MIAMI — A stool bacteriomic profile may play a role in predicting response to sunitinib (Sutent) in patients with metastatic renal cell carcinoma (mRCC), researchers said here.
In four mRCC patients, those whose stool bacteria harbored an abundance of bacteroides were more likely to response to treatment with the checkpoint inhibitor, while those whose stool contained an abundance of bifidobacterium were more likely to experience disease progression despite sunitinib treatment, according to Nazli Dizman, MD, of the City of Hope in Duarte, California, and colleagues at the International Kidney Cancer Symposium.
While the findings are “very preliminary [and] … limited by sample size, we identified a discrepancy in stool bacteriomic distribution between response and progression in patients with metastatic disease,” Dizman stated.
“Further efforts to assess the link between microbiota and response to vascular endothelial growth-factor targeted therapies is warranted,” the authors wrote.
For the study, stool samples from mRCC patients scheduled for sunitinib treatment were collected at baseline, and weeks 2, 3, 4 and 12 of treatment. Response to therapy was assessed with RECIST 1.1 criteria after 3 months of treatment. For the stool bacteriomic profile, microbial DNA was extracted, and 16 RNA genetags were generated by PCR amplification and sequenced using MISeq. Sequence reads were assembled in operational taxonomic units (OTU).
All of the patients (three men; one woman) were non-Hispanic white. Two showed partial response to treatment while two had progressive disease.
“Stool bacteriomic profiling shows that 25,304 OTUs were attributed to 165 genera from 8 phyla,” the authors explained.
Dizman said the study is ongoing, and that another study with nivolumab (Opdivo) is underway at her institution.
In a second RCC study, antibiotic use 30 days prior to the first injection of checkpoint inhibitors negatively influenced outcomes, according to Lisa Derosa, MD, PhD, of the Gustave Roussy Cancer Center in Villejuif, France, and colleagues.
Her group conducted a retrospective analysis of 120 RCC patients, 13% of whom received antibiotics within 30 days of starting PD-L1 therapy. The majority (82%) received beta-lactamases. In the antibiotics group, patients were more likely to have larger tumors and have undergone two or more prior lines of therapy.
They reported the following in patients who had taken antibiotics in the 30 days prior to treatment:
- Increased rate of primary progressive disease: 75% vs 22% in patients who had not taken antibiotics (P<0.01)
- Shorter median progression-free survival (PFS): 1.9 vs 7.4 months (hazard ratio 3.13, 95% CI 1.42-6.89, P<0.01)
- Shorter median overall survival (OS): 17.3 vs 30.6 months (HR 3.48, 95% CI 1.11-10.80, P=0.03)
“Taking into account prognostic features relevant to RCC, both [antibiotics] and tumor burden were significantly associated with worse PFS and OS as univariates, so were carried into multivariate modeling,” the authors stated. “[Antibiotics] and tumor burden remained independently associated with worse PFS in multivariate analysis (HR 2.2, P<0.01), while neither variable remained significant for OS (HR 2.05, P=0.11).”
They suggested that antibiotics “represent a novel predictor of resistance independent from classical prognostic factors.”
Dizman and Derosa disclosed no relevant relationships with industry.