medwireNews: The addition of the anti-PD-1 agent serplulimab to chemotherapy significantly boosts the overall survival (OS) of treatment-naïve individuals with extensive-stage small-cell lung cancer (SCLC), according to ASTRUM-005 trial results published in JAMA.
“To our knowledge, this is the first phase 3 trial demonstrating overall survival benefits of a PD-1 inhibitor in combination with chemotherapy as a first-line treatment for patients with extensive-stage SCLC,” writes the team led by Ying Cheng, from Jilin Cancer Hospital in Changchun, China.
They add that the secondary efficacy outcomes, such as progression-free survival (PFS), also favored serplulimab, pointing to the benefit of the combination in this setting.
The authors of a related editorial say that “[h]ad there not been 2 prior RCTs [randomized controlled trials], demonstrating benefit with 2 other immune checkpoint inhibitors, this trial would have been practice changing.”
Noura Choudhury and Gregory Riely, both from Memorial Sloan Kettering Cancer Center in New York, USA, draw attention to some of the limitations of the trial, such as the lack of an optimal control, “discordance from the population of US patients with SCLC” with regard to race and ethnicity, and the high proportion of nonsmokers in the study.
And they say: “Although the ASTRUM-005 trial provides new data that demonstrate the potential benefit of serplulimab combined with chemotherapy for treatment of patients with extensive-stage SCLC, the findings serve primarily to confirm concepts demonstrated in other RCTs and, considering the study limitations, the precise role of this PD-1 antibody remains to be determined.”
The editorialists suggest that there could be an advantage to adding a third immune checkpoint inhibitor (after durvalumab and atezolizumab) to the treatment armamentarium “if serplulimab could be offered to patients at a lower cost, but that is not known currently, and such price differences have not been observed with prior approvals of drugs entering the US market with similar mechanisms to previously approved products.”
In the double-blind study conducted in China, Georgia, Poland, Russia, Turkey, and Ukraine, 585 patients who had not received prior systemic therapy for extensive-stage SCLC were randomly allocated to receive either intravenous serplulimab 4.5 mg/kg or placebo every 3 weeks until unacceptable toxicity, disease progression, or death, alongside up to four 3-weekly cycles of etoposide 100 mg/m2 given on days 1–3 plus carboplatin AUC 5 on day 1.
After a median follow-up of 12.3 months, the primary endpoint of OS was significantly prolonged for the 389 participants who received serplulimab plus chemotherapy relative to their 196 counterparts instead given placebo plus chemotherapy, at a median of 15.4 versus 10.9 months, and a hazard ratio for death of 0.63 in favor of the PD-1 inhibitor.
The estimated 1-year OS rates in the serplulimab and placebo groups were 60.7% and 47.8%, respectively, while the corresponding 2-year rates were 43.1% and 7.9%.
Median PFS as assessed by independent review was significantly longer in the serplulimab than placebo group, at 5.7 versus 4.3 months, and the independently evaluated objective response rate was higher and the median duration of response was longer, at 80.2% versus 70.4% and 5.6 versus 3.2 months, respectively.
Cheng and colleagues report that grade 3 or more severe treatment-related adverse events (TRAEs) occurred in 33.2% of serplulimab-treated patients and 27.6% of those given placebo, with the most common events being decreased neutrophil (14.1 vs 13.8%) and white blood cell (8.5 vs 8.7%) count.
TRAEs led to treatment discontinuation in a comparable 4.9% and 4.1% of patients in the serplulimab and placebo groups, respectively, while there were three fatal TRAEs with serplulimab (one case each of acute coronary syndrome, pyrexia, and decreased platelet count) and one with placebo (thrombocytopenia).
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