FDA approves durvalumab for early-stage small cell lung cancer

On December 4, 2024, the Food and Drug Administration (FDA) granted approval for the use of durvalumab, commercially known as Imfinzi, produced by AstraZeneca. This approval is intended for adults with limited-stage small cell lung cancer (LS-SCLC) whose cancer has not shown progression after completing concurrent platinum-based chemotherapy and radiation treatment. Comprehensive prescribing details for Imfinzi will be made available on the Drugs@FDA platform.

The efficacy and safety of durvalumab were put to the test in the ADRIATIC trial (NCT03703297), a randomized, double-blind, placebo-controlled study that included 730 patients diagnosed with LS-SCLC. These patients had not experienced disease progression following their treatment with platinum-based chemotherapy combined with radiation therapy. Participants of the study were divided into three groups in equal measure: one group received durvalumab alone, the second group was treated with a combination of durvalumab and tremelimumab, and the third group was given a placebo.

The primary efficacy outcomes assessed in the study were overall survival (OS) and progression-free survival (PFS), which were evaluated by a blinded independent central review. The comparison was primarily made between patients receiving durvalumab as a single agent and those who were administered the placebo. The results demonstrated a significant improvement in overall survival for patients treated with durvalumab compared to those who received the placebo. Specifically, durvalumab showed a hazard ratio (HR) of 0.73 (95% CI: 0.57, 0.93; p-value 0.0104), with median overall survival recorded at 55.9 months (95% CI: 37.3, not reached) for the durvalumab group and 33.4 months (95% CI: 25.5, 39.9) for the placebo group.

Additionally, progression-free survival was also significantly enhanced in the durvalumab group compared to the placebo group, with a hazard ratio (HR) of 0.76 (95% CI: 0.61, 0.95; p-value 0.0161). The median progression-free survival was 16.6 months (95% CI: 10.2, 28.2) for the durvalumab arm, while it was 9.2 months (95% CI: 7.4, 12.9) for the placebo arm.

The common adverse reactions observed in the study, affecting at least 20% of the participants, included pneumonitis or radiation pneumonitis and fatigue. The recommended dosage of durvalumab for patients weighing 30 kg or more is 1,500 mg every four weeks, whereas for those weighing less than 30 kg, it is 20 mg/kg every four weeks, continuing until either disease progression or the onset of unacceptable toxicity, or for a maximum duration of 24 months.

This review process was part of Project Orbis, an initiative by the FDA Oncology Center of Excellence aimed at facilitating the concurrent submission and review of oncology drugs among international partners. For this specific review, the FDA collaborated with several international regulatory agencies including the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Switzerland’s Swissmedic (SMC). The European Medicines Agency (EMA) served as an official observer throughout this review process. The application reviews are potentially still ongoing within these other regulatory bodies.

In addition, this review utilized the Assessment Aid, a voluntary submission from the applicant designed to streamline the FDA's assessment process. The application received priority review and breakthrough designation, both part of FDA's expedited programs for serious conditions.