FDA OKs Durvalumab Combo for
Extensive-Stage SCLC

Nick Mulcahy

March 30, 2020

The US Food and Drug Administration has approved the immunotherapy durvalumab (Imfinzi, AstraZeneca) in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

Durvalumab plus chemotherapy "can be considered a new standard in ES-SCLC," said Myung-Ju Ahn, MD, Sungkyunkwan University, Seoul, South Korea, last year at the European Society of Medical Oncology (ESMO) annual meeting, where he discussed results from the phase 3 trial known as CASPIAN.

The new approval is based on efficacy and safety data from that trial, conducted in patients with previously untreated ES-SCLC. In the experimental group (n = 268), durvalumab plus etoposide and a platinum agent (EP) was followed by maintenance durvalumab, and in the control group (n = 269) patients received the EP regimen alone.

Median overall survival (OS) was 13 months in the durvalumab plus chemotherapy group compared with 10.3 months in the chemotherapy alone group (hazard ratio 0.73; 95% confidence interval [CI], 0.59 - 0.91; P = .0047).

Reporting these results, trial investigator Luis Paz-Ares, MD, Hospital Universitario 12 de Octubre, Madrid, Spain, put the new survival benefit in the context of standard treatments at the ESMO meeting last year.

"Initial response rates to etoposide plus a platinum are high, but responses are not durable and patients treated with EP typically relapse within 6 months of starting treatment with a median OS of approximately 10 months," he said.

In addition to the primary endpoint of OS, additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR).

Median PFS was not statistically significant with immunotherapy; it was 5.1 months (95% CI, 4.7 - 6.2) in the durvalumab plus chemotherapy group and 5.4 months (95% CI, 4.8 - 6.2) in the chemotherapy alone group (HR, 0.78; 95% CI, 0.65 - 0.94).

The investigator-assessed ORR was 68% in the durvalumab plus chemotherapy group and 58% in the chemotherapy alone group.

The most common adverse reactions (≥ 20%) in patients with ES-SCLC were nausea, fatigue/asthenia, and alopecia, according to the FDA.

At ESMO, Paz-Ares reported that rates of serious AEs were comparable at 30.9% and 36.1% for the durvalumab plus EP group vs EP alone, respectively; rates of AEs leading to discontinuation were identical in both groups at 9.4%. Unsurprisingly, immune-mediated AEs were higher at 19.6% in the durvalumab combination group vs 2.6% in the EP alone group.

In this setting, durvalumab is administered prior to chemotherapy on the same day. The recommended durvalumab dose (when administered with etoposide and carboplatin or cisplatin) is 1500 mg every 3 weeks prior to chemotherapy and then every 4 weeks as a single-agent maintenance therapy.

Durvalumab is already approved for unresectable, stage 3 non-small cell lung cancer (NSCLC) in patients whose disease has not progressed following concurrent chemotherapy and radiation therapy; it is also approved for use in urothelial cancer.

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