Merck & Co.’s Keytruda has achieved a groundbreaking milestone in the treatment landscape for early-stage non-small cell lung cancer (NSCLC), a field previously described as “messy” by doctors. In a pivotal phase 3 trial, Keytruda demonstrated a remarkable overall survival advantage when administered both before and after surgery in patients with stage 2 to 3b NSCLC, as revealed by Merck on Tuesday. Notably, this trial signifies the first instance where an immunotherapy has delivered a statistically significant overall survival benefit for specific early-stage NSCLC patients. Dr. Marjorie Green, head of late-stage oncology development at Merck Research Laboratories, commented on this promising outcome.
This positive development coincides with an imminent FDA decision, expected by Monday, regarding the use of Keytruda as a continuous neoadjuvant-plus-adjuvant therapy in early-stage NSCLC. The trial has previously demonstrated success in achieving its primary endpoint by reducing the risk of tumor recurrence, progression, or death measured by the event-free survival (EFS) marker.
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Further insights into the updated Keynote-671 data will be unveiled at the European Society for Medical Oncology 2023 congress later this month. During this conference, researchers will also share results from the CheckMate-77T trial, evaluating Bristol Myers Squibb’s Opdivo in a similar perioperative setting for stage 2 to 3b NSCLC. BMS recently reported that the trial met its EFS goal. Collectively, these datasets are poised to provide much-needed clarity for physicians who have been grappling with the challenge of selecting the most suitable treatment for early-stage NSCLC in the context of surgery. Notably, Keytruda, Opdivo, Roche’s Tecentriq, and AstraZeneca’s Imfinzi have all demonstrated positive outcomes in this setting.
A pivotal question that has perplexed healthcare professionals is whether a PD-1/L1 inhibitor is necessary both before and after surgery. In a significant development, Opdivo secured FDA approval last March as a neoadjuvant therapy for use exclusively before surgery. This approval stemmed from data derived from the CheckMate-816 trial, revealing that the addition of Opdivo to chemotherapy improved event-free survival by 37% in stage 1b to 3a NSCLC.
“This is a significant milestone in the treatment of resectable non-small cell lung cancer, as it represents the first Phase 3 study to show a statistically significant overall survival benefit for these patients with stage II, IIIA or IIIB (T3-4N2) non-small cell lung cancer. These results build upon the previously reported event-free survival data, and demonstrate the potential for this KEYTRUDA-based regimen to help extend the lives of these patient. We’re excited by the progress we have made to help patients with earlier stages of non-small cell lung cancer, who are in need of additional treatment options.”
– Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories
An updated analysis released in March indicated a 38% reduction in the risk of death with the Opdivo regimen, although statistical significance had not yet been reached. Notably, Merck’s Keynote-671 study, unveiled at the American Society of Clinical Oncology annual meeting in June, showcased a 42% improvement in EFS, hinting at the likelihood of achieving its overall survival objective, as survival rates had already begun to diverge between Keytruda and the control arm after two years.
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Meanwhile, AstraZeneca had previously reported that perioperative Imfinzi reduced the EFS risk by 32% in stage 2 to 3b NSCLC, based on an interim analysis of the AEGEAN trial. The analysis of overall survival in that study remained ongoing.
Both Keytruda and Roche’s Tecentriq are currently approved for use as adjuvant therapy, specifically following surgery. The attainment of an overall survival benefit remains a pivotal factor in determining the optimal utilization of immunotherapy in the context of surgical interventions, as emphasized by Dr. Mark Awad of the Dana-Farber Cancer Institute during a discussion at ASCO in June.
This groundbreaking progress in early-stage NSCLC treatment underscores the potential for immunotherapy to transform the landscape, offering renewed hope to patients and clinicians alike. The forthcoming data presentations and regulatory decisions are eagerly awaited, promising to provide critical guidance for physicians in their quest to enhance patient outcomes in this challenging domain.
