2 y) of treatment.

Methods

Eligible pts were randomized 1:1 (stratified by paclitaxel vs nab-paclitaxel; East Asia vs rest of the world; and PD-L1 TPS ≥1% vs <1%) to receive pembro 200 mg + chemo or placebo + chemo Q3W for 4 cycles, then pembro or placebo for up to a total of 35 cycles. Primary endpoints were OS and PFS per RECIST v1.1 by blinded independent central review.

Results

278 pts were randomized to pembro + chemo and 281 to the placebo + chemo group. As of Sep 30, 2020, median time from randomization to data cutoff was 40.1 (range, 33.1–49.4) mo; 117 (41.6%) pts crossed over from the placebo + chemo group to receive pembro monotherapy. Median OS in the pembro + chemo group was 17.2 vs 11.6 mo for placebo + chemo; HR 0.71 (95% CI, 0.59–0.86). 3-year OS rate was 29.7% vs 18.2%, respectively. Median PFS2 was 13.8 vs 9.1 mo, respectively; HR 0.59 (95% CI, 0.49–0.71; Table). Grade 3–5 AEs occurred in 74.8% of pts in the pembro + chemo group and 70.0% in the placebo + chemo group. Among 55 pts who completed 35 cycles of pembro, ORR was 92.7% (5 CR, 46 PR) and 4 pts (7.3%) had SD. 51 pts (92.7%) were alive, and 1-year OS and PFS after completion of 35 cycles were 96.0% and 82.6%. 7 pts had initiated a second course of pembro at data cutoff.

Conclusions

With ∼3 y of follow-up, pembro + chemo continued to demonstrate durable benefit vs chemo alone without additional toxicity. Most pts who completed 35 cycles had objective responses and were alive at data cutoff. These data continue to support pembro + chemo as first-line treatment in pts with metastatic squamous NSCLC.

Clinical trial identification: NCT02775435.

98O - First-line nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles chemotherapy (chemo) vs 4 cycles chemo in advanced non-small cell lung cancer (aNSCLC): association of blood and tissue tumor mutational burden (TMB) with efficacy in CheckMate 9LA

Background

In CheckMate 9LA (NCT03215706), 1L NIVO + IPI + chemo (2 cycles) significantly improved overall survival (OS) vs chemo (4 cycles) in patients (pts) with aNSCLC regardless of tumor histology or PD-L1 expression. TMB is potentially associated with the clinical efficacy of immune checkpoint inhibitors. We evaluated efficacy by tissue and blood TMB (tTMB/bTMB) in CheckMate 9LA.

Methods

tTMB was evaluated using the FoundationOne CDxTM assay from tissue samples collected prior to enrollment. Plasma samples collected at baseline were used for isolation of circulating cell-free tumor DNA and evaluation of bTMB using the Guardant OMNI platform. TMB was not a stratification factor for randomization. Analyses of OS, progression-free survival (PFS), and objective response rate (ORR) were based on prespecified TMB thresholds (tTMB, 10 mut/Mb; bTMB, 16 and 20 mut/Mb). Analyses were based on the March 9, 2020 database lock (DBL; minimum OS follow-up, 12.7 mo).

Results

Of 711 randomized pts with available TMB data at DBL, 64% had evaluable tTMB and 73% had evaluable bTMB. Baseline characteristics were generally well balanced between all randomized, TMB-evaluable and non-evaluable, as well as TMB-high and TMB-low subgroups (both bTMB and tTMB). Overall, clinical benefit (OS, PFS, ORR) was observed with NIVO + IPI + chemo vs chemo in both TMB-high and TMB-low subgroups (Table). The OS benefit with NIVO + IPI + chemo vs chemo was similar between tTMB ≥10 and <10 mut/Mb, and between bTMB ≥16 and <16 mut/Mb subgroups; a numerically higher OS benefit was seen in bTMB ≥20 vs <20 mut/Mb subgroups. For PFS and ORR, the magnitude of benefit was higher in TMB-high versus TMB-low subgroups for both tTMB and bTMB.

Conclusions

Higher TMB appeared to be associated with improved PFS and ORR benefits of NIVO + IPI + chemo over chemo. OS benefit was generally similar between high and low TMB.

Clinical trial identification: NCT03215706.

166P - First-line anlotinib-based combination treatment for patients with advanced non-small cell lung cancer: A threearm, prospective study

Background

Anlotinib, an oral multi-target TKI antiangiogenic Inhibitor, has been recommended by guidelines for the 3rd line or more treatment of NSCLC in China, but its effectiveness in combination in first-line treatment remains unknown. Therefore, this study aimed to evaluate efficacy and safety of anlotinib in combination with erlotinib, chemotherapy or sintilimab, respectively.

Methods

In this open-label, threearm, prospective study, advanced NSCLC patients with EGFR mutation (Cohort A) receive anlotinib and erlotinib; for patients with EGFR mutation negative, the treatment regimen was anlotinib in combination with chemotherapy (Cohort B) or sintilimab (Cohort C) according to investigator. All patients received treatment until disease progression or treatment intolerance. The primary outcome was ORR, the secondary outcomes were PFS, DCR, OS and safety.

Results

A total of 80 patients were enrolled, in Cohort A 30 patients, Cohort B 28 patients and Cohort C 22 patients. The final follow-up deadline was 20 Dec 2020, In Cohort A, 26 patients achieved confirmed PR, ORR was 92.9%, and DCR was 96.4%. Median PFS was 20.5 months, and 12-month PFS rate was 81.5%. In Cohort B, ORR was 60.0%, while DCR was 96.7%. Median PFS was 13.3 months, and 12-month PFS rate was 55.5%. In Cohort C, medium PFS was 15.6 months. The 18- and 24-month PFS rate was 45.9% and 26.2%, respectively. The median OS of the three arms has not been reached. The most common grade 3 adverse events (AEs) were rash (17.2%), oral mucositis (10.3%), diarrhea (6.9%) and proteinuria (6.9%) in Cohort A, and a grade 4 hypertension was observed. In Cohort B, the most common grade 3 AEs were platelet count decreased (20.0%), leucopenia (16.7%), hand-foot-skin reaction (10.0%), hypertriglyceridemia (10.0%), oral mucositis (6.7%) and thrombus (6.7%). Safety data of Cohort C has been published elsewhere.

Conclusions

This study suggests that anlotinib-based combination therapy for patients with advanced NSCLC might be a new first-line therapy strategy. For EGFR-mutated positive patients, anlotinib plus erlotinib shows good efficacy and tolerability. For EGFR-mutated negative patients, anlotinib combines with chemotherapy or sintilimab also may be a promising first-line treatment.

Clinical trial identification：NCT03628521.