First-line treatment with Imfinzi (durvalumab) combined with standard chemotherapy significantly prolongs the life of people with extensive-stage small cell lung cancer (SCLC), final results of the CASPIAN Phase 3 trial show.
Approval of the combination for this type of aggressive lung cancer is under review by regulatory authorities in the U.S., E.U., and Japan. In the U.S., a final decision is expected by the end of March, with the combo therapy being evaluated under priority review.
Imfinzi is an immune checkpoint inhibitor developed by AstraZeneca and approved by the U.S. Food and Drug Administration to treat advanced cancer of the bladder and urinary tract, and also of non-small cell lung cancer. The therapy is given via intravenous infusion, or directly into the bloodstream.
Imfinzi’s benefits for treating extensive-stage SCLC — meaning the cancer has spread in the lungs or to other parts in the body — were evaluated in the global CASPIAN trial (NCT03043872), which tested Imfinzi combined with chemotherapy and tremelimumab, an experimental immunotherapy. Tremelimumab is an antibody that blocks the CTLA-4 protein, ultimately intended to prime the immune response to cancer and induce cancer cell death.
The trial included 805 untreated patients with extensive-stage SCLC, who were randomly assigned to receive either chemotherapy alone (etoposide plus cisplatin or carboplatin) — which served as the control group — a combination of Imfinzi plus chemotherapy, or a triple combo of Imfinzi, tremelimumab, and chemotherapy.
Imfinzi-treated patients completed four cycles of chemotherapy, while those from the control group received up to six such cycles plus optional prophylactic cranial irradiation, a type of radiation therapy that destroys cancer cells.
A preliminary analysis reported in June 2019 showed that CASPIAN met one of its primary efficacy measures or endpoints: Imfinzi plus standard-of-care chemotherapy improved patients’ overall survival in a significant and clinically meaningful way, compared to chemotherapy alone.
Results released soon after showed that Imfinzi increased patients’ median overall survival from 10.3 to 13.0 months, corresponding to a 27% reduction in the risk of death.
At 18 months of follow-up, 33.9% of patients receiving Imfinzi and chemotherapy were alive, compared with 24.7% of those in the control group.
The safety and tolerability profile of Imfinzi in combination with chemotherapy was consistent with previous studies.
The incidence of severe (grade 3) and life-threatening (grade 4) adverse events was similar in the two groups (61.5% in the Imfinzi group and 62.4% in the control group). Treatment drop-outs were also similar at 9.4% in both groups.
Now, Astra Zeneca has announced that the final analysis of the CASPIAN study validated the sustained and meaningful improvements in survival in patients treated with Imfinzi-chemotherapy. It also shows that adding tremelimumab brings no further benefits.
Safety remains consistent with the known profiles of each treatment. The data will be presented at a forthcoming medical meeting.
“We are pleased to see the sustained and meaningful survival benefit of Imfinzi for patients with small cell lung cancer after more than two years median follow up,” José Baselga, MD, PhD, Astra Zeneca’s executive vice president of oncology research and development, said in a press release. “We have already received the first global regulatory approval for Imfinzi with etoposide plus either carboplatin or cisplatin and remain on track for more approvals soon as we provide patients an important new 1st-line treatment option.”
Imfinzi given after concurrent chemoradiation therapy is being evaluated in the Phase 3 ADRIATIC trial (NCT03703297) in patients with limited-stage SCLC, with results expected in 2021. The trial is recruiting patients in several countries worldwide. More information on contacts available here.