Durvalumab Lengthens Survival in Extensive-Stage SCLC

Patients with extensive-stage small cell lung cancer (SCLC)—an aggressive disease with a poor prognosis—experienced an increase in median overall survival (OS) when treated with the PD-L1 inhibitor durvalumab (Imfinzi; AstraZeneca), according to interim results of the phase III CASPIAN trial. The findings, reported in The Lancet, could lead to a new treatment option for some with newly diagnosed disease.

Except for the PD-L1 inhibitor atezolizumab (Tecentriq; Genentech), which was approved earlier this year, the development of new SCLC treatments has been largely stagnant; for decades, the mainstay of treatment has been a combination of etoposide and platinum-based drugs. That's why durvalumab represents “a new treatment possibility for a subset of patients with limited possibilities for treatment and with clear unmet medical needs,” says lead investigator Luis Paz-Ares, MD, of the Hospital Universitario 12 de Octubre in Madrid, Spain.

In the randomized, controlled, open-label trial, researchers assigned 537 patients with untreated extensive-stage SCLC to receive either durvalumab plus etoposide–platinum chemotherapy or etoposide–platinum chemotherapy alone. Patients who received the checkpoint inhibitor had a median overall survival of 13 months compared with 10.3 months for those who received chemotherapy alone. At 18 months, 33.9% of patients treated with durvalumab were still alive, compared with 24.7% of those treated with the standard chemotherapy regimen.

The CASPIAN trial is not the only one to explore combining immunotherapy with chemotherapy for extensive-stage SCLC. Late last year, IMpower133 investigators reported that the phase III trial, which combined atezolizumab with chemotherapy, yielded a similar improvement in OS. However, there are key differences between the trials, Paz-Ares says. For example, CASPIAN allowed investigators to choose either cisplatin or carboplatin, whereas IMpower133 allowed only the use of carboplatin. Further research would be needed to make valid comparisons between atezolizumab and durvalumab in SCLC.

Complete results of the CASPIAN trial, which will include data from a third experimental arm assessing the durvalumab–chemotherapy combination plus the CTLA4 inhibitor tremelimumab (AstraZeneca), are yet to come. Mechanisms of resistance and biomarkers that predict response are active areas of research as well. At the ESMO Congress 2019, which ran from September 27 through October 1 in Barcelona, Spain, the CASPIAN team reported that PD-L1 expression did not appear to predict response.

CASPIAN and IMpower133 demonstrate the benefit of adding PD-L1 inhibitors to chemotherapy in extensive-stage SCLC, says CASPIAN investigator Enriqueta Felip, MD, of the Vall d’Hebron University Hospital in Barcelona, Spain. “However, the OS benefit is still modest,” Felip adds, highlighting the need for further research on which patients are most likely to benefit and how to best administer the new therapy, if approved. –Nicole Haloupek