First-line durvalumab regimens extend PFS in metastatic NSCLC

The addition of durvalumab to chemotherapy extended PFS for patients with previously untreated stage IV non-small cell lung cancer, according to topline data from the randomized phase 3 POSEIDON trial.

The triple combination of durvalumab (Imfinzi, AstraZeneca) and tremelimumab (AstraZeneca) also prolonged PFS compared with chemotherapy alone, results showed.

The safety profile of durvalumab appeared consistent with prior studies. The addition of tremelimumab to durvalumab and chemotherapy did not dramatically alter the safety profile and did not lead to a higher rate of therapy discontinuation.

“Clinical benefit was observed in a trial population that included a high proportion of patients with squamous disease and multiple choices of chemotherapy regimens,” Jose Baselga, MD, PhD, executive vice president of oncology research and development at AstraZeneca, said in a company-issued press release. “Additionally, the potential to add tremelimumab to Imfinzi and chemotherapy may present an important treatment approach in this challenging setting, especially taking into consideration the favorable safety profile.”

Durvalumab is a human monoclonal antibody that binds to PD-L1. It is approved in 53 countries — including the United States — for treatment of patients with unresectable stage III NSCLC. It also is approved in the United States for previously treated patients with advanced bladder cancer.

Tremelimumab is an anti-CTLA-4 antibody under evaluation in clinical trials as treatment for NSCLC, bladder cancer, head and neck cancer, liver cancer and blood cancers.

The open-label, multicenter POSEIDON trial compared three regimens:

durvalumab dosed at 1,500 mg every 4 weeks with four cycles of platinum-based chemotherapy once every 3 weeks;

durvalumab plus tremelimumab dosed at 75 mg every 4 weeks and chemotherapy, followed by maintenance therapy with durvalumab alone or durvalumab plus one dose of tremelimumab; and

up to six cycles of chemotherapy alone.

Researchers enrolled patients with nonsquamous or squamous disease, and regardless of PD-L1 expression levels. However, they excluded patients with EGFR or anaplastic lymphoma kinase mutations.

Study protocol allowed for pemetrexed maintenance for patients with nonsquamous disease if it was given during the induction phase.

The trial met its primary endpoint, as results showed a statistically significant improvement in PFS among patients treated with durvalumab plus one of five standard-of-care platinum-based chemotherapy options compared with chemotherapy alone.

The trial also achieved a key secondary endpoint, as the combination of durvalumab, tremelimumab and chemotherapy also extended PFS compared with chemotherapy alone.

Assessment of OS — another primary endpoint — will continue, and data are expected in 2020.

HemOnc Today and Healio.com will continue to follow the trial and report on complete results when they are submitted for presentation at a future medical meeting.