Antibiotics may lower efficacy of immune checkpoint inhibitors for kidney cancer
A recent study presented at the ASCO Genitourinary Cancers Symposium 2017 held in Orlando, Florida, US showed that antibiotic use in patients with metastatic renal cell carcinoma (mRCC) may dampen the efficacy of PD-1/PD-L1 inhibitors.
A retrospective analysis of 80 mRCC patients treated in prospective trials at the Gustav Roussy Cancer Institute, Paris, France with PD-1/PD-L1 inhibitors revealed that patients who received antibiotics within 1 month prior to the start of immunotherapy deteriorated faster as compared with those who did not receive antibiotics recently (median progression-free survival, 2.3 months vs 8.1 months; p<0.001). [ASCO GU 2017, abstract 462]
The patients (20 percent) who were treated with antibiotics (mostly beta-lactam or fluoroquinolone antibiotics) also had a lower objective response rate compared with those who did not receive any antibiotics within 1 month prior to their first dose of immunotherapy (p<0.002).
The statistical significance persisted even after the researchers controlled for age, gender, International Renal-Cell Carcinoma Database Consortium (IMDC) risk classification, tumour burden and proton pump inhibitor use in a multivariate analysis.
There was also a trend towards worse overall survival in those treated with antibiotics, although longer follow-up is necessary to make conclusions.
“These early findings show that doctors prescribing cancer immunotherapy should pay close attention to antibiotic use … This research may be relevant to more than just kidney cancers, as antibiotics are commonly prescribed to patients with cancer,” said investigator Dr Lisa Derosa from the Gustav Roussy Cancer Institute, Paris, France during a press conference prior to the symposium.
A majority of patients enrolled in the study were male (65 percent) with clear-cell type histology (88 percent), underwent nephrectomy (80 percent), and were treated with anti–PD1/PD-L1 monotherapy (83 percent). The rest were treated with either anti–PD-1 plus CTLA-4 immunotherapy (13 percent) or anti–PD-L1 immunotherapy plus bevacizumab (4 percent).
“The observations that Derosa made had some consistency with preclinical observation … We may be able to offer some insights as to whether or not bacterial composition of the gut could affect clinical outcomes, and that might help us guide antibiotic use,” commented Dr Sumanta Pal of the Department of Medical Oncology and Therapeutics Research and Kidney Cancer Program at City of Hope, Duarte, California, US, who moderated the press conference.
“One has to consider the fact that antibiotics are used under circumstances of necessity. I would not forgo treatment of any active infection and I would still use it as medically necessary,” Pal added.
Future directions of research include enrolling additional patients for the study, and continuing studies to pinpoint specific gut bacteria that affect response to immune checkpoint inhibitors and to determine the types of antibiotics that have the greatest impact on outcomes.
Previous preclinical studies using mouse models have already suggested an association between antibiotics and the efficacy of immune checkpoint inhibitors. [Science 2015;350:1079-1084]