Durvalumab added to etoposide improves outcomes in ES-SCLC

A planned interim analysis of the CASPIAN study, in which durvalumab ± tremelimumab combined with etoposide as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC) is assessed, showed that adding durvalumab significantly improved overall survival (OS) compared to a treatment with up to 6 cycles of etoposide and prophylactic cranial irradiation (PCI).

In this trial, a total of 537 patients with previously untreated ES-SCLC and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0/1 were randomised (1:1:1) to durvalumab 1,500 mg + etoposide q3w; durvalumab 1,500 mg + tremelimumab 75 mg + etoposide q3w; or etoposide q3w. Patients in immunotherapy arms received up to 4 cycles of etoposide followed by maintenance durvalumab until progression. Patients in the etoposide arm received up to 6 cycles of etoposide and PCI (at the investigator’s discretion). Investigator’s choice of cisplatin or carboplatin was allowed across all arms and was a stratification factor at randomisation. The primary endpoint was OS and the data cut-off was 11 March 2019.

The results showed that 56.8% of patients received 6 cycles of etoposide. The addition of durvalumab to etoposide resulted in significantly improved OS compared to etoposide, with 33.9 of patients in the durvalumab + etoposide arm still alive at 18 months vs 24.7% in the etoposide arm [1]. Median OS was 13 months vs 10.3 months, respectively (HR 0.73; 95% CI 0.591-0.909; P=0.0047). Median progression-free survival (PFS) was 5.1 vs 5.4 months, respectively (HR 0.78; 95% CI 0.645-0.936); the 12-month PFS rate was 17.5% vs 4.7%, respectively. Mean duration of response was 5.1 months vs 5.1 and the objective response rate (ORR) was 67.9 vs 57.6, respectively (OR 1.56; 95% CI 1.095-2.218).

The incidences of grade 3/4 adverse events and adverse events leading to discontinuation were similar between arms; the incidence of haematological toxicities was numerically higher in the etoposide arm. It needs to be noted that this chemo-immunotherapy regimen offers flexibility in platinum choice (carboplatin or cisplatin), reflecting current clinical practice for this challenging disease. Thus, combining durvalumab with either cisplatin- or carboplatin-etoposide in ES-SCLC provides an important new treatment option for patients and physicians.

Editor note: This study correlates well in its outcome with IMPOWER 133 (comparing standard carboplatine/etoposide with or without additional atezolizumab), showing a significant survival benefit in the first-line treatment of metastatic SCLC patients. The fact that this is the first meaningful advance in the systemic treatment of mSCLC in this century gives these results even more importance.

1.  Paz-Ares L, et al. PL02.11. WCLC 2019.

Posted on 8 November, 201925 March, 2024