Breakthrough lung cancer therapies shrink tumors and improve survival outcomes for patients
[July13, 2023: Staff Writer, The Brighter Side of News]
The science of cancer treatment is continually reshaping as we discover more about the nuanced characteristics of the disease. (CREDIT: Creative Commons)
The science of cancer treatment is continually reshaping as we discover more about the nuanced characteristics of the disease. A recently published study in Nature Medicine underscores the potential for combining pembrolizumab with other treatments to enhance the response rate in patients with advanced stage III non-small cell lung cancer (NSCLC). The Yale Cancer Center-led study offers renewed hope for these patients, demonstrating that this novel treatment approach could shrink the size of target tumors more effectively.
"We are excited to share these new findings, which show promising results for pembrolizumab-based treatment regimens for patients with advanced NSCLC,” enthused senior author Roy Herbst, deputy director of Yale Cancer Center and assistant dean for translational research at Yale School of Medicine. “We are very pleased with how the treatment regimens helped improve survival outcomes for patients.”
Although pembrolizumab, also known under the brand name Keytruda, is an approved therapy for patients with NSCLC, it has only proven effective for a subset of them. Treatment failures, researchers found, are frequently due to differences in the tumor microenvironment.
To address this hurdle, the team developed a unique approach within their phase II study (KEYNOTE-495/KeyImPaCT), categorizing patients into four biomarker-defined groups based on gene expression and the extent of gene mutation in the cancer cells. The purpose was to align treatments with the specific characteristics of the tumor microenvironment in each patient.
This categorization allowed for a more tailored approach to treatment. “The study's approach of categorizing patients into biomarker-defined subgroups allows us to identify potential unique resistance mechanisms and tailor treatment strategies accordingly,” said Herbst.
Patients within each of the four groups were randomly allocated to receive pembrolizumab combined with one of three other cancer treatments: lenvatinib (Lenvima), quavonlimab, or favezelimab. This targeted approach resulted in a significant reduction in tumor size, especially in patients who were part of group IV, proving the potential efficacy of combination treatments.
The study examined the objective response rate (ORR), progression-free survival (PFS), and safety. The ORR measures the proportion of patients who had a partial or complete response to the treatment. The reported ORR ranges were quite varied across groups - 0% to 12% in group I, 27.3% to 33.3% in group II, 13.6% to 40.9% in group III, and an impressive 50% to 60% in group IV. This highlights the pronounced impact of the tailored treatment regimen, particularly for group IV, where over 58% of patients saw at least a 30% reduction in the size of the target tumor.
Study design and patient disposition. (CREDIT: Nature Medicine)
The duration of progression-free survival - the length of time during and after the treatment a patient lives with the disease without it getting worse - also reflected significant improvements, particularly for group IV.
The range was from 6.3 months to 17.8 months, an encouraging step forward for patients with advanced NSCLC. As for safety, the most common treatment-related adverse events noted in the study included hypertension, itchy skin, and fatigue.
“The 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,” Herbst pointed out.
Best percentage change from baseline in target lesion size in the pembrolizumab + lenvatinib and pembrolizumab + quavonlimab. (CREDIT: Nature Medicine)
The interim results from the study suggested that each of the treatment combinations provided anti-tumor activity, particularly in group IV. These results are just the tip of the iceberg, and additional research from the trial is set to offer further insights on optimal combinations targeting specific molecular subtypes in NSCLC and other tumor types.
The study was spearheaded by Dr. Martin Gutierrez at Hackensack University Medical Center and was generously funded by Merck Sharp & Dohme, LLC, a subsidiary of Merck. As the medical community continues to unravel the complexities of lung cancer, this study stands as a testament to the power of personalized treatment regimens and a beacon of hope for NSCLC patients worldwide.
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