Frontline Durvalumab Plus Tremelimumab and Chemo Improves OS for Stage IV NSCLC

Dave Fredrickson

The combination of durvalumab (Imfinzi) plus tremelimumab and platinum-based chemotherapy resulted in a significant improvement in overall survival (OS) compared with chemotherapy alone in the frontline treatment of patients with stage IV non–small cell lung cancer (NSCLC), according to results from the final analysis of the phase 3 POSEIDON trial (NCT03164616).¹

The immunotherapy regimen also continued to significantly improve progression-free survival in this patient population over chemotherapy alone, according to an announcement from AstraZeneca. No new safety signals were observed and the combination with tremelimumab was noted to be comparable to that of durvalumab and chemotherapy alone in that the addition of the CTLA-4 antibody did not result in increased treatment discontinuation.

The data will be shared at an upcoming medical conference.

“We are pleased to see the POSEIDON phase 3 trial demonstrate, for the first time, a significant and clinically meaningful OS for [durvalumab] plus tremelimumab with chemotherapy in metastatic NSCLC,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, stated in a press release. “We were particularly pleased by the safety profile. We’ve seen encouraging uptake of novel combinations in this setting and believe this new approach will add a further option for patients with high unmet medical need. We look forward to discussing next steps with regulatory authorities.”

In the open-label, multicenter, global, phase 3 POSEIDON trial, investigators evaluated durvalumab in combination with platinum-based chemotherapy or with tremelimumab and chemotherapy compared with chemotherapy alone as a frontline regimen for a total of 1013 patients with either nonsquamous or squamous, metastatic NSCLC.

To be eligible for enrollment, patients needed to be at least 18 years of age, histologically or cytologically documented stage IV disease, confirmed tumor PD-L1 status before randomization, tumors without activating EGFR mutations and ALK fusions, and an ECOG performance status of 0 or 1.² They could not have previously received chemotherapy or any other systemic therapies for metastatic disease, nor could they have been exposed to immune-mediated therapy, with the exception of anticancer vaccines.

Participants in the investigational arms were given a flat dose of 1500 mg of durvalumab with up to 4 cycles of chemotherapy once every 3 weeks or durvalumab in combination with 75 mg of tremelimumab with chemotherapy, followed by maintenance treatment with durvalumab or durvalumab and 1 dose of tremelimumab on a once-every-4-weeks dosing schedule. Those in the control arm were able to receive up to 6 cycles of chemotherapy.

Pemetrexed maintenance was permitted in all arms for patients with nonsquamous disease, if administered in the induction phase of treatment.

The co-primary end points for the trial included PFS and OS in the durvalumab plus chemotherapy arm, while secondary end points were PFS and OS in the durvalumab plus tremelimumab and chemotherapy arm.

Previously, in October 2019, data showed that the combination of durvalumab plus tremelimumab and chemotherapy resulted in a statistically significant improvement in PFS, meeting one of the primary end points of the trial.³ As the PFS end point was also met for durvalumab plus chemotherapy, the prespecified statistical analysis plan permitted independent OS testing for the triplet arm.

References

1. Imfinzi and tremelimumab with chemotherapy demonstrated overall survival benefit in POSEIDON trial for 1st-line stage IV non-small cell lung cancer. News release. AstraZeneca. May 7, 2021. Accessed May 7, 2021.
2. Study of durvalumab + tremelimumab with chemotherapy or durvalumab with chemotherapy or chemotherapy alone for patients with lung cancer (POSEIDON). ClinicalTrials.gov. Updated April 28, 2021. Accessed May 7, 2021. https://clinicaltrials.gov/ct2/show/NCT03164616
3. IMFINZI (durvalumab) and IMFINZI plus tremelimumab delayed disease progression in phase III POSEIDON trial for 1st-line treatment of stage IV non-small cell lung cancer. News release. AstraZeneca. October 28, 2019. Accessed May 7, 2021. https://bwnews.pr/3uvpatl