Durvalumab/Tremelimumab Combo Plus Chemo Increases PFS in NSCLC

By Michael Vlessides, /alert Contributor
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When added to standard chemotherapy, combination therapy with durvalumab and the anti-CTLA4 antibody tremelimumab results in positive progression-free survival rates among patients with previously untreated stage IV non-small cell lung cancer (NSCLC), a new study has concluded.  

These findings open the door to a new potential treatment option for these patients, the researchers noted. 

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As part of the international, phase-III POSEIDON investigation (NCT03164616) -- a randomized, open-label, multi-center trial – the researchers compared three regimens in the first-line treatment of metastatic NSCLC: durvalumab plus platinum-based chemotherapy; durvalumab, tremelimumab and chemotherapy; and chemotherapy alone 

Participants comprised individuals with either non-squamous or squamous disease and the full range of PD-L1 expression levels. Patients were excluded from the trial if they had a mutation in the epidermal growth factor receptor (EGFR) gene or ALK gene. 

In the experimental arms, patients were treated with either: 1) a flat dose of 1,500 mg durvalumab with four cycles of chemotherapy once every three weeks; 2) durvalumab plus 75mg tremelimumab, followed by maintenance therapy with durvalumab; or 3) durvalumab and one dose of tremelimumab once every four weeks. By comparison, controls received as many as six cycles of chemotherapy. 

Maintenance therapy with pemetrexed was permitted in all arms in patients with non-squamous disease, if it had been administered during the induction phase. 

The study met one of its primary endpoints by demonstrating a statistically significant and clinically meaningful improvement in progression-free survival among individuals treated with the combination of durvalumab plus a broad choice of five standard-of-care platinum-based chemotherapy options, compared with chemotherapy alone. 

Similarly, triple-combination therapy with durvalumab plus tremelimumab and chemotherapy also demonstrated a statistically significant and clinically meaningful improvement in progression-free survival versus chemotherapy alone. 

The safety and tolerability of durvalumab was found to be consistent with its known safety profile. In the same vein, the safety profile of the triple combination was broadly similar to the durvalumab-chemotherapy combination, and did not result in increased discontinuation of therapy.

The findings drew praise from durvalumab’s manufacturer. “The POSEIDON trial provides evidence of the efficacy of durvalumab in patients with stage IV non-small cell lung cancer,” Jose Baselga, MD, PhD, 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 durvalumab and chemotherapy may present an important treatment approach in this challenging setting, especially taking into consideration the favorable safety profile,” Baselga added. 

Currently being conducted in 153 centers across 18 countries, the POSEIDON trial is continuing to assess overall survival; data from these analyses are expected to be released in 2020. 

Durvalumab is also being tested in stage IV NSCLC as monotherapy in the phase-III PEARL trial (NCT03003962).

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