Abstract CT552: RATIONALE 304: Tislelizumab (TIS) plus chemotherapy versus chemotherapy alone as first-line (1L) treatment for non-squamous (non-sq) NSCLC in patients (pts) aged 65-75 years
Authors: Lu Shun , Wang Jie , Yu Yan , Yu Xinmin , Hu Yanping , Ma Zhiyong , Li Xingya , Zhuang Wu , Liu Yunpeng , Li Weidong , Cui Jiuwei , Wang Dong , Liao Wangjun , Wang Mengzhao , Zhou Jianying , Wang Zhehai , Sun Yuping , He Wanyu , Bao Yuanyuan 
Published: June 2022

Background: Primary results from the Phase 3 RATIONALE-304 study (NCT03663205) showed efficacy and a manageable safety/tolerability profile for TIS, an anti-programmed cell protein 1 monoclonal antibody, plus chemotherapy, as 1L treatment for non-sq NSCLC. We report results from pts aged 65-75 years.

Methods: In RATIONALE-304, eligible pts (18-75 years) were treatment-naïve and had locally advanced or metastatic non-sq NSCLC. Pts were stratified by disease stage and programmed death-ligand 1 expression, and randomized 2:1 to receive TIS (200 mg intravenously [IV]) plus platinum (carboplatin AUC 5 or cisplatin 75 mg/m2 IV) plus pemetrexed 500 mg/m2 every three weeks for 4-6 cycles followed by maintenance TIS plus pemetrexed (Arm A), or platinum pemetrexed for 4-6 cycles followed by maintenance pemetrexed (Arm B). Progression-free survival (PFS) by independent review committee (IRC), objective response rate (ORR), and safety were assessed in pts aged 65-75 years.

Results: In total, 97 pts aged 65-75 years were randomized to Arm A (60 pts) or Arm B (37 pts). The median age of pts was 68.0 years, and 76 pts (78.4%) were male. PFS was longer, and ORR higher, in Arm A vs Arm B (Table). Overall, 59 pts in Arm A, and 37 pts in Arm B experienced ≥ 1 treatment-emergent adverse event (TEAE). In Arm A, Grade ≥ 3 TEAEs occurred in 43 (72.9%) pts aged 65-75 years vs 150 (67.6%) aged ≥ 18 years, and in Arm B, 18 (48.6%) pts aged 65-75 years vs 59 (53.6%) pts aged ≥ 18 years. TEAEs leading to permanent discontinuation of any component of study treatment occurred in 19 (32.2%) pts in Arm A, and 5 (13.5%) pts in Arm B. 21 (35.6%) pts receiving TIS experienced ≥ 1 immune-related TEAE.

Conclusions: Observed improvements in PFS and ORR support the treatment benefits of TIS in combination with platinum and pemetrexed chemotherapy in pts aged 65-75 with advanced non-squamous NSCLC. The safety profile of TIS in pts aged 65-75 years was similar to the safety profile for all pts in the overall study population.

Table Arm A (N=60) Arm B (N=37) PFS Events (%) 27 (45.0) 20 (54.1) HR (95% CI) 0.727 (0.407, 1.297) - Median, months (95% CI) 9.7 (5.75, 11.53) 7.7 (4.21, 9.76) ORR, % (95% CI) 53.3 (40.0, 66.3) 40.5 (24.8, 57.9) HR, hazard ratio

Citation Format: Shun Lu, Jie Wang, Yan Yu, Xinmin Yu, Yanping Hu, Zhiyong Ma, Xingya Li, Wu Zhuang, Yunpeng Liu, Weidong Li, Jiuwei Cui, Dong Wang, Wangjun Liao, Mengzhao Wang, Jianying Zhou, Zhehai Wang, Yuping Sun, Wanyu He, Yuanyuan Bao. RATIONALE 304: Tislelizumab (TIS) plus chemotherapy versus chemotherapy alone as first-line (1L) treatment for non-squamous (non-sq) NSCLC in patients (pts) aged 65-75 years [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 CT552.