Researchers have revealed that combining pembrolizumab with other treatments may reduce the size of target tumors, resulting in a higher response rate for patients with advanced non–small cell lung cancer (NSCLC), according to a recent study published by Gutierrez et al in Nature Medicine.
“We are excited to share these new findings, which show promising results for pembrolizumab-based treatment regimens for patients with advanced NSCLC,” highlighted senior study author Roy Herbst, MD, PhD, the Ensign Professor of Medicine (Medical Oncology), Professor of Pharmacology, and Assistant Dean for Translational Research at the Yale School of Medicine; Deputy Director at the Yale Cancer Center; and Chief of Medical Oncology and Director of the Center for Thoracic Cancers at the Smilow Cancer Hospital. “We are very pleased with how the treatment regimens helped improve survival outcomes for patients,” he added.
Study Methods and Results
In the ongoing phase II KEYNOTE-495/KeyImPaCT study, the researchers categorized the participants into four biomarker-defined groups based on similarities in their tumor microenvironments—including their gene expression and the amount of gene mutations in the cancer cells. The patients in each group were then randomly assigned to receive pembrolizumab in combination with one of three other cancer therapeutics: lenvatinib, quavonlimab, or favezelimab.
“The study's approach of categorizing patients into biomarker-defined subgroups allows us to identify potential unique resistance mechanisms and tailor treatment strategies accordingly,” Dr. Herbst explained.
The researchers discovered that the objective response rates ranged from 0% to 12% in group 1, 27.3% to 33.3% in group 2, 13.6% to 40.9% in group 3, and 50% to 60% in group 4—with the ranges encompassing the results of the different treatment combinations. They also reported at least a 30% reduction in the target tumor size in more than 58% of the patients in group 4. Further, progression-free survival was highest for group 4, ranging from 6.3 months to 17.8 months. The most common treatment-related adverse events included hypertension, itchy skin, and fatigue.
Conclusions
The interim results from the study demonstrated that each of the treatment combinations provided antitumor activity, particularly in group 4. The researchers emphasized that additional research will provide more insight on optimal combinations targeting specific molecular subtypes in NSCLC and other tumor types.
“These findings reinforce the importance of personalized medicine in improving outcomes for patients with NSCLC and pave the way for further advancements in pembrolizumab combination therapies,” concluded Dr. Herbst.
Disclosure: The research in this study was funded by Merck Sharp & Dohme. For full disclosures of the study authors, visit nature.com.
