First-line serplulimab + chemo ups survival in extensive-stage SCLC

The addition of serplulimab to chemotherapy in the first-line setting improved overall survival (OS) in patients with extensive-stage small cell lung cancer (SCLC), according to results of the ASTRUM-005 trial.

“To our knowledge, this is the first phase III trial demonstrating OS benefits of a PD-1 inhibitor in combination with chemotherapy as a first-line treatment for patients with extensive-stage SCLC,” said the investigators.

Participants in this international (114 centres in six countries), double-blind trial were 585 adults (mean age 61.1 years, 17.8 percent female) with extensive-stage* SCLC and ECOG performance score 0–1 with no prior exposure to systemic treatment. They were randomized 2:1 to receive intravenous (IV) serplulimab (4.5 mg/kg; n=389) or placebo (n=196) Q3W in addition to IV carboplatin (area under the curve 5 mg/mL/min on day 1) and etoposide (100 mg/m² on days 1, 2, and 3) Q3W for ≤12 weeks.

About two-thirds of the population was Asian. Forty-two percent of patients (n=246) completed the study, while 79.5 percent (n=465) discontinued treatment (primarily due to disease progression). At data cut-off, 24.9 and 11.7 percent of patients in the serplulimab and placebo groups, respectively (n=97 and 23, respectively), remained on treatment. Forty-four and 43 percent, respectively, received subsequent treatment after disease progression.

At a median 12.3 months follow-up, OS was significantly improved among patients in the serplulimab than placebo group (median 15.4 vs 10.9 months; hazard ratio [HR], 0.63, 95 percent confidence interval [CI], 0.49–0.82; p<0.001), with estimated 2-year OS rates of 43.1 percent vs 7.9 percent. [JAMA 2022;328:1223-1232]

The OS benefit with serplulimab over placebo was consistent across prespecified subgroups.

Progression-free survival (PFS), assessed by an independent radiology review committee, favoured serplulimab over placebo (median 5.7 vs 4.3 months; HR, 0.48, 95 percent CI, 0.38–0.59). Objective response rates were 80.2 and 70.4 percent in the serplulimab and placebo groups, respectively. Among patients with complete or partial response, duration of response was a median 5.6 and 3.2 months in the serplulimab and placebo groups, respectively, with 24.0 and 8.9 percent, respectively, having a response that lasted ≥12 months.

Patients in the serplulimab and placebo groups were exposed to treatment for a median 22.0 and 16.4 weeks, respectively. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 82.5 and 80.1 percent, respectively. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 33.2 and 27.6 percent, respectively, the most common being decreased neutrophil count (14.1 percent vs 13.8 percent), decreased white blood cell count (8.5 percent vs 8.7 percent), decreased platelet count (6.2 percent vs 8.2 percent), and anaemia (5.4 percent vs 5.6 percent).

TEAE-related discontinuation rate was comparable between groups (8.0 percent vs 7.7 percent), while TRAE-related discontinuation occurred in 4.9 percent vs 4.1 percent. TEAE-related deaths occurred in 7.7 percent vs 10.2 percent. Three patients died of AEs attributed to serplulimab (acute coronary syndrome, pyrexia, and decreased platelet count), while one died of an AE attributed to placebo (thrombocytopenia). All four TRAE-related deaths were immune related.

Grade ≥3 immune-related AEs occurred in 9.5 and 5.6 percent of serplulimab and placebo recipients, respectively. The most common immune-related AEs (≥5 percent) were hypo- and hyperthyroidism. About 8 percent of each group experienced pneumonia, with four and two cases in the serplulimab and placebo groups, respectively, grade ≥3.

“AEs attributed to serplulimab reflect the toxic effects frequently observed with immunotherapy in patients with SCLC,” the investigators noted. “Pneumonia occurred at a frequency similar to other PD-1 and PD-L1 inhibitors.”

The short follow-up period, the sole use of carboplatin as the platinum chemotherapy agent, and the non-use of durvalumab or atezolizumab plus chemotherapy (standard treatment for this disease in this setting) as comparators were limitations. The 20 percent of patients who were never-smokers, higher than that in other trials with a greater proportion of non-Asian patients, is also a limitation.

“[All-in-all, the results support] the use of serplulimab plus chemotherapy as the first-line treatment for this patient population,” the investigators concluded.

*no active central nervous system metastases (asymptomatic and stable metastases allowed)