The combination of durvalumab, tremelimumab, and chemotherapy showed statistically significant and clinically meaningful overall survival benefit compared to chemotherapy alone for the first-line treatment of patients with metastatic non-small cell lung cancer.
The combination of durvalumab (Imfinizi), tremelimumab, and chemotherapy showed statistically significant and clinically meaningful overall survival (OS) benefit compared to chemotherapy alone for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC), according to a press release by AstraZeneca.1
Durvalumab is the current standard of care for unresectable, stage III NSCLC after chemoradiation. Currently, it is the only immunotherapy approved for the curative-intent setting of this malignancy. The agent is also indicated for the treatment of extensive-stage small cell lung cancer.
“We are pleased to see the POSEIDON phase 3 trial demonstrate, for the first time, a significant and clinically meaningful overall survival benefit for Imfinzi plus tremelimumab with chemotherapy in metastatic non-small cell lung cancer. We were particularly pleased by the safety profile,” said Dave Fredrickson the executive vice president of the oncology business unit at AstraZeneca in a press release.
The phase 3 POSEIDON trial (NCT03164616) aimed to compare the efficacy of durvalumab plus tremelimumab with chemotherapy versus durvalumab with chemotherapy or chemotherapy alone in patients with metastatic NSCLC that lack an activating EGFR mutation and ALK fusions.
The randomized, parallel assignment study has an estimated enrollment of 1193 participants. Primary outcomes of the study included OS up to 3 years after randomization and progression-free survival (PFS) up to 4 years after randomization. Secondary outcomes included objective response rate (ORR), duration of response (DOR), time from randomization to second progression, the proportion of patients alive and progression-free 12 months from randomization, best OR, pharmacokinetics, immunogenicity, health-related quality of life, disease-free symptoms, and changes in World Health Organization (WHO) and ECOG performance status. The other outcomes measured were the safety and tolerability of the therapies.
The study was split into 3 arms. In arm 1, patients received a triplet combination of durvalumab, tremelimumab, and chemotherapy. In arm 2, patients received durvalumab monotherapy and chemotherapy, and in arm 3, patients received chemotherapy alone.
In order to participate, patients must be 18 years old or older, have histologically or cytologically documented stage IV NSCLC, confirmed tumor PD-L1 status prior to randomization, and tumors must lack activating EFGR mutations and ALK fusions. Patients were not permitted to havv received prior chemotherapy or any other systemic therapy for metastatic NSCLC. Other requirements for enrollment included having a WHO/ECOG performance status of 0 or 1, and no prior exposure to immune-mediated therapy. Patients with mixed small-cell lung cancer and NSCLC histology, active or prior documented autoimmune or inflammatory disorders, brain metastases or spinal cord compression unless the patient’s condition is stable and off steroids, and active infections including hepatitis B, HIV, or tuberculosis are not eligible to participate.
An earlier report from the POSEIDON study showed that the trial reached the coprimary end point of PFS. The study is ongoing and actively recruiting patients with NSCLC whose tumor lack activating EGFR mutation and ALKfusions.2 So far in the study, no new safety signals were reported. The addition of durvalumab to the combination did not lead to an increase in treatment discontinuation.1
“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,” Fredrickson stated.
The data from POSEIDON will be presented at an upcoming medial meeting.