Can Antibiotic Therapy for Cancer Improve Treatment Response to Immune Checkpoint Inhibitors?

Prior antibiotic therapy may be associated with worse treatment response to immune checkpoint inhibitors and overall survival in patients with cancer, according to the results of a small study published in JAMA Oncology.

In the study of 196 patients with non–small-cell lung cancer (NSCLC), melanoma, and other tumor types who received immune checkpoint inhibitors, prior antibiotic use was associated with a median overall survival of 2 months for patients with prior antibiotic therapy compared with 26 months for patients with no prior antibiotic therapy (hazard ratio [HR]=7.4; P<.001).

“We didn’t really find a lot of difference in whether or not the patients received antibiotics during the course of immunotherapy,” study author David J. Pinato, MD, PhD, Imperial College London, United Kingdom, said in an interview with JAMA Oncology.  “This suggests that it’s the timing of antibiotics that is crucial to shaping this relationship.”

Concurrent antibiotic therapy was not associated with worse overall survival (HR=.9; P=.76). Despite this, the researchers suggested that “clinicians should carefully the weigh the pros and cons of prescribing broad-spectrum antibiotics prior to immune checkpoint inhibition treatment.”

For the study, prior antibiotic use was defined as antibiotic treatment administered within 30 days from commencement of immune checkpoint inhibitor therapy.

The patients were recruited from two tertiary academic referral centers in London between January 2015 and April 2018. Among the patients, 119 had NSCLC, 38 had melanoma, and 39 had other tumor types. The majority of patients (81%) had a performance status of 0 to 1.

Overall, 29 patients had received prior antibiotics, most commonly as treatment for respiratory tract infections (55%).

In addition to the difference in survival, patients with prior antibiotic treatment were also more likely to discontinue immune checkpoint inhibitors due to disease progression (P<.001) and to die of progressive disease while on therapy (P=.03).

Worse overall survival among patients with prior antibiotic use was consistent among patients with NSCLC, melanoma, and other tumor types (P<.001 for all).

In a multivariable analysis, Pinato and colleagues confirmed that prior antibiotic use was associated with overall survival independent of tumor site, disease burden, and performance status.

“Our study suggests that the timing of antibiotic exposure is crucial in dictating its interaction with response to immunotherapy, leading us to postulate a potential ‘priming’ effect of prior antibiotics on patients’ anticancer immunity,” the researchers wrote. “Moreover, we found prior antibiotics to be not only associated with worse overall survival but also strongly associated with radiologic responses to immune checkpoint inhibitors, an association that is independent from any potential association with comorbidities and corroborates the important link between antibiotic use and response to immune checkpoint inhibition therapy.”