Nick Mulcahy

February 13, 2017

The efficacy of immunotherapy with checkpoint inhibitors may be reduced in patients who receive antibiotics in the month before starting their cancer treatment, according to a first-of-its-kind study from French researchers.

In a study of 80 patients with metastatic renal cell carcinoma (mRCC) treated with checkpoint inhibitors, disease progressed more quickly in those who received broad-spectrum antibiotics (n = 16) than in those who did not (median progression-free survival [PFS], 2.3 vs. 8.1 months; P < .001), said lead study author Lisa Derosa, MD, of the Gustave Roussy Cancer Institute, Paris-Sud University, Villejuif, France.

The significant negative effect on PFS held after adjustment for multiple prognostic risk factors, such as age, risk group, and tumor burden.

Dr Derosa discussed the retrospective study today at a presscast that precedes the Genitourinary Cancers Symposium (GUCS) 2017, in Orlando, Florida, which will be held later this week.

However, the data are hypothesis generating and not ready for clinical application, said Sumanta Pal, MD, a medical oncologist at the City of Hope Cancer Center in Los Angeles, California. Dr Pal is an expert from the American Society of Clinical Oncology who moderated the presscast.

"I certainly wouldn't forgo treating any infection," Dr Pal commented.

I certainly wouldn't forgo treating any infection Dr Sumanta Pal

Dr Derosa agreed, saying there was "no need to limit antibiotics" and that further prospective studies are needed.

Dr Pal acknowledged that the microbiome, or bacteria in various organs, has become a hot area of cancer research.

He explained that studies in mice have suggested that "immune-based therapies for cancer may have a very complex interplay with the host's microbiome." For example, this research has shown that the bacterial composition of the gut could affect the effectiveness of both PD-1 and CTLA-4 inhibitors.

Other results from patients receiving immunotherapy have shown that responses to therapy appear to be better in those patients who have a greater diversity of bacteria in their microbiome, as reported by Medscape Medical News.

This new study provides further evidence of a relationship between the gut microbiome and patients' response to immunotherapy, although Dr Derosa described her group's study as the first to show a negative effect of antibiotics on immunotherapy response.

Further studies "are warranted to investigate whether the alteration of the microbiota compositions is responsible for this different outcome," Dr Derosa concluded.

The study's importance may extend to other cancer types, she suggested in a press statement.

This research may be relevant to more than just kidney cancers. Dr Lisa Derosa

"This research may be relevant to more than just kidney cancers, as antibiotics are commonly prescribed to patients with cancer to prevent or treat infections related to cancer treatment or weakened immune system," Dr Derosa commented.

Study Details

The 80 patients with mRCC in the study were all enrolled in prospective clinical trials of immune checkpoint inhibitors. Overall, the patients were treated with either single-agent PD-1 or PD-L1 inhibitors, combinations of a PD-1 inhibitor and a CTLA-4 inhibitor, or combinations of a PD-L1 inhibitor and bevacizumab (Avastin, Genentech).

Most of the patients (78%) were treated with nivolumab (Opdivo, Bristol-Meyers Squibb), either alone or in combination with the CTLA-4 inhibitor ipilimumab (Yervoy, Bristol-Meyers Squibb).

Most of the patients were male (65%), had cancers with clear-cell histology (88%), and had undergone prior nephrectomy (80%). With regard to International Metastatic Renal Cell Carcinoma Database Consortium risk groups, 21%, 57%, and 22% had favorable, intermediate, and poor-risk disease, respectively.

The objective response rate was inferior among the patients who used antibiotics, and there was a trend toward decreased survival in those patients.

This study was supported by grants from the Philanthropia Foundation. Multiple study authors have financial ties to industry, including Bristol-Myers Squibb and Roche/Genentech.

Genitourinary Cancers Symposium (GUCS) 2017. Abstract 462, to be presented February 18, 2017.

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