Frontline durvalumab led to a statistically significant and clinically meaningful improvement in overall survival (OS) in combination with etoposide and platinum-based chemotherapy in patients with extensive-stage small cell lung cancer, according to the results of a planned interim analysis of the phase III CASPIAN trial.
Jose Baselga, MD, PhD
Frontline durvalumab (Imfinzi) led to a statistically significant and clinically meaningful improvement in overall survival (OS) in combination with etoposide and platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (SCLC), according to the results of a planned interim analysis of the phase III CASPIAN trial.
In an announcement of the positive topline results, AstraZeneca, the company developing durvalumab, also said that the toxicity of the combination was in line with the known safety profiles for each agent. Further findings from the CASPIAN trial will be submitted for presentation 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, MD, PhD, executive vice president of oncology research and development, AstraZeneca, said in a statement. “This is the first trial offering the flexibility of combining immunotherapy with different platinum-based regimens in small-cell lung cancer, expanding treatment options.”
The CASPIAN trial is a randomized, open-label, multicenter, global phase III study with 3-arms looking at durvalumab in patients with previously untreated extensive-stage SCLC (NCT03043872). The trial is being conducted in more than 200 centers across 22 countries.
Patients in the trial were randomized 1:1:1 to receive either durvalumab and tremelimumab with carboplatin or cisplatin plus etoposide, durvalumab and platinum-based chemotherapy plus etoposide, or etoposide and platinum-based chemotherapy alone.
In the first and second arm, treatment is given until disease progression, and in the third arm, platinum chemotherapy and etoposide is given for 6 cycles with the addition of prophylactic cranial irradiation at the investigators’ discretion if needed.
The trial was open to adult patients with extensive disease who were eligible to receive a platinum-based chemotherapy and had an ECOG performance status of 0 or 1.
The primary endpoint of the CASPIAN trial is OS and secondary endpoints include progression-free survival (PFS), objective response rate, the PFS rate at 6 months and 12 months, and the OS rate at 18 months. The investigators are also looking to quality-of-life measurements, safety, and pharmacokinetics. Study investigators have also designated PFS after subsequent anticancer therapy and biomarker correlation with response to treatment as exploratory endpoints.
AstraZeneca noted in their release that the trial will continue through the final analysis of OS for the first arm with the combination of PD-L1 inhibition, CTLA-4 inhibition, and chemotherapy.
Durvalumab is being investigated in combination with tremelimumab in a number of clinical trials in solid tumors, including nonsmall cell lung cancer, bladder cancer, head and neck cancer, and liver cancer, as well as hematologic malignancies. Durvalumab plus tremelimumab in combination with chemotherapy has demonstrated acceptable tolerability and evidence of clinical activity in a previous phase Ib study (NCT02537418).
Imfinzi improves overall survival at interim analysis in the Phase III CASPIAN trial in 1st-line extensive-stage small cell lung cancer [press release]. Wilmington, DE: AstraZeneca; June 27, 2019. https://bit.ly/2RFpKlz. Accessed June 27, 2019.