Abstract CT553: Tislelizumab (TIS) versus docetaxel (D) in patients with previously treated advanced non-squamous (non-sq) non-small-cell lung cancer (NSCLC): Subanalysis from the RATIONALE-303 phase 3 randomized clinical study
Authors: Cheng Ying , Huang Dingzhi , Ma Zhiyong , Fan Yun , Wang Jie , Yu Xinmin , Dvorkin Mikhail , Rivalland Gareth , Ma Yiyuan , Wang Yan , Ma Yan , Zhou Caicun 
Published: June 2022

Abstract
Background: At a predefined interim analysis (IA), RATIONALE-303 (NCT03358875) demonstrated improved overall survival (OS) for TIS vs D in the intent-to-treat (ITT), with a manageable safety profile. Disease characteristics, standard of care and treatment/prognosis differ between histologic types of NSCLC. Here, we report on the non-sq population.
Methods: 805 patients with histologically confirmed, advanced NSCLC with progressive disease during or after ≥ 1 platinum (Pt)-containing chemotherapy regimen were randomized (2:1) to TIS 200 mg or D 75 mg/m2 every 3 weeks until disease progression, intolerable toxicity, or withdrawal. Histology (sq vs non-sq) was a randomization stratification factor. Dual primary endpoints were OS in the ITT and PD-L1 ≥ 25% populations. A prespecified IA was conducted after ~426 deaths (76% of planned events). Efficacy and safety were assessed in 435 randomized patients with non-sq histology.
Results: Baseline characteristics of non-sq patients were balanced between treatment arms and similar to the ITT population. As of August 10, 2020, at median follow-up of 20 and 17 months (mo), respectively, median (95% CI) OS was longer with TIS (18.6 mo [15.41, 23.16]) vs D (13.8 mo [9.43, 17.94]) in the non-sq ITT population, and objective response rate (ORR) and duration of response (DoR) were also improved for TIS vs D (Table). 95.5% (TIS) and 97.9% (D) of patients had ≥ 1 treatment-emergent adverse event (TEAE) and 39.0% (TIS) and 70.9% (D) of patients had ≥ Grade 3 TEAEs. The most common TEAEs were anemia, aspartate aminotransferase increased and alanine aminotransferase increased (TIS arm), and alopecia, anemia and neutrophil count decreased (D arm).
Conclusions: TIS prolonged OS, consistent with the overall ITT population, with a favorable safety profile in patients with advanced non-sq NSCLC who progressed after a Pt-containing regimen.
Table Efficacy* TIS (n=287) D (n=148) Median OS, mo (95% CI) 18.6 (15.41, 23.16) 13.8 (9.43, 17.94) OS HR (95% CI)† 0.71 (0.538, 0.929) P=0.0064‡,§ Median PFS, mo (95% CI) 2.5 (2.14, 4.01) 3.6 (2.17, 4.14) PFS HR (95% CI)† 0.84 (0.660, 1.062) P=0.0686‡,§ ORR, n (%) 60 (20.9) 14 (9.5) Median DoR, mo (95% CI) 11.7 (6.80, 14.65) 6.2 (2.10, 7.16) Safety** TIS (n=287) D (n=141) TEAEs ≥ 15% of patients in either arm, n (%) All grades ≥ Grade 3 All grades ≥ Grade 3 Anemia 76 (26.5) 11 (3.8) 56 (39.7) 6 (4.3) AST increased 64 (22.3) 5 (1.7) 18 (12.8) 0 (0.0) ALT increased 63 (22.0) 4 (1.4) 24 (17.0) 0 (0.0) Cough 59 (20.6) 4 (1.4) 25 (17.7) 0 (0.0) Weight decreased 44 (15.3) 2 (0.7) 13 (9.2) 0 (0.0) Decreased appetite 41 (14.3) 3 (1.0) 26 (18.4) 0 (0.0) Hypoalbuminemia 37 (12.9) 0 (0.0) 23 (16.3) 0 (0.0) Nausea 37 (12.9) 0 (0.0) 22 (15.6) 0 (0.0) Constipation 31 (10.8) 0 (0.0) 22 (15.6) 0 (0.0) Asthenia 29 (10.1) 1 (0.3) 29 (20.6) 8 (5.7) Neutrophil count decreased 8 (2.8) 1 (0.3) 53 (37.6) 36 (25.5) White blood cell count decreased 8 (2.8) 0 (0.0) 42 (29.8) 26 (18.4) Neutropenia 7 (2.4) 3 (1.0) 44 (31.2) 38 (27.0) Leukopenia 6 (2.1) 0 (0.0) 38 (27.0) 22 (15.6) Alopecia 0 (0.0) 0 (0.0) 70 (49.6) 2 (1.4) *Efficacy analysis set - non-sq patients; †Stratified; ‡One-sided stratified log-rank test; §Descriptive P-value; **Safety analysis set - non-squamous patients ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI; confidence interval; DoR, duration of response; HR, hazard ratio; mo, months; NE, not evaluable; ORR, objective response rate; PFS, progression-free survival; TEAE, treatment-emergent adverse event Data cut-off: August 10, 2020
Citation Format: Ying Cheng, Dingzhi Huang, Zhiyong Ma, Yun Fan, Jie Wang, Xinmin Yu, Mikhail Dvorkin, Gareth Rivalland, Yiyuan Ma, Yan Wang, Yan Ma, Caicun Zhou. Tislelizumab (TIS) versus docetaxel (D) in patients with previously treated advanced non-squamous (non-sq) non-small-cell lung cancer (NSCLC): Subanalysis from the RATIONALE-303 phase 3 randomized clinical study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT553.