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8500 Background: Adjuvant platinum-based chemotherapy (chemo) provides only a modest 5-year survival benefit in fully resected, high-risk early-stage NSCLC. We report the primary disease-free survival (DFS) results from the pre-planned interim analysis of IMpower010, a randomized phase 3 open-label trial of adjuvant atezolizumab (atezo; anti–PD-L1) vs best supportive care (BSC) after adjuvant chemo in patients (pts) with early-stage resected NSCLC. Methods: Eligible pts had completely resected (4-12 weeks prior to enrollment) Stage IB (≥4 cm)-IIIA NSCLC (AJCC/UICC v7) and ECOG PS 0-1. A total of 1280 pts were enrolled, and 1269 pts received up to four 21-day cycles of cisplatin-based chemo (plus pemetrexed, docetaxel, gemcitabine or vinorelbine). Of these pts (n=1269), 1005 were subsequently randomized 1:1 to 16 cycles of atezo 1200 mg Q3W or BSC. The primary endpoint of investigator-assessed DFS and secondary endpoint of overall survival (OS) were tested hierarchically: first DFS in the PD-L1 TC ≥1% (SP263) subgroup with Stage II-IIIA disease, then DFS in all randomized pts with Stage II-IIIA disease, then DFS in the ITT population (Stage IB-IIIA) and finally OS in the ITT population. Efficacy assessments were based on randomized pts. Safety was assessed in the safety-evaluable population, defined as pts who received ≥1 dose of atezo or who had ≥1 post-baseline safety assessment if randomized to the BSC arm. Results: At data cutoff (January 21, 2021), median follow-up was 32.2 months in the ITT population. Baseline characteristics were generally balanced between arms. Atezo showed statistically significant DFS benefit vs BSC in the PD-L1 TC ≥1% Stage II-IIIA and all randomized Stage II-IIIA populations; the significance boundary was not crossed for DFS in the ITT population (Table). OS data were immature and not formally tested. Pts in the atezo arm received a median of 16 (range, 1-16) atezo doses. Any-grade AEs occurred in 92.7% (atezo) and 70.7% (BSC); events were Grade 3/4 in 21.8% and 11.5%, respectively. Grade 5 treatment-related AEs occurred in 0.8% of pts in the atezo arm. AEs leading to atezo discontinuation occurred in 18.2% of atezo-treated pts. Conclusions: IMpower010 met its primary endpoint, showing DFS benefit with adjuvant atezo vs BSC after adjuvant chemo in pts with resected Stage II-IIIA NSCLC, with pronounced benefit in the PD-L1 TC ≥1% subgroup. The safety profile of atezo was consistent with prior experience of atezo monotherapy across indications and lines of therapy. Funding: F. Hoffmann-La Roche Ltd. Clinical trial information: NCT02486718. [Table: see text]

We think the series demonstrates the value of the omental method, which offers excellent therapeutic results following an easy surgical procedure. This method extends indications for surgical treatment and decreases the postoperative complications.

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Results From RATIONALE 303: A Global Phase 3 Study of Tislelizumab (TIS) vs Docetaxel (TAX) as Second- or Third-Line Therapy for Patients With Locally Advanced or Metastatic NSCLC Background: Anti-PD-1/L1 therapies have improved OS by 2-4 mo vs TAX in patients (pts) with advanced NSCLC who progressed after platinum regimens. TIS is an anti-PD-1 antibody engineered to minimize FcγR binding on macrophages, a mechanism of T-cell clearance and potential anti-PD-1 resistance. Methods: RATIONALE 303 (BGB-A317-303; NCT03358875) compared efficacy and safety of TIS vs TAX as 2 or 3L therapy for pts with advanced NSCLC. Patients without oncogenic driver mutation who failed at least 1 prior systemic therapy including a platinum regimen were randomized 2:1 to receive TIS 200 mg IV Q3W (Arm A) or TAX 75 mg/m2 IV Q3W (Arm B). Dual primary endpoints were OS in the ITT analysis set and OS in the PD-L1 high (≥25% TC) analysis set. A prespecified interim analysis (IA) was conducted after ≈426 deaths (76% of planned events); in the IA, formal OS superiority testing was conducted only in the ITT. The IA results are presented. Results: Overall, 805 pts were randomized (n=535, TIS; n=270, TAX); demographics were generally balanced between arms. With a 19-mo median follow-up (441 OS events), median OSITT was significantly longer in Arm A vs B (17.2 vs 11.9 mo; HR=0.64 [95% CI: 0.53, 0.78]; P<.0001). OS benefit was also observed in the PD-L1 high analysis set (19.1 vs 11.9 mo; HR=0.52 [95% CI: 0.38, 0.71]) and across most subgroups including histology. In the ITT analysis set, PFS, ORR, and DoR were also improved in Arm A vs B (Table). Anemia (TIS) and alopecia (TAX) were the most commonly reported AEs (Table); pneumonia (TIS) and neutropenia (TAX) were the most common grade ≥3 AEs. AEs leading to death were 6.0% (TIS) and 4.3% (TAX); treatment-related AEs leading to death were 1.5% (TIS) and 1.6% (TAX). Conclusions: RATIONALE 303 demonstrated that, as 2 or 3L therapy in pts with advanced NSCLC, TIS was tolerable and prolonged OS by 5-7 mo with improved PFS and ORR vs TAX regardless of histology or PD-L1 expression. ITT Analysis Set (N=805)Arm A Tislelizumab (n=535)Arm B Docetaxel (n=270)EfficacyMedian OS, mo17.211.9OS difference, mo5.3HR (95% CI)a0.64 (0.53, 0.78)P-valuea,b<0.0001Median PFS, mo4.12.6PFS difference, mo1.5HR (95% CI)a0.64 (0.53, 0.76)P-valuea,b<0.0001cORR, n (%)117 (21.9)19 (7.0)ORR difference, %14.9OR (95% CI)3.71 (2.24, 6.14)P-valued<0.0001cMedian DoR, mo (95% CI)13.5 (8.5, 21.8)6.2 (2.1, 7.2)Adverse event profileAEs occurring in ≥15% of patients in either arm, n (%)All gradeGrade ≥3All gradeGrade ≥3Anemia152 (28.5)18 (3.4)112 (43.4)16 (6.2)Alanine aminotransferase increased106 (19.9)4 (0.7)38 (14.7)0Cough104 (19.5)5 (0.9)40 (15.5)1 (0.4)Aspartate aminotransferase increased101 (18.9)5 (0.9)31 (12.0)1 (0.4)Appetite decreased82 (15.4)5 (0.9)59 (22.9)3 (1.2)Weight decreased81 (15.2)4 (0.7)26 (10.1)0Alopecia5 (0.9)0122 (47.3)2 (0.8)Neutrophil count decreased15 (2.8)3 (0.6)95 (36.8)71 (27.5)Neutropenia9 (1.7)3 (0.6)81 (31.4)72 (27.9)White blood cell count decreased20 (3.7)1 (0.2)74 (28.7)47 (18.2)Leukopenia15 (2.8)1 (0.2)69 (26.7)41 (15.9)Asthenia67 (12.5)6 (1.1)56 (21.7)14 (5.4)Constipation65 (12.2)042 (16.3)0Hypoalbuminemia70 (13.1)041 (15.9)1 (0.4)Nausea59 (11.0)041 (15.9)1 (0.4)Abbreviations: AE, adverse event; DoR, duration of response; HR, hazard ratio; ITT, intent-to-treat; mo, months; NA, not available; OR, odds ratio; ORR, objective response rate; PFS, progression-free survival.aStratified.bOne-sided log-rank test.cDescriptive P-value.dCochran-Mantel-Haenszel. Citation Format: Caicun Zhou, Dingzhi Huang, Xinmin Yu, Yunpeng Liu, Yun Fan, Yongqian Shu, Zhiyong Ma, Ziping Wang, Ying Cheng, Jie Wang, Sheng Hu, Zhihua Liu, Mikhail Dvorkin, Elena Poddubskaya, Umut Disel, Andrey Akopov, Yiyuan Ma, Yan Wang, Zhenyu Pan, Cunjing Yu, Gareth Rivalland. Results from RATIONALE 303: A global phase 3 study of tislelizumab (TIS) vs docetaxel (TAX) as second- or third-line therapy for patients with locally advanced or metastatic NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT039.

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