A Second Immunotherapy Approval After Surgery for Non-Small Cell Lung Cancer

For stage IB (T2a, meaning a tumor diameter ≥4 cm), stage II or IIIA non-small cell lung cancer (NSCLC) following surgery and platinum-based chemotherapy, adjuvant pembrolizumab (Keytruda, Merck) immunotherapy received FDA (United States Food and Drug Administration) approval on 26 January 2023.

This is the 2nd approval for adjuvant immunotherapy after surgery for early-stage non-small cell lung cancer. Atezolizumab (Tecentriq) had previously received FDA approval for these patients in October 2021 (see the related approval).

FDA Approval Based on KEYNOTE-091

Pembrolizumab's efficacy was evaluated in KEYNOTE-091, a multicenter, randomized, triple-blind, placebo-controlled study. Patients had not received neoadjuvant (preoperative tumor-shrinking) radiotherapy or chemotherapy. Patients were randomized to receive, for up to 1 year and every 3 weeks, either 200 mg of intravenous pembrolizumab or placebo in a 1:1 ratio. Stratification factors included receipt of adjuvant chemotherapy and the country of enrollment. Of the 1177 randomized patients, 1010 (86%) received adjuvant platinum-based chemotherapy after complete surgical removal of the tumor.

The main efficacy outcome targeted in the study was investigator-assessed disease-free survival.

In cancer, disease-free survival (disease-free survival, DFS) is the time after cancer treatment during which the cancer does not reappear. This period may not indicate whether the cancer will return, but it shows that the patient has responded to treatment; the longer it is, the better the response. 

Results

The trial met its primary endpoint, demonstrating a statistically significant improvement in disease-free survival.

Among patients who received adjuvant chemotherapy, median disease-free survival was 58.7 months (95% CI: 39.2, not reached) in the pembrolizumab arm and 34.9 months in the placebo arm (95% CI: 28.6, not reached) (hazard ratio=0.73; 95). %CI: 0.60, 0.89]).

In an exploratory subgroup analysis of the 167 patients who did not receive adjuvant chemotherapy, the hazard ratio for disease-free survival was 1.25 (95% CI: 0.76, 2.05); this patient group therefore did not benefit from immunotherapy.

Adverse events observed in KEYNOTE-091 were generally similar to those in other NSCLC patients receiving Keytruda alone, except for hypothyroidism (22%), hyperthyroidism (11%) and pneumonitis (7%). Two patients developed myocarditis (inflammation of the heart muscle) that led to death.

Pembrolizumab is recommended until disease recurrence, unacceptable side effects or for up to 12 months, with dosing every 3 weeks at 200 mg or every 6 weeks at 400 mg.