GENEVA, SWITZERLAND-Few grade 3 or higher immune-related adverse events were observed with first-line durvalumab plus platinum-etoposide in patients with extensive-stage small cell lung cancer (ES-SCLC), according to findings from the safety analysis of the phase III CASPIAN study presented at the 2019 ESMO Immuno-Oncology Congress.

Mustafa Ozguroglu, MD, Professor of Medical Oncology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa in Turkey, presented results from analyses of safety, pharmacokinetics (PK), and immunogenicity from the open-label phase III CASPIAN (NCT03043872) study of first-line durvalumab plus platinum-etoposide (EP) compared to EP alone in patients with ES-SCLC.

Findings from the pre-planned interim analysis showed that durvalumab plus EP significantly improved overall survival (OS) as compared to EP alone in patients with ES-SCLC (HR 0.73; 95% CI, 0.59-0.91; p = 0.0047).

The rates of all-cause adverse events (AEs) as well as AEs leading to discontinuation were similar with both treatments, although serious AEs (SAEs) were numerically lower at 30.9 percent versus 36.1 percent, respectively, and immune-mediated AEs (imAEs) were higher with the addition of durvalumab to EP, prompting Ozguroglu and co-investigators to further evaluate safety, PK, and immunogenicity, the study's secondary endpoints.

CASPIAN enrolled treatment-naive patients with ES-SCLC and WHO performance status 0/1 that were randomized to treatment with EP plus durvalumab at 1,500 mg every 3 weeks, or EP plus durvalumab at 1,500 mg plus tremelimumab at 75 mg every 3 weeks, or to receive EP every 3 weeks. Investigator's choice of carboplatin or cisplatin was allowed. In the immunotherapy arm, patients were treated with 4 cycles of EP, followed by 1500 mg durvalumab every 4 weeks until progression; up to 6 cycles of EP and optional prophylactic cranial irradiation were permitted in the control EP arm.

At the event, results from the 265 patients who were treated with durvalumab plus EP and the 266 control patients receiving EP were presented. The PK analysis showed that serum concentrations of durvalumab were within the expected range. PK profiles of EP components were similar across both arms. In the durvalumab/EP arm, 201 patients were evaluated for anti-drug antibodies (ADA); of these, 11 (5.5%) were positive for ADA to durvalumab at baseline only, and no patients were positive for treatment-emergent ADA or neutralising antibodies.

Any imAEs occurred in 52 (20%) patients on durvalumab/EP versus seven (3%) of patients on EP; of these, 5 percent versus 1 percent were grade >=3, respectively. The most commonly reported any grade imAEs with durvalumab/EP were hypothyroid (9%), hyperthyroid (5%), pneumonitis (3%), hepatic (3%), and 2 percent of patients each had dermatitis/rash, diarrhoea/colitis, thyroiditis, and type 1 diabetes. Grade >=3 imAEs with durvalumab plus EP included pneumonitis (1%), hepatic (2%), diarrhea/colitis (0.4%), and type 1 diabetes (2%). The earliest any grade imAE was diarrhea/colitis, which was seen at median 28 days after receiving the first dose.

With EP alone, commonly reported any grade imAEs included hypothyroid (1%), pneumonitis (1%), and diarrhoea/colitis (0.4%); of these only Grade >=3 pneumonitis (1%) was recorded. The first imAEs of dermatitis/rash occurred at a median 31 days.

The authors pointed out that the incidence of anti-drug antibodies to durvalumab was low and were seen only at baseline. They further remarked that the safety profile of durvalumab/EP was consistent with previous reports of both durvalumab and EP.