KEY TAKEAWAYS
- The phase 3 RATIONALE-312 trial assessed the efficacy and safety of tislelizumab + chemotherapy vs placebo + chemotherapy regimen for first-line treatment in ES-SCLC patients.
- The study’s primary goal was OS, and secondary endpoints were investigator-assessed PFS, ORR, and DoR.
- Tislelizumab with chemotherapy showed significant therapeutic benefits and acceptable safety in untreated ES-SCLC patients compared to a placebo and chemotherapy.
The RATIONALE-312 phase 3 study enrolled eligible patients (pts) in China with previously untreated extensive-stage small-cell lung cancer (ES-SCLC). Patients were randomized in a 1:1 ratio to undergo four cycles of either 200 mg of tislelizumab or a placebo in conjunction with either etoposide plus carboplatin or cisplatin administered intravenously every three weeks. After these cycles, either tislelizumab or a placebo was given as maintenance therapy until either the disease advanced, clinical benefits were lost, unacceptable toxicity occurred, or consent was withdrawn.
The main endpoint was overall survival (OS) in an intent-to-treat analysis set, while key secondary outcomes were progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR) according to RECIST v1.1 criteria, as well as safety metrics.
From July 22, 2019, to April 22, 2021, 457 pts were allocated to the study—227 to the tislelizumab group and 230 to the placebo group. Both groups were broadly similar in terms of baseline demographic features. However, the tislelizumab group showed a higher initial tumor burden; more participants had advanced disease (AJCC Stage IV: 91.2% vs 87.4%) and at least three metastatic lesions (80.6% vs 71.3%).
As of the final data review on April 19, 2023, the median study follow-up duration was 14.2 months (ranging from 0.1 to 44.9 months). The combination of tislelizumab and chemotherapy yielded a significantly better overall survival (OS) rate than the placebo plus chemotherapy (stratified HR=0.75 [95% CI: 0.61, 0.92]; P=0.0035; median OS: 15.5 months vs 13.5 months). One-, two-, and three-year OS rates were 62.7%, 33.2%, and 25.0% for the tislelizumab group and 58.4%, 22.4%, and 9.3% for the placebo group.
Tislelizumab significantly enhanced progression-free survival (PFS) (stratified HR=0.63; P<0.0001; median PFS: 4.8 vs 4.3 months). It also resulted in a higher confirmed objective response rate (ORR) (68.3% vs 61.7%) and longer duration of response (DoR) (4.3 vs 3.7 months). Subsequent systemic anticancer treatments were given to 59.9% of tislelizumab pts and 73.9% of placebo pts. In terms of safety, ≥grade 3 treatment-related treatment-emergent adverse events (TRAEs) were seen in 85.5% of the tislelizumab group and 86.0% of the placebo group, with hematologic toxicity being the most frequent in both. Serious TRAEs were more common in the tislelizumab group (31.3% vs 17.9%), as were immune-mediated adverse events (imAEs) (38.3% vs 17.9%). Most imAEs were controllable through systemic steroids or hormone treatments.
Tislelizumab and chemotherapy as first-line treatment for untreated ES-SCLC pts showed significant clinical benefit and manageable safety than placebo and chemotherapy.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/2744
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04005716
Cheng, Y., Fan, Y., Zhao, Y., Huang, D., Li, X., Zhang, P., Kang, M., Yang, N., Zhong, D., Wang, Z., Yu, Y., Zhang, Y., Zhao, J., Qin, T., Chen, C., Leaw, S., Zheng, W., Song, Y. First-Line Chemotherapy With or Without Tislelizumab for Extensive-Stage Small Cell Lung Cancer: RATIONALE-312 Phase 3 Study.
