The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:
On January 26, 2023, the Food and Drug Administration (FDA) approved pembrolizumab (Keytruda, Merck) for adjuvant treatment following resection and platinum-based chemotherapy for stage IB (T2a ≥4 cm), II, or IIIA non-small cell lung cancer (NSCLC).
View full prescribing information for Keytruda.
Efficacy was evaluated in KEYNOTE-091 (NCT02504372), a multicenter, randomized, triple-blind, placebo-controlled trial. Patients had not received neoadjuvant radiotherapy or chemotherapy. Patients were randomized (1:1) to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for up to 1 year. Stratification factors included receipt of adjuvant chemotherapy and region of the world. Of the 1177 patients randomized, 1010 (86%) received adjuvant platinum-based chemotherapy following complete resection.
The major efficacy outcome measure was investigator-assessed disease-free survival (DFS). The trial met its primary endpoint, demonstrating a statistically significant improvement in DFS in the overall population. In an exploratory subgroup analysis of the 167 patients who did not receive adjuvant chemotherapy, the DFS hazard ratio was 1.25 (95% CI: 0.76, 2.05). For patients who received adjuvant chemotherapy, median DFS was 58.7 months in the pembrolizumab arm (95% CI: 39.2, not reached) and 34.9 months in the placebo arm (95% CI: 28.6, not reached) (hazard ratio=0.73; 95% CI: 0.60, 0.89]).
The adverse reactions observed in KEYNOTE-091 were generally similar to those occurring in other patients with NSCLC receiving KEYTRUDA as a single agent, with the exception of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease recurrence, unacceptable toxicity, or up to 12 months.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
For information on the COVID-19 pandemic, see the following resources:
- FDA: Coronavirus Disease 2019 (COVID-19)
- NCI: Coronavirus: What People With Cancer Should Know
- CDC: Coronavirus (COVID-19)
Follow the Oncology Center of Excellence on Twitter @FDAOncology.
Please visit the FDA Hematology/Oncology (Cancer) Approvals & Safety Notifications webpage for a list of current and past approvals.