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.

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]

LBA9026 Background: In CheckMate 9LA (NCT03215706), 1L NIVO + IPI combined with 2 cycles of chemo was shown to provide survival benefit vs chemo alone in pts with metastatic NSCLC. Here, we report updated efficacy and safety with a 3-year minimum follow-up, as well as exploratory biomarker analyses from this study. Methods: Adults with stage IV or recurrent NSCLC, no known sensitizing EGFR/ ALK alterations, and ECOG performance status ≤ 1 were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + 2 cycles of chemo (n = 361) or 4 cycles of chemo alone (n = 358). Pts were stratified by tumor PD-L1 expression, sex, and histology. Pts with non-squamous (NSQ) NSCLC in the chemo-alone arm could receive pemetrexed maintenance. Assessments included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). For all pts with NSQ NSCLC and with tissue evaluable for mutational analysis (n = 313), the FoundationOne CDxTM assay was used to identify mutant (mut) or wild type (wt) KRAS and STK11 genes. Exploratory assessments included evaluation of OS and PFS with NIVO + IPI + chemo vs chemo by mutation status and safety. Results: At a minimum follow-up of 36.1 mo (database lock: Feb 15, 2022), pts continued to derive long-term, durable OS benefit with NIVO + IPI + chemo vs chemo (HR, 0.74 [95% CI, 0.62–0.87]); 3-y OS rates were 27% vs 19%. Clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across most subgroups, including by PD-L1 expression level (Table) or histology. In an exploratory analysis in pts evaluable for mutations including KRAS and STK11, OS appeared to be improved with NIVO + IPI + chemo vs chemo (median OS, 16.3 vs 13.1 mo). Similar trends of prolonged OS with NIVO + IPI + chemo vs chemo were also seen in pts with or without KRAS mutation (median OS, mut: 19.2 vs 13.5 mo; wt: 15.6 vs 12.7 mo) or STK11 mutation (mut: 13.8 vs 10.7 mo; wt: 17.8 vs 13.9 mo), respectively. Additional efficacy outcomes will be presented. No new safety signals were identified with extended follow-up. Conclusions: With a 3-year minimum follow-up, 1L NIVO + IPI + chemo demonstrated long-term, durable efficacy benefit vs chemo in pts with metastatic NSCLC. Survival benefit of NIVO + IPI + chemo vs chemo was observed regardless of KRAS and STK11 mutation status. Clinical trial information: NCT03215706. [Table: see text]

LBA4001 Background: NIVO demonstrated superior overall survival (OS) vs chemo in previously treated patients (pts) with ESCC (ATTRACTION-3). We report OS and progression-free survival (PFS) from CheckMate 648, the first global phase III study to evaluate both an immuno-oncology (I-O)/chemo combination and an I-O/I-O combination in advanced ESCC. Methods: Adults with previously untreated, unresectable advanced, recurrent or metastatic ESCC were enrolled regardless of tumor cell PD-L1 expression. Pts were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), or chemo alone. Primary endpoints for both comparisons were OS and PFS per blinded independent central review (BICR) in pts with tumor cell PD-L1 ≥ 1%. Hierarchically tested secondary endpoints included OS and PFS in all randomized pts. Results: 970 pts were randomized to NIVO + chemo, NIVO + IPI, and chemo arms (49% with tumor cell PD-L1 ≥ 1%). With 13 months (mo) minimum follow-up, NIVO + chemo and NIVO + IPI led to statistically significant improvement in OS vs chemo in pts with tumor cell PD-L1 ≥ 1% and all randomized pts (Table). Statistically significant PFS benefit was also observed for NIVO + chemo vs chemo (HR 0.65 [98.5% CI 0.46–0.92]; P = 0.0023) in pts with tumor cell PD-L1 ≥ 1%. PFS in NIVO + IPI vs chemo in pts with tumor cell PD-L1 ≥ 1% did not meet the prespecified boundary for significance. The objective response rate (per BICR) was 53% (NIVO + chemo), 35% (NIVO + IPI), and 20% (chemo) in pts with tumor cell PD-L1 ≥ 1% and in all randomized pts was 47%, 28%, and 27%, respectively; longer median (95% CI) duration of response was observed vs chemo for pts with tumor cell PD-L1 ≥ 1%: 8.4 (6.9–12.4), 11.8 (7.1–27.4), and 5.7 (4.4–8.7) mo and for all randomized pts: 8.2 (6.9–9.7), 11.1 (8.3–14.0), and 7.1 (5.7–8.2) mo, respectively. No new safety signals were identified (Table). Conclusions: NIVO plus chemo and NIVO plus IPI both demonstrated superior OS vs chemo, along with durable objective responses and acceptable safety, in pts with advanced ESCC, and each represents a potential new 1L treatment option. Clinical trial information: NCT03143153. [Table: see text]

520 Background: In the phase 3 CheckMate 9DW study (NCT04039607), 1L NIVO + IPI demonstrated significant overall survival (OS) benefit vs LEN/SOR, higher objective response rate (ORR) with durable responses, and manageable safety in uHCC. We present efficacy by best overall response (BOR) subgroups and baseline characteristics, and additional safety analyses from the preplanned interim analysis. Methods: Patients (pts) with previously untreated HCC not eligible for curative surgical or locoregional therapies, Child-Pugh score 5 or 6, and ECOG performance status 0 or 1 were randomized 1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg Q3W (up to 4 cycles), then NIVO 480 mg Q4W or LEN 8 mg or 12 mg QD or SOR 400 mg BID until disease progression or unacceptable toxicity. NIVO was given for a maximum of 2 years. The primary endpoint was OS; secondary endpoints included ORR and duration of response (DOR) per blinded independent central review (BICR) using RECIST v1.1. Results: A total of 668 pts were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333). At a median follow-up of 35.2 (range 26.8–48.9) months (mo), median OS (95% CI) was 23.7 (18.8–29.4) mo with NIVO + IPI vs 20.6 (17.5–22.5) mo with LEN/SOR (HR 0.79 [95% CI 0.65–0.96]; P = 0.0180). ORR (95% CI) per BICR was significantly higher with NIVO + IPI vs LEN/SOR (36% [31–42] vs 13% [10–17]; P < 0.0001); median DOR (95% CI) was 30.4 (21.2–not estimable [NE]) mo vs 12.9 (10.2–31.2) mo. Survival benefit of NIVO + IPI vs LEN/SOR was observed across BOR subgroups at the 24-week landmark timepoint (Table). In subgroup analyses, ORR (95% CI) per BICR was higher with NIVO + IPI vs LEN/SOR across HCC etiologies (uninfected: 35% [26–44] vs 8% [4–15]; HBV infected: 25% [17–34] vs 17% [10–25]; HCV infected: 50% [39–61] vs 16% [9–25]) and in pts with Barcelona Clinic Liver Cancer stage ≤B (33% [23–43] vs 13% [6–21]) or stage C (37% [31–44] vs 14% [10–19]). Safety data are shown in the Table. Additional exploratory analyses will be presented. Conclusions: These additional analyses from CheckMate 9DW demonstrate the efficacy and manageable safety of 1L NIVO + IPI in uHCC and further support its use as a potential standard-of-care treatment option in this setting. Clinical trial information: NCT04039607 . OS by BOR at week 24 landmark NIVO + IPI LEN/SOR BOR CR + PR (n = 101) SD a (n = 105) PD (n = 47) CR + PR (n = 28) SD a (n = 212) PD (n = 31) Median OS (95% CI), mo NR (44.4–NE) 30.0(23.5–37.8) 16.0(12.0–18.7) 28.3(20.6–NE) 22.5(20.5–24.8) 13.5(8.7–25.3) All treated pts NIVO + IPI (n = 332) LEN/SOR (n = 325) Any-grade/grade 3–4 TRAEs, n (%) 278 (84)/137 (41) 297 (91)/138 (42) Hepatobiliary 44 (13)/35 (11) 15 (5)/10 (3) Cardiovascular 10 (3)/3 (< 1) 138 (42)/39 (12) Hemorrhagic 2 (< 1)/1 (< 1) 20 (6)/5 (2) a Includes non-CR/non-PD. CR, complete response; NR, not reached; PD, progressive disease; PR, partial response; SD, stable disease; TRAE, treatment-related adverse event.

Introduction: Checkpoint inhibitors have demonstrated activity in brain lesions in several tumor types, including NSCLC. CheckMate 227 Part 1 (NCT02477826) met its two independent co-primary endpoints, including improved overall survival (OS) for NIVO + IPI vs histology-based chemotherapy (chemo) in patients (pts) with tumor programmed death ligand 1 (PD-L1) expression ≥ 1%. Benefit was also observed in pts with PD-L1 < 1%. Eligible pts included those with treated, asymptomatic brain metastases (mets). Here we present a post-hoc analysis of efficacy and safety in pts with and without baseline (BL) brain mets. Methods: Eligible pts were chemo-naive, with stage IV or recurrent NSCLC, no known sensitizing EGFR/ALK alterations, and ECOG PS 0–1. Pts with treated brain mets who were asymptomatic for ≥ 2 wks prior to randomization were eligible; corticosteroids equivalent to ≤ 10 mg of prednisone daily were permitted if stable or decreasing for ≥ 2 wks prior to randomization. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 240 mg Q2W, or chemo; pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 360 mg Q3W + chemo, or chemo. Pts were treated until disease progression, unacceptable toxicity, or ≤ 2 y of immunotherapy. Results: BL characteristics were generally similar between pts with and without BL brain mets, except that a greater proportion of pts with BL brain mets were < 65 years of age and had non-squamous histology. Efficacy data are shown in the Table. Any-grade nervous system adverse events were reported in 46% of pts with BL brain mets treated with NIVO + IPI and 42% of those treated with chemo, most were grade 1–2. Conclusion: In this post-hoc analysis of pts with advanced NSCLC, NIVO + IPI appeared to provide similar benefit in pts with and without BL brain mets. No new safety signals were identified. Table.Efficacy by baseline brain metastases in CheckMate 227 Part 1Patients with baseline brain metastasesPatients without baseline brain metastasesNIVO + IPI (n = 69)Chemo (n = 66)NIVO + IPI (n = 514)Chemo (n = 517)OS, median (95% CI), mo18.8 (9.2-29.4)13.7 (10.5-16.2)17.1 (15.3-19.9)13.9 (11.8-15.3)HR (95% CI)0.57 (0.38-0.85)0.76 (0.66-0.88)1-y rates, %575962542-y rates, %44264030PFS,a median (95% CI), mo5.4 (3.1-8.6)5.8 (4.3-8.0)4.9 (4.1-5.7)5.4 (4.5-5.6)HR (95% CI)0.79 (0.52-1.19)0.81 (0.70-0.93)1-y rates, %382132172-y rates, %227206ORR,a %33263328DOR,a median (95% CI), mo24.9 (11.3-NR)8.4 (4.2-13.9)19.6 (15.5-28.6)5.8 (4.8-6.9)1-y rates, %724065262-y rates, %5384610Minimum follow-up was 29.3 mo.aPer BICR. BICR, blinded independent central review; CI, confidence interval; chemo, chemotherapy; DOR, duration of response; HR, hazard ratio; IPI, ipilimumab; mo, month; NIVO, nivolumab; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; y, year. Citation Format: Hossein Borghaei, Adam Pluzanski, Reyes Bernabe Caro, Mariano Provencio, Sjaak Burgers, Enric Carcereny, Keunchil Park, Aurelia Alexandru, Lorena Lupinacci, Randeep Sangha, Judith Raimbourg, Alain Vergnenegre, Konstantinos Syrigos, Fabrice Barlesi, Norbert Frickhofen, Ang Li, Ravi Kasinathan, Luis Paz-Ares. Nivolumab (NIVO) + ipilimumab (IPI) as first-line (1L) treatment for patients with advanced non-small cell lung cancer (NSCLC) with brain metastases: Results from CheckMate 227 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT221.

LBA143 Background: The CheckMate 8HW study met its dual primary endpoint with NIVO + IPI demonstrating superior progression-free survival (PFS) by blinded independent central review (BICR) vs chemotherapy (chemo) in patients (pts) with centrally confirmed MSI-H/dMMR mCRC in the first-line (1L) setting (HR 0.21; 95% CI 0.14–0.32; P < 0.0001). We report first results from the other dual primary endpoint of PFS for NIVO + IPI vs NIVO across all lines of therapy in pts with centrally confirmed MSI-H/dMMR mCRC. Methods: Immunotherapy-naive pts with unresectable or mCRC and MSI-H/dMMR status by local testing who had received 0 or 1 prior line of therapy were randomized 2:2:1 to (i) NIVO (240 mg) Q2W (6 doses, then NIVO 480 mg Q4W), (ii) NIVO (240 mg) + IPI (1 mg/kg) Q3W (4 doses, then NIVO 480 mg Q4W), or (iii) chemo ± targeted therapies. Pts who had received ≥ 2 prior lines of therapy were randomized 1:1 to the NIVO + IPI or NIVO arms. Treatments continued until disease progression or unacceptable toxicity (all arms), or a maximum of 2 years (NIVO ± IPI arms). Results: Across all lines of therapy,707 pts were randomized to NIVO + IPI (n = 354) or NIVO (n = 353); 55% and 52% received study treatment in the 1L setting, respectively. Of all randomized pts, 296 in the NIVO + IPI arm and 286 in the NIVO arm had centrally confirmed MSI-H/dMMR status. With 47.0 months (mo) of median follow-up (range, 16.7–60.5), NIVO + IPI demonstrated clinically meaningful and statistically significant improvement in PFS by BICR vs NIVO (HR 0.62; 95% CI 0.48–0.81; P = 0.0003) and higher 12-, 24-, and 36-mo PFS rates vs NIVO (Table). Objective response rate (ORR) by BICR was significantly higher with NIVO + IPI vs NIVO (71% vs 58%; P = 0.0011; Table); best overall response of progressive disease was reported in 10% and 19% of pts, respectively. No new safety concerns were identified (Table). Conclusions: In the first randomized study to compare dual- vs single-agent immunotherapy in MSI-H/dMMR mCRC, NIVO + IPI demonstrated superior PFS vs NIVO across all lines of therapy, with a manageable safety profile. These results establish NIVO + IPI as the potential new standard-of-care treatment for MSI-H/dMMR mCRC. Clinical trial information: NCT04008030 . Efficacy by BICR (all lines; centrally confirmed MSI-H/dMMR by IHC and/or PCR test) NIVO + IPI(n = 296) NIVO(n = 286) Median PFS (95% CI), mo NR (53.8–NE) 39.3 (22.1–NE) HR (95% CI); P value 0.62 (0.48–0.81); 0.0003 PFS rate (12/24/36-mo), % 76/71/68 63/56/51 ORR, n (%); 95% CI, % 209 (71); 65–76 165 (58); 52–64 P value 0.0011 Safety (all lines; all treated), n (%) NIVO + IPI (n = 352) NIVO (n = 351) Any-grade/grade 3–4 TRAEs 285 (81)/78 (22) 249 (71)/50 (14) Any-grade/grade 3–4 TRAEs leading to discontinuation 48 (14)/33 (9) 21 (6)/14 (4) Treatment-related deaths 2 (< 1) 1 (< 1) IHC, immunohistochemistry; NE, not estimable; NR, not reached; PCR, polymerase chain reaction; TRAE, treatment-related adverse event.

LBA4_PR - Nivolumab (NIVO) + low-dose ipilimumab (IPI) vs platinum-doublet chemotherapy (chemo) as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (NSCLC): CheckMate 227 part 1 final analysis

LBA768 Background: Patients (pts) with MSI-H/dMMR mCRC have poor outcomes with standard chemo ± targeted therapies. NIVO ± IPI are approved in previously treated pts with MSI-H/dMMR mCRC in many countries, based on the phase 2 CheckMate 142 study. CheckMate 8HW (NCT04008030) is a randomized phase 3 study comparing NIVO + IPI with NIVO or chemo in pts with MSI-H/dMMR mCRC. We report progression-free survival (PFS) by blinded independent central review (BICR) at a prespecified interim analysis for NIVO + IPI vs chemo in the 1L setting. Methods: Pts ≥ 18 years with recurrent or mCRC not amenable to surgery and MSI-H/dMMR status per local testing were enrolled across different lines of therapy. Previously untreated pts were randomized 2:2:1 to NIVO (240 mg) + IPI (1 mg/kg) Q3W (4 doses, then NIVO 480 mg Q4W), NIVO (240 mg) Q2W (6 doses, then NIVO 480 mg Q4W), or chemo ± targeted therapies; treatments continued until disease progression or unacceptable toxicity (all arms), or a maximum of 2 years (NIVO ± IPI arms). For pts with BICR-documented progression with chemo, optional crossover to NIVO + IPI was permitted. Dual primary endpoints were PFS by BICR per RECIST v1.1 for NIVO + IPI vs chemo (1L) and NIVO + IPI vs NIVO (all lines) in pts with centrally confirmed MSI-H/dMMR mCRC. Results: In the 1L setting, 303 pts were randomized to NIVO + IPI (n = 202) or chemo (n = 101); of these pts, 171 pts in the NIVO + IPI arm and 84 pts in the chemo arm had centrally confirmed MSI-H/dMMR result by either immunohistochemistry and/or polymerase chain reaction-based tests. With 24.3 months of median follow-up, NIVO + IPI demonstrated clinically meaningful and statistically significant improvement in PFS vs chemo, with a 79% reduction in the risk of disease progression or death (HR 0.21 [95% CI 0.14–0.32]; P < 0.0001) (Table). No new safety signals were identified (Table). Conclusions: NIVO + IPI demonstrated superior PFS vs chemo in previously untreated pts with MSI-H/dMMR mCRC. NIVO + IPI had a different safety profile compared to chemo, with fewer grade 3–4 treatment-related adverse events (TRAEs). These results support 1L NIVO + IPI as a standard-of-care option for pts with MSI-H/dMMR mCRC. Clinical trial information: NCT04008030 . [Table: see text]

O-3 Nivolumab (NIVO) plus chemotherapy (chemo) or ipilimumab (IPI) vs chemo as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): Expanded efficacy and safety analyses from CheckMate 648

Brief Report: First-line Pembrolizumab in Metastatic Non-Small Cell Lung Cancer Habouring MET Exon 14 Skipping Mutation and PD-L1 ≥50% (GFPC 01-20 Study)

4035 Background: NIVO + chemo and NIVO + IPI demonstrated significant overall survival (OS) benefit vs chemo in previously untreated patients (pts) with advanced ESCC in the phase 3 CheckMate 648 study. We report expanded results from the primary analysis with 13-month (mo) minimum follow-up. Methods: Pts with previously untreated, unresectable advanced, recurrent, or metastatic ESCC were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), or chemo. Primary endpoints were OS and progression-free survival (PFS) per blinded independent central review (BICR) in pts with tumor cell programmed death ligand 1 (PD-L1) ≥ 1%. Secondary endpoints planned for hierarchical testing included OS, PFS, and objective response rate (ORR) per BICR in all randomized pts. Duration of response (DOR) per BICR and PFS2 per investigator (time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy, or death) were exploratory endpoints. Results: Among all pts randomized to NIVO + chemo (n = 321), NIVO + IPI (n = 325), or chemo (n = 324), PFS2 favored NIVO + chemo (HR 0.64, 95% CI 0.54–0.77) and NIVO + IPI (HR 0.74, 95% CI 0.62–0.88) vs chemo. ORR (95% CI) was 47% (42–53), 28% (23–33), and 27% (22–32), respectively. More responders with NIVO + chemo or NIVO + IPI vs chemo had prolonged DOR (≥12 mo; 39%, 48%, and 23%, respectively). Efficacy data by tumor cell PD-L1 and PD-L1 combined positive score will be presented. Grade 3/4 treatment-related adverse events with potential immunologic etiology (select TRAEs) occurred in ≤ 6% of pts with NIVO + chemo and NIVO + IPI, and non-endocrine select TRAEs resolved in 57%–95% of pts across organ categories (Table). Conclusions: NIVO + chemo and NIVO + IPI demonstrated favorable PFS2 and a higher proportion of pts with prolonged DOR vs chemo, as well as acceptable safety profiles. These results provide further support for each regimen as a new potential 1L standard of care in advanced ESCC. Clinical trial information: NCT03143153. [Table: see text]

The standard of care for the treatment of patients with advanced NSCLC includes 4-6 cycles of platinum-doublet chemotherapy with or without bevacizumab, with modest improvements in survival. To improve upon outcomes, recent studies have investigated the role of maintenance therapy after first-line chemotherapy. This concept can be divided into continuation and switch maintenance. The majority of studies have shown significant improvements in progression-free survival (PFS) with the addition of maintenance, but the improved PFS has not always resulted in an improvement of overall survival (OS). Two notable exceptions are erlotinib and, for non-squamous NSCLC, pemetrexed. For patients with non-squamous NSCLC who respond or remain stable after four cycles of platinum-doublet chemotherapy, either continuation of pemetrexed (if included in the induction regimen) or switch to pemetrexed as maintenance has been shown to improve OS compared with observation. Whether maintenance pemetrexed improves OS compared with treatment with pemetrexed at progression is unknown. Recent trials suggest that maintenance therapy benefits both patients with initial response and stable disease after chemotherapy. There is insufficient evidence to support recommending the combination of pemetrexed and bevacizumab over maintenance pemetrexed alone as a switch maintenance approach, although the combination seems to be more effective than bevacizumab alone. The ongoing ECOG 5508 trial is examining this question. For both squamous and non-squamous NSCLC, switch maintenance with erlotinib has been shown to improve both PFS and OS, although the improvement is modest. Switch maintenance with docetaxel or continuation maintenance with gemcitabine confers improvements in PFS regardless of histology but has failed to show improvements in OS. For this reason, switch maintenance with erlotinib can be considered in patients with squamous NSCLC. Overall, maintenance therapy may benefit patients with good performance status who complete four cycles of induction chemotherapy with manageable toxicity, but there is insufficient evidence to make this a blanket recommendation for everyone. Maintenance should remain an individual decision between patients and the treating oncologist.

Chemotherapy + PD-1/PD-L1 Blockade Should Be the Preferred Option in the Neoadjuvant Therapy of NSCLC

LBA9025 Background: In CheckMate 227 part 1 (NCT02477826), 1L NIVO + IPI demonstrated long-term, durable survival benefit vs platinum-doublet chemo in patients (pts) with metastatic NSCLC regardless of tumor programmed death ligand 1 (PD-L1) expression level. Here we present the longest reported follow-up (5 y) of a phase 3 trial of 1L combination immunotherapy in metastatic NSCLC. Methods: Adults with previously untreated stage IV or recurrent NSCLC, no known EGFR/ ALK alterations , and an ECOG performance status ≤ 1 were enrolled and stratified by histology. Pts with tumor PD-L1 ≥ 1% were randomized 1:1:1 to NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO (240 mg Q2W), or chemo. Pts with tumor PD-L1 < 1% were randomized 1:1:1 to NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. Pts were treated until progression, toxicity, or ≤ 2 y for immunotherapy. Assessments included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and a novel efficacy endpoint, treatment-free interval. Treatment-free interval was measured in pts who discontinued study therapy (for any reason including treatment completion) and was defined as the time from last study dose to start of subsequent systemic therapy or death, whichever occurred first. Results: Minimum follow-up was 61.3 mo (database lock, Feb 15, 2022). In pts with tumor PD-L1 ≥ 1% (N = 1189), continued long-term OS benefit was seen with NIVO + IPI vs chemo (HR, 0.77 [95% CI, 0.66–0.91]); 5-y OS rates were 24% (NIVO + IPI), 17% (NIVO), and 14% (chemo). OS benefit also continued in pts with tumor PD-L1 < 1% (N = 550) for NIVO + IPI vs chemo (HR, 0.65 [95% CI, 0.52–0.81]); 5-y OS rates were 19% (NIVO + IPI), 10% (NIVO + chemo), and 7% (chemo). Clinical benefit with NIVO + IPI vs chemo was observed across additional efficacy endpoints in the overall population and in pts alive at 5 y (table). PFS, ORR, and DOR with NIVO and NIVO + chemo will be presented. Among pts alive at 5 y in the NIVO + IPI group, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) remained treatment-free ≥ 3 y after discontinuing study therapy; median (range) duration of NIVO ± IPI therapy was 17.7 (0-25.5) mo (PD-L1 ≥ 1%) and 9.5 (0-25.1) mo (PD-L1 < 1%). No new safety signals were observed. Conclusions: With a 5-y minimum follow-up, NIVO + IPI continues to provide long-term, durable clinical benefit vs chemo in previously untreated pts with metastatic NSCLC, regardless of PD-L1 expression. NIVO + IPI led to increased 5-y survivorship; the majority of these pts were treatment-free for ≥ 3 y post-treatment discontinuation. Clinical trial information: NCT02477826. [Table: see text]

92 Background: Nivolumab (BMS-936558/ONO-4538), a fully human IgG4, PD-1 immune-checkpoint inhibitor antibody, has shown durable clinical activity in several tumor types. Recently, two phase III studies (CheckMate-017 and -057) demonstrated that nivolumab improved overall survival (OS) than docetaxel in second-line of squamous (SQ) and non-squamous (NSQ) Non-Small Cell Lung Cancer (NSCLC), respectively. Here, we report the results of a phase II study to evaluate the efficacy and safety of nivolumab in Korean patients (pts) with previously treated advanced SQ and NSQ NSCLC. Methods: This study requires pts aged ≥ 20 years with ECOG Performance Status (PS) of 0 or 1, stage IIIB/IV or recurrent NSCLC and at least one prior chemotherapy including platinum containing regimen. Pts received nivolumab 3 mg/kg IV Q2W until progression or unacceptable toxicity. The primary endpoint in this study was the objective response rate (ORR) (RECIST v1.1). Results: Nivolumab was administered to 100 NSCLC pts (SQ: 44, NSQ: 56), male/female: 78 (SQ: 44, NSQ: 34)/22 (SQ: 0, NSQ: 22); PS 0/1: 14 (SQ: 6, NSQ: 8)/86 (SQ: 38, NSQ: 48); aged 29 to 80 [median: 66.5] years (SQ: 40 to 80 [median: 69.5], NSQ: 29 to 77 [median: 63.5]); Stage IIIB/IV/recurrence: 6 (SQ: 5, NSQ: 1)/91 (SQ: 37, NSQ: 54)/3 (SQ: 2, NSQ: 1)). In SQ and NSQ NSCLC, ORR was 15.9% (7/44) and 23.2% (13/56), respectively. Median progression-free survival was 2.6 mo and 5.3 mo, respectively. Complete Response was observed in 2.3% (1/44) and 1.8% (1/56), respectively. Median OS was 12.3 mo and 16.3 mo, respectively. Median follow-up was 8.9 mo and 12.3 mo, respectively. Most common adverse drug reaction (ADR) was decreased appetite 15.9% (7/44), followed by pyrexia 9.1% (4/44) in SQ NSCLC, and decreased appetite 12.5% (7/56), followed by pruritus 10.7% (6/56), fatigue 8.9% (5/56), pyrexia 5.4% (3/56) and nausea 5.4% (3/56) in NSQ NSCLC. Grade 3-4 ADR was observed in 6.8% (3/44) and 10.7% (6/56) of SQ and NSQ NSCLC, respectively. No interstitial lung disease and no grade 5 ADRs were observed in this study. Conclusions: Nivolumab was considered to be effective and used safely in Korean pts with SQ and NSQ NSCLC as well as in non-Korean pts with SQ and NSQ NSCLC. Clinical trial information: NCT02175017.