Use of antibiotics safe during durvalumab-based treatment for biliary tract cancer
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Patients with advanced biliary tract cancer can safely use antibiotics while benefiting from treatment with durvalumab plus gemcitabine and cisplatin, according to study results presented at ASCO Gastrointestinal Cancers Symposium.
The subgroup analysis of the phase 3 TOPAZ-1 study showed no meaningful difference in OS or PFS among patients who received antibiotics and those who did not during durvalumab-based chemotherapy.
Background
Patients with biliary tract cancer often receive antibiotics to treat infection that occurs as a result of biliary tract obstruction, Aiwu Ruth He, MD, PhD, associate professor in the division of hematology and oncology at Georgetown Lombardi Comprehensive Cancer Center, told Healio. However, previous research has shown use of antibiotics during cancer treatment with immune checkpoint inhibitors to be associated with shorter PFS and OS.
The primary analysis of the TOPAZ-1 study showed the addition of the immune checkpoint inhibitor durvalumab (Imfinzi, AstraZeneca) to gemcitabine and cisplatin significantly prolonged OS compared with placebo plus gemcitabine and cisplatin (HR = 0.8; 95% CI, 0.66-0.97), with manageable toxicity. Based on the results, the combination received FDA approval in September for adults with locally advanced or metastatic biliary tract cancer.
“Here, we performed an analysis of participants with advanced biliary tract cancer who received antibiotics at the same time as treatment with durvalumab plus gemcitabine and cisplatin or placebo plus gemcitabine and cisplatin in the TOPAZ-1 study,” He told Healio.
Methodology
Among the 685 patients in TOPAZ-1, 54 (15.8%) in the durvalumab group and 76 (22.1%) in the placebo group received one or more doses of antibiotics within 14 days of the first dose of treatment (baseline use), and 167 patients in each group (49% and 48.5%) received at least one dose 14 days before first treatment dose to 14 days after the last treatment dose (concomitant use).
The most common adverse events that led to baseline antibiotic use included cholangitis and pyrexia, whereas pyrexia, cholangitis and urinary tract infections most often led to concomitant antibiotic use.
Data cutoff for OS analyses occurred on Feb. 25, 2022, and included 6.5 months of additional follow-up after the primary data cutoff.
Results
Durvalumab plus chemotherapy conferred an OS benefit among all patients who received antibiotics (HR = 0.76; 95% CI, 0.64-0.91), including patients who received them at baseline (HR = 0.83; 95% CI, 0.56-1.22) and those who did not (HR = 0.79; 95% CI, 0.65-0.96), as well as those who received concomitant antibiotics (HR = 0.72; 95% CI, 0.57-0.92) and those who did not (HR = 0.83; 95% CI, 0.65-1.06).
HRs for PFS at the primary data cutoff also favored the durvalumab vs. placebo regimen among all antibiotics users (HR = 0.75; 95% CI, 0.63-0.89), users at baseline (HR = 0.73; 95% CI, 0.49-1.06), nonusers at baseline (HR = 0.79; 95% CI, 0.66-0.95), concomitant users (HR = 0.7; 95% CI, 0.55-0.89) and those with no concomitant use (HR = 0.82; 95% CI, 0.65-1.03).
Implications
The results support use of antibiotics during treatment with durvalumab and chemotherapy when clinically indicated, according to researchers.
“It is good to know from this subgroup analysis that for patients with advanced biliary tract cancer, risk [for] death and the risk that their cancer would grow, spread or get worse was not meaningfully different between patients who used antibiotics and those who did not use antibiotics at the same time as they were receiving durvalumab-based treatment,” He told Healio. “We need to understand why use of antibiotics during treatment with immunotherapy is correlated with poor outcome in some circumstances but not correlated with poor outcome in other circumstances.”
References:
- He AW, et al. Poster 550. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 19-21, 2023; San Francisco.
- Jiang S, et al. Front Oncol. 2022;doi:10.3389/fonc.2022.823705.
- Oh D-Y, et al. NEJM Evid. 2022;doi:10.1056/EVIDoa2200015.
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He AW, et al. Abstract 550. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 19-21, 2023; San Francisco.
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