Updated results of the phase 3 CASPIAN clinical trial continue to show that durvalumab (Imfinzi) added to standard chemotherapy improves overall survival (OS) for patients with treatment-naïve extensive-stage small-cell lung cancer (ES-SCLC), according to a presentation at the ASCO 2020 virtual annual meeting.
“This [combination] is an effective first-line treatment in the extensive-stage setting, where improving outcomes has been a challenge, and so few patients survive 5 years,” said lead author Luis G. Paz-Ares, MD, PhD, Chair of the Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain.
“These results support the use of the PD-L1 inhibitor in combination with etoposide plus either cisplatin or carboplatin as a new front-line standard of care for this patient population,” Dr Paz-Ares added.
At a median follow-up of 25.1 months, the median OS was 12.9 months for patients who received durvalumab and chemotherapy with etoposide plus cisplatin or carboplatin versus 10.5 months (P = .0032) for those who received the chemotherapy regimen alone, translating to a 25% improvement. The OS data favored the addition of durvalumab to the chemotherapy regimen.
“The separation among the curves seems to be observed over time and, indeed, survival at 2 years improves from 14% in the control arm to 22% on the experimental arm. The magnitude of the benefit is very similar and very consistent across all the prespecified subgroups of patients analyzed, including those treated with cisplatin or those patients with liver or brain metastases,” Dr Paz-Ares said.
Approximately two-thirds of patients diagnosed with SCLC have extensive-stage disease, and approximately 80% of patients initially respond to chemotherapy, but the disease usually relapses within 6 months, with a median OS of approximately 10 months.
New FDA Indication
Based on interim findings from the CASPIAN study, in March 2020, the FDA approved durvalumab in combination with standard chemotherapy as first-line treatment for patients with ES-SCLC.
CASPIAN evaluated the impact of immunotherapy plus chemotherapy versus chemotherapy alone across 3 arms, including (1) durvalumab plus tremelimumab and etoposide plus either cisplatin or carboplatin every 3 weeks for 4 cycles, followed by durvalumab every 4 weeks until disease progression with an additional dose of tremelimumab (durvalumab plus tremelimumab arm); (2) durvalumab plus etoposide and cisplatin or carboplatin every 3 weeks for 4 cycles, followed by durvalumab every 4 weeks until disease progression (durvalumab plus chemotherapy); and (3) etoposide and cisplatin or carboplatin every 3 weeks for up to 6 cycles, followed by prophylactic cranial irradiation at the investigator’s discretion (chemotherapy-alone arm).
Overall, 805 patients were randomized to 1 of the 3 treatment arms. The OS was not significantly different for the first arm (durvalumab plus tremelimumab) versus etoposide and cisplatin or carboplatin alone and was therefore not the focus of Dr Paz-Ares’ presentation.
The percentage of patients with brain or central nervous system metastases was 10.4% in the durvalumab plus etoposide and cisplatin or carboplatin arm, and 10.0% in the chemotherapy-alone arm. Patients with liver metastases made up 40.3% and 38.7%, respectively.
In the updated analysis, the median progression-free survival for the durvalumab plus chemotherapy arm was 5.4 months versus 5.1 months for the chemotherapy-alone arm. The objective response rate was 67.9% for the immunotherapy plus chemotherapy arm compared with 58.0% for chemotherapy alone (odds ratio, 1.53; 95% confidence interval, 1.08-2.18). The median duration of response was the same (5.1 months) for both arms.
“These data reinforce durvalumab plus chemotherapy as an important new standard of care for extensive-stage small-cell lung cancer patients, and this regimen offers patients convenient dosing every 4 weeks during maintenance,” said José Baselga, MD, PhD, Executive Vice President of Research & Development, Oncology, AstraZeneca.
The safety was consistent with the known adverse events associated with the agents used in each regimen. The rates of grade 3 or 4 and serious adverse events were, respectively, 62.3% and 32.1% in the durvalumab plus chemotherapy arm, and 62.8% and 36.5% in the chemotherapy-alone group.
Adverse events leading to treatment discontinuation occurred in 10.2% in the durvalumab plus chemotherapy group, and 9.4% in the chemotherapy-alone cohort. There were 6 deaths in the durvalumab plus chemotherapy arm, and 2 in the chemotherapy-alone arm that investigators attributed to treatment-related adverse events.