Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA.

Abstract

9501 Background: NIVO + IPI was shown to improve overall survival (OS) and durability of response vs chemo in 1L advanced NSCLC in CheckMate 227 Part 1, regardless of PD-L1 expression. We hypothesized that a limited course of chemo combined with NIVO + IPI could provide rapid disease control while building on the durable OS benefit seen with dual PD-1 and CTLA-4 inhibition. CheckMate 9LA (NCT03215706) is a phase 3 randomized study evaluating NIVO + IPI + 2 cycles chemo vs chemo in 1L stage IV/recurrent NSCLC. Methods: Adults with tx-naive, histologically confirmed stage IV/recurrent NSCLC, ECOG performance status 0–1, and no known sensitizing EGFR/ALK alterations were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles) (n = 361) or chemo (4 cycles) alone (n = 358), stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous). Chemo was based on histology. Pts with non-squamous NSCLC in the chemo-only arm could receive optional pemetrexed maintenance. Pts were treated with immunotherapy until disease progression, unacceptable toxicity, or for 2 y. The primary endpoint was OS; the interim analysis using Lan–DeMets alpha spending function with O’Brien–Fleming boundary was planned at ~80% information fraction (ie, after observing ~322 total events). Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by blinded independent central review, and efficacy by PD-L1 subgroups. Exploratory endpoints included safety/tolerability. Results: Baseline characteristics were balanced across arms. At a preplanned interim analysis (minimum follow-up 8.1 mo), OS was significantly prolonged with NIVO + IPI + chemo vs chemo (HR 0.69, 96.71% CI: 0.55–0.87; P = 0.0006); statistically significant improvements in PFS and ORR were seen. With longer follow-up (minimum 12.7 mo), NIVO + IPI + chemo vs chemo continued to provide longer OS; median 15.6 vs 10.9 mo (HR 0.66, 95% CI: 0.55–0.80); 1-y OS rates were 63 vs 47%. Clinical benefit was consistent across all efficacy measures in key subgroups including by PD-L1 and histology. Grade 3–4 tx-related adverse events were reported in 47 vs 38% of pts in the NIVO + IPI + chemo vs chemo arms, respectively. Conclusions: CheckMate 9LA met its primary endpoint: a statistically significant improvement in OS was observed with NIVO + NSCLC-optimized IPI + a limited course of chemo vs chemo (4 cycles) in 1L advanced NSCLC. No new safety signals were reported. Clinical trial information: NCT03215706 .

Non-interventional LUME-BioNIS study of nintedanib plus docetaxel after chemotherapy in adenocarcinoma non-small cell lung cancer: A subgroup analysis in patients with prior immunotherapy

“…Three immunotherapies targeting the PD-1/PD-L1 axisnivolumab, pembrolizumab and atezolizumabwere initially approved for use in NSCLC as single agents following progression on chemotherapy [6][7][8]. More recently, following positive data from Phase III trials versus chemotherapy alone, approvals have been granted for use in combination with first-line chemotherapy for pembrolizumab (non-squamous and squamous tumors), atezolizumab (non-squamous tumors only), and nivolumab plus ipilimumab (non-squamous and squamous tumors, given with only two cycles of chemotherapy) [6,7,[9][10][11][12][13]. Pembrolizumab is additionally licensed for first-line use as monotherapy in patients with PD-L1 tumor proportion score (TPS) of either ≥50% (EU indication) or ≥1% (US indication) [6,14].…”

Update 2020: Management of Non-Small Cell Lung Cancer

“…Patients with PD-L1 < 1% by TPS also had improved OS, HR 0.61 (95% CI 0.38-0.98) [39]. Alopecia, pruritus Paz Ares [39] CHECKMATE-9LA randomized patients with advanced NSCLC that were treatment naïve to combination immunotherapy, nivolumab plus ipilimumab and two cycles of platinum-doublet chemotherapy versus platinum-doublet chemotherapy [40]. Regardless of PD-L1 expression, the median OS was 14.1 months in the combination versus 10.7 months with chemotherapy alone (HR 0.69, 0.55-0.87).…”

First line Immunotherapy for Non-Small Cell Lung Cancer

“…CHECKMATE-9LA [113] randomized patients with stage IV NSCLC, to nivolumab 360 mg Q3W + ipilimumab 1 mg/kg Q6W + two cycles of chemotherapy or 4 cycles of chemotherapy alone. The chemotherapy used was Cisplatin or Carboplatin combined with Pemetrexed or Paclitaxel.…”

“…The chemotherapy used was Cisplatin or Carboplatin combined with Pemetrexed or Paclitaxel. The data were presented in an abstract format and as a lecture during the American Society of Clinical Oncology (ASCO) 2020 annual meeting [113]. Median OS was 15.6 and 10.9 months, in the immunotherapy-chemotherapy and the chemotherapy only groups, respectively.…”