Keytruda Approved as Neoadjuvant/Adjuvant Treatment for Resectable NSCLC

The Food and Drug Administration (FDA) has approved Keytruda^® (pembrolizumab) for the treatment of patients with resectable (tumors ≥4cm or node positive) non-small cell lung cancer (NSCLC) in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

The approval was based on data from the randomized, double-blind, phase 3 KEYNOTE-671 trial (ClinicalTrials.gov Identifier: NCT03425643), which included 797 patients with previously untreated and resectable stage II, IIIA, or IIIB (N2) NSCLC. Study participants were randomly assigned 1:1 to receive either pembrolizumab or placebo, with platinum doublet chemotherapy every 3 weeks for 4 cycles (neoadjuvant treatment) followed by either continued single-agent pembrolizumab or placebo, every 3 weeks for up to 13 weeks (adjuvant treatment). 

The coprimary endpoints were overall survival (OS) and event free survival (EFS), defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. 

Findings showed statistically significant improvements in OS and EFS for patients treated with pembrolizumab compared with those who received placebo. Median OS was not reached in the pembrolizumab arm (95% CI, not reached [NR], NR) and was 52.4 months (95% CI, 45.7, NR) in the placebo arm (hazard ratio [HR], 0.72 [95% CI, 0.56-0.93]; P =.0103). Median EFS was not reached in the pembrolizumab arm (95% CI, 34.1 months, NR) and was 17 months (95% CI, 14.3-22.0) in the placebo arm (HR, 0.58 [95% CI, 0.46-0.72]; P <.0001). 

Additionally, a statistically significant difference was observed with pembrolizumab vs placebo in pathological complete response (pCR) rate (18.1% vs. 4.0%, respectively; P <.0001) and major pathological response (mPR) rate (30.2% vs. 11.0%, respectively; P <.0001). 

The safety profile of pembrolizumab in combination with platinum containing chemotherapy, given as neoadjuvant treatment and continued as single agent adjuvant treatment, was generally similar to that observed in other clinical trials across tumor types. The most common adverse reactions reported in at least 20% of patients were nausea, fatigue, neutropenia, anemia, constipation, decreased appetite, decreased white blood cell count, musculoskeletal pain, rash, cough, vomiting, diarrhea and dyspnea. 

“There remains a need for treatment options to improve outcomes for patients with earlier stages of non-small cell lung cancer,” said Dr Heather Wakelee, principal investigator for KEYNOTE-671, thoracic medical oncologist and professor of medicine at Stanford University and past president of the International Association for the Study of Lung Cancer. “This important milestone has the potential to change the current treatment paradigm for resectable non-small cell lung cancer that is greater than 4 centimeters or has lymph node involvement, by offering an immunotherapy-based regimen that has demonstrated statistically significant improvements in overall survival and event free survival compared to a placebo and chemotherapy regimen.”

References

1. FDA approves Keytruda® (pembrolizumab) for treatment of patients with resectable (T≥4 cm or N+) NSCLC in combination with chemotherapy as neoadjuvant treatment, then continued as a single agent as adjuvant treatment after surgery. News release. Merck. October 16, 2023. Accessed October 17, 2023. https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-for-treatment-of-patients-with-resectable-t%e2%89%a54-cm-or-n-nsclc-in-combination-with-chemotherapy-as-neoadjuvant-treatment-then-continued-as-a-single/
2. Keytruda. Package insert. Merck; 2023. Accessed October 17, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125514s139lbl.pdf

This article originally appeared on MPR