Antibiotics With Keytruda May Affect Survival in Non-Small Cell Lung Cancer

Antibiotics cause a significant negative impact on patients with non-small cell lung cancer who are being treated with Keytruda (pembrolizumab) alone, although there is not a similar impact on those treated with chemotherapy alone, according to data published in the Journal for ImmunoTherapy of Cancer.

Previously, studies have shown that taking other prescription medications, over-the-counter drugs or dietary supplements such as antibiotics can worsen survival in patients with non-small cell lung cancer following immune checkpoint inhibitors.

With this study, researchers sought to identify the effect the taking those medications prior to treatment with Keytruda or chemotherapy in patients with metastatic non-small cell lung cancer. Several factors of interest included objective response rate (the proportion of patients with tumor size reduction in a minimum time period), overall survival (length of time from start of treatment or diagnosis until the patient is still alive with the disease) and progression-free survival (length of time from during or after treatment that the patient is still alive with the disease but it does not worsen). A total of 950 patients received Keytruda and 595 patients received chemotherapy.

At the beginning of the study, in the Keytruda group, corticosteroid (drugs that lower inflammation), proton pump inhibitors (used to prevent and treat ulcers in the first part of the small intestine and the stomach) and antibiotics were associated a reduced response to radiology. Those drugs also had a significant association to a higher risk of disease progression and death.

For patients in the chemotherapy group, at the start of the study, corticosteroids and proton pump inhibitors led to a higher risk of death. In addition, corticosteroids contributed to a significantly higher risk of disease progression. There was no significant association with progression-free survival or overall survival with antibiotics in this group of patients.

Researchers also performed an analysis where they took certain factors into consideration. With this, antibiotics became a strong predictor, as the authors wrote, for worse overall survival and progression-free survival for those on Keytruda, although this was not observed in those on chemotherapy.

Corticosteroids were associated with a shorter overall survival and progression-free survival after treatment with both Keytruda alone and chemotherapy alone, meaning those patients taking them had a higher risk of death and disease progression.

Shorter overall survival was seen in patients in both the Keytruda and chemotherapy group with proton pump inhibitors.

Overall, another analysis showed that there were statistically significant interactions in both the Keytruda and chemotherapy groups with corticosteroids and proton pump inhibitors with overall survival and progression-free survival. Corticosteroids also had interactions with the objective response rate.

“The most striking and practice-informing finding is that antibiotic therapy exerts a detrimental effect on (objective response rate), (progression-free survival) and (overall survival) exclusively in patients treated with (Keytruda) monotherapy but not with chemotherapy,” the study authors wrote. “This is an important step forward in understanding the mechanistic basis of such interpretation that (antibiotics) might act as true immune-modulators rather than by masking an unrecognized association with underlying adverse prognostic features.”

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