KEY TAKEAWAYS
- The Phase III trial studied the efficacy of combining benmelstobart with anlotinib alongside the standard chemotherapy of etoposide/carboplatin (EC) for ES-SCLC. The focus was on comparing the outcomes between this combination and a placebo group.
- The combination of benmelstobart, anlotinib, and chemotherapy showed improved outcomes in ES-SCLC over standard chemotherapy.
This Phase III study, conducted across multiple centers, evaluated first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). Participants were divided into three groups: those receiving benmelstobart, anlotinib, or a placebo in the form of etoposide/carboplatin (EC). Chemotherapy remained the standard-of-care, with benmelstobart plus anlotinib, anlotinib, or placebo as maintenance therapy until disease progression or toxicity intolerance. The primary goals were overall survival (OS) and progression-free survival (PFS) in the intention-to-treat (ITT) population, assessed by an independent committee. The data from the benmelstobart+anlotinib+EC arm was compared to that of the placebo+EC arm.
Between March and December 2021, 738 patients (pts) from 72 centers in China participated. Of these, 246 pts were assigned to receive benmelstobart+anlotinib+EC while 247 pts were assigned to receive placebo+placebo+EC. As of the cutoff date (May 14, 2022), the median follow-up period was 14.0 months (range, 12.8 to 15.5). The study found that benmelstobart+anlotinib+EC provided significant benefits over placebo+EC in terms of median PFS (6.9 months vs. 4.2 months; hazard ratio (HR)=0.32; 95% CI, 0.26 to 0.41; P<0.0001), median OS (19.3 months vs. 11.9 months; HR=0.61; 95% CI, 0.47 to 0.79; P=0.0002), objective response (81.3% vs. 66.8%), and duration of response (5.8 months vs. 3.1 months). The study also reported that grade≥ 3 adverse events (AE) of any cause occurred in 232 (94.3%) pts in the benmelstobart+anlotinib+EC arm and 219 (89.0%) in the placebo+EC arm. The incidence of grade ≥3 treatment-related AEs (TRAEs) was 93.1% (229/246) versus 87.0% (214/246); and respectively 4.5% (11/246) vs 1.6% (4/246) were grade 5. The most common grade ≥3 TRAEs were decreased neutrophil count, platelet count, and white blood cell count in both arms. Any grade immune-related adverse events (irAEs) were noted in 105 pts (42.7%) in the benmelstobart+anlotinib+EC arm and 47 pts (19.1%) in the placebo+EC arm.
The combination of benmelstobart, anlotinib, and chemotherapy reached the historically longest OS in ES-SCLC, with a notable 7.4-month extension over standard chemotherapy. This treatment regimen also marked the first time a PFS exceeded 6 months. Additionally, the safety profile was deemed acceptable and manageable.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/1017
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04234607
Cheng, Y., Yang, R., Chen, J., Zhang, W., Xie, C., Hu, Q., Zhou, N., Huang, C., Wei, S., Sun, H., Li, X., Yu, Y., Lai, J., Yang, H., Fang, H., Chen, H., Zhang, P., Gu, K., Wang, Q., Shi, J., Yi, T., Xu, X., Ye, X., Wang, D., Xie, C., Liu, C., Zheng, Y., Lin, D., Zhuang, W., Lu, P., Yu, G., Li, J., Gu, Y., Li, B., Wu, R., Jiang, O., Wang, Z., Wu, G., Lin, H., Zhong, D., Xu, Y., Shu, Y., Wu, D., Chen, X., Wang, J., Wang, M. Benmelstobart with Anlotinib plus Chemotherapy as First-line Therapy for ES-SCLC: A Randomized, Double-blind, Phase III Trial.
