Frontline Durvalumab/Chemo Combo Improves OS in Extensive-Stage SCLC

Jose Baselga, MD

José Baselga, MD

Durvalumab (Imfinzi) combined with standard etoposide and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with standard chemotherapy alone as a first-line treatment in patients with extensive-stage small cell lung cancer (SCLC), meeting the primary endpoint of the phase III CASPIAN trial (NCT03043872).

The safety and tolerability findings of the immunotherapy/chemotherapy combination were consistent with the safety profile of each agent alone, stated AstraZeneca, the developer of durvalumab, in a press release. The full findings of the study will be presented at an upcoming medical meeting.

“The phase III CASPIAN results offer new hope for patients who are facing the devastating diagnosis of small cell lung cancer, and for whom new medicines are urgently needed,” José Baselga, executive vice president, Oncology R&D, AstraZeneca, stated in the press release. “This is the first trial offering the flexibility of combining immunotherapy with different platinum-based regimens in small cell lung cancer, expanding treatment options.”

In the international, multicenter, open-label, phase III CASPIAN study, investigators randomized 988 treatment-naïve patients with extensive-stage SCLC 1:1:1 to durvalumab plus etoposide and either cisplatin or carboplatin, durvalumab plus the CTLA-4 inhibitor tremelimumab and chemotherapy, or chemotherapy alone. In both experimental arms, patients received ≤4 cycles of chemotherapy, while the control arm permitted ≤6 cycles of chemotherapy and prophylactic cranial irradiation.

In the durvalumab arms, the PD-L1 inhibitor is given intravenously every 3 weeks for four 12-week cycles, and every 4 weeks thereafter until progressive disease or treatment discontinuation. In the durvalumab/tremelimumab arm, the CTLA-4 inhibitor is given IV every 3 weeks for four 12-week cycles, and an additional dose is given in week 16.

Those enrolled on the trial were adult patients aged ≥18 years with histologically or cytologically documented stage IV extensive-stage SCLC, based on the American Joint Committee on Cancer Stage 7th edition. Patients must also have a World Health Organization/ECOG performance status of 0 or 1.

Patients who had a history of radiation to the chest prior to systemic therapy or had planned consolidation chest radiation therapy; paraneoplastic syndrome of autoimmune nature; active infection with tuberculosis, HIV, hepatitis B and C; active or prior autoimmune or inflammatory disorders; or uncontrolled intercurrent illness were excluded from enrollment.

The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), overall response rate, 6- and 12-month PFS rates, 18-month OS rate, quality of life, pharmacokinetics, and pharmacodynamics. Safety was also assessed as another outcome measure.

Patients were assessed at time of screening as a baseline, with follow-ups at week 6 ±1 week from the date of randomization, at week 12 ±1 week from the date of randomization, and then every 8 weeks ±1 week until disease progression. The safety and tolerability of the dosing and schedule from the experimental arms are reviewed via an Independent Data Monitoring Committee at two early stages of enrollment.

CASPIAN, which is no longer recruiting, is being conducted in more than 200 institutions across 22 countries. Durvalumab is also being explored in the phase III ADRIATIC trial (NCT03703297), which is looking at the PD-L1 inhibitor alone or in combination with tremelimumab following concurrent chemoradiation therapy in patients with limited-stage SCLC.

Durvalumab is currently approved by the FDA for the treatment of patients with locally advanced, unresectable stage III non—small cell lung cancer who have not progressed following chemoradiotherapy.

Imfinzi Improves Overall Survival at Interim Analysis in the Phase III CASPIAN Trial in 1st-Line Extensive-Stage Small Cell Lung Cancer. AstraZeneca. Published June 27, 2019. https://bit.ly/2RFpKlz. Accessed June 27, 2019.