Durvalumab Misses OS End Point in PEARL Trial in Advanced, PD-L1–High NSCLC

Durvalumab monotherapy failed to elicit a statistically significant improvement in overall survival vs platinum-based chemotherapy as frontline treatment in patients with stage IV non–small cell lung cancer with at least 25% positivity of PD-L1 on tumor cells, or in a subgroup of patients at low risk of early mortality.

Durvalumab (Imfinzi) monotherapy failed to elicit a statistically significant improvement in overall survival (OS) vs platinum-based chemotherapy as frontline treatment in patients with stage IV non–small cell lung cancer (NSCLC) with at least 25% positivity of PD-L1 on tumor cells, or in a subgroup of patients at low risk of early mortality, according to topline findings from the phase 3 PEARL trial (NCT03003962).1

However, there was a clinically meaningful improvement in OS with durvalumab in the subset of patients with PD-L1 tumor expression greater than 50%, which comprised a secondary end point of the trial.

The safety and tolerability profile for durvalumab was largely consistent with the established profile of the agent, and no new safety signals were identified. The data will be shared sometime in the future.

“With PEARL, we set out to answer important scientific questions in the treatment of metastatic non-small cell lung cancer at a time when patient selection for immune checkpoint inhibitors was still evolving. We are encouraged to see patients in the metastatic setting at a higher level of PD-L1 tumor expression demonstrate the most benefit with Imfinzi monotherapy treatment, as is commonly seen in this class. We remain steadfast in our dedication to developing new and improved medicines and regimens for patients with lung cancer across our diverse portfolio,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said in a press release.

PEARL was a randomized, open-label, multicenter, global phase 3 trial that sought to evaluate single-agent durvalumab vs investigator’s choice of platinum-based chemotherapy as frontline therapy in patients with metastatic NSCLC.2 Investigator’s choice of therapy could be 1 of 5 standard chemotherapy regimens: paclitaxel and carboplatin, gemcitabine and cisplatin, gemcitabine and carboplatin, pemetrexed (Alimta) and cisplatin, or pemetrexed and carboplatin.

Eligible patients had tumors expressing high levels of PD-L1, defined as at least 25% positivity of tumor cells (TC). The largely Asian trial population included smokers and non-smokers and those with squamous and nonsquamous histology.

PEARL excluded patients with certain EGFR mutations or ALK fusions, those with prior exposure to chemotherapy or other systemic therapy for advanced NSCLC, active brain metastases, mixed small cell lung cancer and NSCLC histology or sarcomatoid variant, or active or prior history of autoimmune or inflammatory disorders.

The coprimary end points were OS in patients whose tumors expressed high levels of PD-L1 and OS in a subgroup of patients identified as being at low risk of early mortality. Key secondary end points included the objective response rate, duration of response, progression-free survival (PFS), second PFS, and health-related quality of life.

References

  1. Update on PEARL phase III trial of Imfinzi monotherapy in stage IV non-small cell lung cancer. News release. AstraZeneca. December 19, 2022. Accessed December 19, 2022. https://bit.ly/3WsH1Pd
  2. Study of durvalumab alone or chemotherapy for patients with advanced non–small-cell lung cancer (PEARL). ClinicalTrials.gov. Updated December 13, 2022. Accessed December 19, 2022. https://clinicaltrials.gov/ct2/show/NCT03003962