Response rates and overall survival (OS), on the other hand, did not seem to be affected by antibiotic administration, according to investigator Petros Fessas, MD, of Imperial College London.
Dr. Fessas and colleagues presented these findings in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract 485).
Dr. Fessas noted that, in other cancers, antibiotics have been shown to reduce both response and survival rates after ICI.
To assess the impact of early antibiotic exposure on ICI efficacy in HCC, Dr. Fessas and colleagues examined data from 449 patients treated at 12 centers in the United States, Europe, and Asia.
The patients’ median age was 65 years, and 79.1% were men. Nearly three-quarters (73.3%) were cirrhotic (60.4% because of viral hepatitis), 79.9% were Child-Pugh class A, 72.4% were Barcelona Clinic Liver Cancer stage C, and 79% had an Eastern Cooperative Oncology Group performance status of 0-1.
Response and survival results
The investigators compared outcomes between patients with and without antibiotic exposure in the early immunotherapy period (EIOP) 30 days before and after ICI initiation.
In all, 170 patients (37.9%) received antibiotics in the EIOP. There were no differences in response rates, disease control rates, or median OS between patients who received antibiotics and those who did not.
The objective response rate was 20.2% in patients who received antibiotics in the EIOP and 16.1% in patients who did not (P = .2808). Disease control rates were 63.1% and 55.4%, respectively (P = .1144). The median OS was 15.3 months and 15.4 months, respectively (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21; P = .6275).
The median PFS, however, was significantly longer in patients who received antibiotics than in patients who did not – 6.1 months and 3.7 months, respectively (HR, 0.74; 95% CI, 0.60-0.93; P = .0135).
To overcome possible bias introduced by misclassification of patients who received antibiotics but discontinued immunotherapy within 30 days of initiation, the investigators conducted a landmark selection analysis among only those patients with a median follow-up for PFS of 30 days or longer (n = 402). This analysis confirmed the prior findings.
“Antibiotic exposure in the 30 days before or after immune checkpoint initiation in hepatocellular carcinoma is associated with prolonged progression-free survival,” Dr. Fessas concluded.
He added that a key question for future research is to discover the immune-microbiologic determinants of response to initiation of ICIs.
Positive effect surprising
“My group has shown that antibiotic therapy is normally detrimental in patients with cancer,” investigator David J. Pinato, MD, PhD, of Imperial College London, said in an interview. “So we were very surprised to see a positive effect on PFS.”
He added that the new findings should be interpreted with caution.
“My feeling is that, unlike with many other malignancies, the gut microbiome is heavily involved in the progression of the cirrhosis that pre-dates HCC onset,” he said.
That would suggest the relationship between antibiotics and perturbation of the gut microbiome is dictated by something more than changes in antitumor immune tolerance, he added.
“Overall, I think the interplay is more complex in HCC: cirrhosis/cancer/microbiome, not just microbiome/cancer as in many other tumors,” Dr. Pinato said. “So we are looking at microbial determinants of response in HCC patients undergoing ICI therapy, and we are hopeful to see some more mechanistic evidence behind this association.”
Dr. Pinato disclosed relationships with ViiV Healthcare, Bayer Healthcare, Bristol Myers Squibb, Mina Therapeutics, Eisai, Roche, and AstraZeneca. Dr. Fessas reported having no conflicts of interest. No funding source for the study was disclosed.