Abstract CT554: Tislelizumab (TIS) versus docetaxel (D) in patients with previously treated advanced squamous (sq) non-small-cell lung cancer (NSCLC): Sub-analysis from phase 3 RATIONALE-303 randomized clinical study
Authors: Wang Jie , Ma Zhiyong , Huang Dingzhi , Fan Yun , Yu Xinmin , Hu Sheng , Wang Ziping , Liu Zhihua , Cabuk Devrim , Gumus Mahmut , 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) population with a manageable safety profile. Given disease characteristics, standard of care treatment/prognosis differ between histologic types of NSCLC. Here we report the data on the sq population.
Methods: 805 patients (pts) 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 IV or D 75 mg/m2 IV every 3 weeks until disease progression, intolerable toxicity, or withdrawal. Histology (sq vs non-sq), was a stratification factor for randomization. Dual primary endpoints were OS in the ITT and PD-L1 ≥ 25% populations. The IA was conducted after ~426 deaths (76% of planned events). Efficacy and safety were assessed in 370 randomized pts with sq histology.
Results: Baseline characteristics of sq pts were balanced between treatment arms and similar to the ITT population. As of August 10, 2020, at median follow-up of 19.0 and 19.3 months (mo), respectively, median (95% CI) OS was longer with TIS (16.0 mo [13.8, 18.9]) vs D (11.3 mo [8.7, 12.7]) in the sq ITT population, and progression free survival (PFS), objective response rate (ORR) and duration of response (DoR) were also improved for TIS vs D (Table). 95.1% (TIS) and 99.1% (D) of pts had ≥ 1 treatment-emergent adverse event (TEAE) and 38.1% (TIS) and 79.5% (D) of pts had ≥ Grade 3 TEAEs. The most common TEAEs were anemia, cough and alanine amino transferase increased (TIS arm), and anemia, alopecia, and neutrophil count decreased (D arm).
Conclusions: TIS prolonged OS with a favorable safety profile in pts with advanced sq NSCLC who progressed after a Pt-containing regimen. The data are consistent with the overall ITT population.
Efficacy* TIS (n=248) D (n=122) Median OS, mo (95% CI) 16.0 (13.80, 18.86) 11.3 (8.67, 12.68) OS HR (95% CI)† 0.58 (0.436, 0.761) P &lt; 0.0001‡§ Median PFS, mo (95% CI) 6.2 (4.21, 6.37) 2.3 (2.10, 3.38) PFS HR (95% CI)† 0.45 (0.343, 0.577) P &lt; 0.0001‡§ ORR, n (%) 57 (23.0) 5 (4.1) Median DoR, mo (95% CI) 16.7 (8.31, NE) 6.2 (2.10, 8.31) Safety** TIS (n=247) D (n=117) TEAEs ≥ 20% of patients in either arm, n (%) All grades ≥ Grade 3 All grades ≥ Grade 3 Anemia 76 (30.8) 7 (2.8) 56 (47.9) 10 (8.5) Decreased appetite 41 (16.6) 2 (0.8) 33 (28.2) 3 (2.6) Asthenia 38 (15.4) 5 (2.0) 27 (23.1) 6 (5.1) White blood cell count decreased 12 (4.9) 1 (0.4) 32 (27.4) 21 (17.9) Leukopenia 9 (3.6) 1 (0.4) 31 (26.5) 19 (16.2) Neutrophil count decreased 7 (2.8) 2 (0.8) 42 (35.9) 35 (29.9) Alopecia 5 (2.0) 0 (0.0) 52 (44.4) 0 (0.0) Neutropenia 2 (0.8) 0 (0.0) 37 (31.6) 34 (29.1) *Efficacy analysis set - Sq patients; †Stratified; ‡One-sided stratified log-rank test; §Descriptive P-value; **Safety analysis set - Sq patients CI; confidence interval; D, docetaxel; DoR, duration of response; HR, hazard ratio; mo, months; NE, not evaluable; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; sq, squamous; TEAE, treatment-emergent adverse event; TIS, tislelizumab Data cut-off: August 10, 2020
Citation Format: Jie Wang, Zhiyong Ma, Dingzhi Huang, Yun Fan, Xinmin Yu, Sheng Hu, Ziping Wang, Zhihua Liu, Devrim Cabuk, Mahmut Gumus, Yiyuan Ma, Yan Wang, Yan Ma, Caicun Zhou. Tislelizumab (TIS) versus docetaxel (D) in patients with previously treated advanced squamous (sq) non-small-cell lung cancer (NSCLC): Sub-analysis from phase 3 RATIONALE-303 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 CT554.