Triple Combo Therapy Shows Potential as First-line Treatment in Stage 4 NSCLC

The addition of durvalumab (Imfinzi, AstraZeneca) and tremelimumab to chemotherapy improved progression-free survival (PFS) in patients with previously-untreated stage 4 non-small cell lung cancer (NSCLC), according to results from a phase 3 study.

NSCLC is the most common form of lung cancer, representing approximately 80% to 85% of patients diagnosed. For those with metastatic disease, only 1 in 10 survive 5 years after diagnosis, according to AstraZeneca.

Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1 and CD80. Based on the phase 3 PACIFIC trial, durvalumab is currently approved for unresectable, stage 3 NSCLC, as well as for previously-treated patients with bladder cancer. Tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, is being tested in combination with durvalumab across a range of cancers.

The phase 3 POSEIDON trial is evaluating durvalumab plus platinum-based chemotherapy or durvalumab, tremelimumab, and chemotherapy versus chemotherapy alone in the first-line treatment of patients with metastatic NSCLC. The study population included patients with either non-squamous or squamous disease and the full range of PD-1 expression levels.

In the experimental arms, patients were treated with a flat dose of 1500 mg of durvalumab with 4 cycles of chemotherapy once every 3 weeks or durvalumab plus 75 mg of tremelimumab, followed by maintenance therapy with durvalumab or durvalumab and 1 dose of tremelimumab on a once-every-4-weeks dosing schedule. Patients in the control group received up to 6 cycles of chemotherapy.

Overall, the results showed that patients treated with the combination of durvalumab plus chemotherapy versus chemotherapy alone had a statistically significant and clinically meaningful improvement in the final PFS analysis. Additionally, the triple combination of durvalumab plus tremelimumab and chemotherapy also demonstrated a statistically significant and clinically meaningful PFS improvement versus chemotherapy alone.

The triple combination delivered a similar safety profile compared with durvalumab plus chemotherapy and did not result in increased discontinuation of therapy, according to the study.

“The POSEIDON trial provides evidence of the efficacy of Imfinzi in patients with stage 4 non-small cell lung cancer,” Jose Baselga, executive vice president of Oncology R&D at AstraZeneca, said in a statement. “Clinical benefit was observed in a trial population that included a high proportion of patients with squamous disease and multiple choices of chemotherapy regimens. 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.”

Reference

Imfinzi and Imfinzi plus tremelimumab delayed disease progression in phase III POSEIDON trial for 1^st-line treatment of stage IV non-small cell lung cancer [news release]. AstraZeneca’s website. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2019/imfinzi-and-imfinzi-plus-tremelimumab-delayed-disease-progression-in-phase-iii-poseidon-trial-for-1st-line-treatment-of-stage-iv-non-small-cell-lung-cancer.html. Accessed October 29, 2019.