Extending Survival in Extensive-Stage Small-Cell Lung Cancer

Adding the immunotherapy agent durvalumab to chemotherapy improves overall survival in patients with extensive-stage small-cell lung cancer (ES-SCLC), according to the results of the CASPIAN trial. Findings were presented at the International Association for the Study of Lung Cancer (IASLC) 2019 World Conference on Lung Cancer (WCLC) held in Barcelona.

In this phase III trial, investigators assessed the clinical efficacy and safety of durvalumab with or without tremelimumab with etoposide and carboplatin or cisplatin (EP) chemotherapy followed by durvalumab with or without tremelimumab maintenance therapy compared with EP alone as first-line treatment in ES-SCLC.

“The addition of durvalumab to EP as first-line treatment for extensive-stage non-small cell lung cancer significantly improved overall survival (27% reduction in risk of death) versus a robust control arm that permitted up to 6 cycles of etoposide,” noted lead study author Luis Paz-Ares, MD, of the Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense and Ciberonc in Madrid.

A total of 537 previously untreated ES-SCLC patients were randomly assigned to receive 1) durvalumab with 4 courses of EP chemotherapy, 2) durvalumab with tremelimumab and EP for 4 cycles, or 3) EP alone for as many as 6 cycles. Data presented at WCLC 2019 compared the durvalamab arm to a control.

Paz-Ares and colleagues found that 53.7% of patients given immunotherapy were alive at 12 months vs 39.8% of those in the control group. At 18 months, these measures were 33.9% vs 24.7%, respectively. Furthermore, patients in the durvalumab group had a median overall survival of 13 months compared with 10.3 months in the EP control group (hazard ratio [HR], 0.73; 95% CI: 0.591–0.909; P = .0047). Clinical benefits were also supported by the progression-free survival and objective response rates in these patients.

“Of note, this chemo-immunotherapy regimen offers flexibility in platinum choice (carboplatin or cisplatin), reflecting current clinical practice for this challenging disease,” added Paz-Ares.

Safety in the study aligned with known safety profiles of the agents used. “In terms of safety, we didn’t identify any new safety signals,” said Paz-Ares. “For most of the cases, toxicity profile was similar among the two study arms, [with the] same number of grade 3–4 events [and] serious adverse events in the two treatment arms. The main difference was in the incidence of immune-mediated events, as anticipated.”

Specifically, in the durvalumab plus EP arm (n = 265), the frequency of grade 3–4 adverse events was 61.5% vs 62.4% in the EP arm. Serious adverse events occurred in 30.9% of patients in the durvalumab plus EP arm vs 36.1% in the EP arm (n = 266). Immune-mediated adverse events occurred in 19.6% of those in the durvalumab plus EP arm vs 2.6% of those in the EP arm.

Of note, ES-SCLC typically carries a poor prognosis, with a mean survival time of 10 months following diagnosis. For more than 30 years, the first-line treatment for ES-SCLC entailed EP with few other options.

Although the initial response rates observed in this study were high, they were not durable, with patients typically relapsing at 6 months. As a first-line treatment, immune checkpoint blockade has demonstrated clinical efficacy in ES-SCLC patients.

“Very importantly, the benefit was seen across all groups, including those [patients] with brain metastases,” concluded Paz-Ares. “Combining durvalumab with either cisplatin- or carboplatin-etoposide in ES-SCLC provides an important new treatment option for patients and physicians.”

James L Mulshine, MD, of Rush University in Chicago, who was not involved in the study, told Cancer Network that the new results could be important.

“This is welcome news in a challenging clinical setting, especially since the addition of blocking PD-L1 in this setting is not associated with significantly great side-effect profile,” he said. “This is an important early signal that merits very close follow-up.”