medwireNews: Adding the PD-L1 inhibitor adebrelimab to first-line chemotherapy significantly extends overall survival (OS) for patients with extensive-stage small-cell lung cancer (ES-SCLC), Chinese investigators report.
After a median 13.5 months of follow-up, the phase 3 CAPSTONE-1 trial achieved a 2.5-month improvement in OS with the use of adebrelimab 20 mg/kg on day 1 of each 21-day cycle versus placebo when given alongside four to six cycles of carboplatin and etoposide, say Ying Cheng (Jilin Cancer Hospital, Changchun) and co-authors.
“These findings, along with an acceptable safety profile, support adebrelimab plus chemotherapy as a new first-line treatment option for ES-SCLC,” they write in The Lancet Oncology.
However, the authors observe that as the study was conducted exclusively in Chinese sites, both efficacy and safety “remain to be confirmed” in patients of other ethnicities.
The median OS duration was 15.3 months for the 230 patients randomly assigned to receive adebrelimab versus 12.8 months for the 232 instead given placebo, with a hazard ratio (HR) for death of 0.72. The OS rate was higher with adebrelimab than placebo at 12 months (62.9 vs 52.0%) and 24 months (31.3 vs 17.2%), and further analysis using a cutoff of 28.6 months (the minimum of the longest follow-up time for any participant) gave a restricted mean survival time of 16.8 months with adebrelimab versus 14.5 months with placebo.
The researchers emphasize that the OS benefit associated with the PD-L1 inhibitor regimen “was sustained” despite patients given adebrelimab being less likely than controls to have received at least one subsequent systemic therapy after discontinuing their study treatment (59 vs 70%).
Median progression-free survival (PFS) was also significantly longer with adebrelimab than placebo, at 5.8 versus 5.6 months and a HR of 0.67. The PFS rate was higher with the PD-L1 inhibitor after 6 months (49.4 vs 37.3%) and 12 months (19.7 vs 5.9%).
In addition, adebrelimab-treated patients were more likely to achieve an objective response than controls (70.4 vs 65.9%) and had a longer median duration of response to treatment (5.6 vs 4.6 months). At 12 months, 20.0% of patients given adebrelimab had an ongoing response compared with 4.0% of the placebo-treated patients.
Cheng et al note that the median duration of treatment was 27.4 weeks with adebrelimab and 25.2 weeks with placebo, and patients in both arms received a median six cycles of chemotherapy.
Grade 3 or more severe treatment-related adverse events (AEs) occurred in 86% of patients given adebrelimab and 85% of controls, with hematologic AEs the predominant side effects, such as decreases in neutrophils (76 vs 75%), white blood cells (46 vs 38%), and platelets (38 vs 34%), and anemia (28 vs 28%).
Two fatal AEs possibly linked to treatment occurred in the adebrelimab arm (respiratory failure and interstitial lung disease or pneumonia) and two occurred in the placebo arm (multisystem organ failure and unknown cause of death).
In addition, grade 3 or more severe immune-mediated AEs were reported for 5% of adebrelimab-treated patients and 3% of placebo-treated controls, with hepatic laboratory abnormalities and pneumonitis the most common issues with adebrelimab.
Writing in a linked comment, Katherine Smith and Aaron Mansfield, both from Mayo Clinic in Rochester, Minnesota, USA, say that despite the OS benefit with adebrelimab plus chemotherapy in ES-SCLC, “it is not certain how widely available adebrelimab will be for this indication, or how previous approvals will affect its adoption.”
They point out the higher rate of grade 3–4 neutropenia in the experimental arm of CAPSTONE-1 compared with the IMpower133 trial of atezolizumab and the CASPIAN trial of durvalumab (76 vs 23 and 24%, respectively) for ES-SCLC, and suggest this may be due to the greater number of chemotherapy cycles with the adebrelimab regimen.
“When balancing the observed survival outcomes with adverse events across [the three trials], it appears that four cycles of triplet induction therapy might suffice,” the commentators write.
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Lancet Oncol; doi: 10.1016/S1470-2045(22)00224-8
Lancet Oncol; doi: 10.1016/S1470-2045(22)00288-1