Abstract 1031P
Background
In RATIONALE-303 (NCT03358875), TIS significantly improved overall survival (OS) vs TAX in the intent-to-treat population (ITT) at the interim analysis (IA). TIS was later approved in China for advanced or metastatic NSCLC after progression on prior platinum-based chemotherapy. At the final analysis (FA), the co-primary endpoint of OS in the programmed death-ligand 1 (PD-L1, VENTANA SP263 assay) tumor cell ≥ 25% population was met, and TIS continued to improve OS compared with TAX in the ITT. Here we report FA results from the Asian vs non-Asian subgroups.
Methods
A total of 805 pts with histologically confirmed locally advanced or metastatic NSCLC that progressed during or following treatment with ≥ 1 platinum-based regimen were randomized 2:1 to receive TIS 200 mg or TAX 75 mg/m2 intravenously once every 3 weeks until disease progression, intolerable toxicity, or withdrawal of consent. Dual primary endpoints were OS in the ITT and PD-L1 ≥ 25% populations. Secondary endpoints included investigator-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety. A prespecified IA was conducted in ITT after ≈426 deaths (76% of planned events).
Results
In total, 643 Asian and 162 non-Asian pts were randomized. Baseline characteristics were balanced between treatment arms in both subgroups. Both subgroups demonstrated favorable OS, PFS, DoR, and ORR with TIS vs TAX (Table). Treatment-emergent adverse events (TEAEs) of ≥ Grade 3 with TIS vs TAX were experienced by 41.1% vs 75.2% of Asian pts and 45.9% vs 72.9% of non-Asian pts, respectively. Serious TEAEs with TIS vs TAX were experienced by 35.7% vs 31.4% of Asian pts and 29.7% vs 37.5% of non-Asian pts, respectively. Table: 1031P
| Asian | Non-Asian | |||
| ITT analysis set | TIS (n=424) | TAX (n=219) | TIS (n=111) | TAX (n=51) |
| Median study follow-up, months | 17.2 | 10.7 | 14.3 | 10.4 |
| Deaths, n (%) | 293 (69.1) | 169 (77.2) | 72 (64.9) | 37 (72.5) |
| mOS, months | 17.8 | 12.2 | 14.9 | 11.9 |
| HR* (95% CI) | 0.65 (0.54, 0.79); p < 0.0001 | 0.73 (0.48, 1.11); p=0.0674 | ||
| mPFS, months | 4.1 | 2.4 | 6.3 | 4.1 |
| HR* (95% CI) | 0.62 (0.51, 0.75); p < 0.0001 | 0.67 (0.45, 1.00); p=0.0241 | ||
| ORR, % | 21.5 | 5.9 | 27.0 | 11.8 |
| Odds ratio (95% CI) | 4.41 (2.41, 8.07); p < 0.0001 | 2.84 (1.12, 7.20); p=0.0226 | ||
| mDoR, months | 13.8 | 4.2 | 10.3 | 6.1 |
p values are descriptive. *Stratified by histology, lines of therapy, and PD-L1 expressionCI, confidence interval; HR, hazard ratio; m, median
Conclusions
In both Asian and non-Asian pts, TIS demonstrated favorable efficacy benefits compared with TAX and was generally well tolerated.
Clinical trial identification
NCT03358875.
Editorial acknowledgement
Medical writing support, under the direction of the authors, was provided by Arezou Seyed Hossein, MPharm, of Ashfield MedComms, an Ashfield Health company, and was funded by BeiGene, Ltd.
Legal entity responsible for the study
BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
C. Zhou: Financial Interests, Other, Honoraria: Lily China, Sanofi, BI, Roche, Qilu, MSD, Innovent Biologics, Hengrui, TopAlliance Biosciences Inc, Luye Pharma, C-Stone, Amoy Diagnostics, BeiGene; Financial Interests, Advisory Role: TopAlliance Biosciences Inc, Innovent Biologics, Hengrui. Y. Wang: Financial Interests, Full or part-time Employment: BeiGene (Beijing) Co., Ltd. S. Ghassemifar: Financial Interests, Full or part-time Employment: BeiGene. S. Li: Financial Interests, Full or part-time Employment: BeiGene, Ltd. G. Rivalland: Financial Interests, Invited Speaker: Astra-Zeneca; Roche; Financial Interests, Advisory Board: MSD-Asia-Pacific. All other authors have declared no conflicts of interest.