"While the MSI-H biomarker is only present in a very small proportion of patients with gastroesophageal cancer, the greatly improved prognosis even in stage-4 disease when immunotherapy is utilized speaks to the importance of checking for this biomarker," Dr. Joseph Chao of City of Hope Comprehensive Cancer Center, in Duarte, California, told Reuters Health by email.
Earlier research has linked immunotherapy with improved outcomes in patients who have received previous treatment for MSI-H cancers. Dr. Chao and his colleagues sought to compare the antitumor activity of pembrolizumab therapy and chemotherapy regardless of the line of therapy in which the immunotherapy was used.
For their study, published in JAMA Oncology, they analyzed data from the phase-2 KEYNOTE-059 single-arm trial (third-line treatment or higher), the KEYNOTE-061 phase-3 trial comparing pembrolizumab monotherapy and chemotherapy (second-line treatment) and the KEYNOTE-062 phase-3 trial comparing pembrolizumab monotherapy, pembrolizumab plus chemotherapy and chemotherapy alone (first-line treatment). Median follow-up ranged from 5.6 to 11.3 months across the studies.
Eighty-four of the 1,614 trial participants had confirmed MSI-H. For these patients, median overall survival (OS) with pembrolizumab monotherapy was not reached in KEYNOTE-059 or KEYNOTE-061, while it was 8.1 months for chemotherapy alone in KEYNOTE-061.
In KEYNOTE-062, median OS was not reached for pembrolizumab monotherapy or pembrolizumab plus chemotherapy, but was 8.5 months for chemotherapy alone.
The drug also prolonged progression-free survival and provided durable beneficial responses compared to chemotherapy alone among patients who had received two or more previous lines of therapy, one previous line of therapy or no previous therapy.
"The findings of this analysis support MSI-H status as a biomarker for pembrolizumab therapy among patients with advanced gastric or gastroesophageal junction cancer and warrant its prospective validation in ongoing first-line studies," the researchers write.
Dr. Chao added, "With the anticipated increased use of immunotherapy with chemotherapy as the initial treatment for stage-4 gastroesophageal cancer, this study would support first-line application of immunotherapy greatly improving outcomes for these patients when their cancer harbors the MSI-H biomarker."
Dr. Efrat Dotan, co-author of an accompanying editorial, told Reuters Health by email that the study "highlights the importance of MSI testing among patients with metastatic gastric and gastroesophageal junction (G/GEJ) cancers and provides evidence supporting the use of immunotherapy for treatment of patients with MSI-High G/GEJ tumors."
"Through this post hoc analysis of three large clinical trials, the authors were able to demonstrate the significant benefit derived from immunotherapy among this rare group of patients in all lines of treatment," added Dr. Dotan of Fox Chase Cancer Center, in Philadelphia. "Based on this data and as recommended by National Comprehensive Cancer Network guidelines, MSI testing should be routinely preformed in any newly diagnosed metastatic G/GEJ patients."
Merck Sharp and Dohme, which sells pembrolizumab as Keytruda, funded the study and paid for medical writing. Dr. Chao has financial ties to the company.
SOURCE: https://bit.ly/3wFMy9e and https://bit.ly/2RleLlt JAMA Oncology, online April 1, 2021.
By David Douglas
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