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Safety evaluation of TOPAZ-1 and KEYNOTE-966 regimens in metastatic biliary tract cancer: a systematic review and meta-analysis.

29 June 2026·1 min read·Clinical & experimental metastasis

Abstract / Summary

The addition of immunotherapy to chemotherapy has improved prognosis of metastatic biliary tract cancer (BTC). The present systematic review aimed to assess frequency of treatment-emergent adverse events (TEAEs) among metastatic BTC patients receiving first-line immune checkpoint inhibitors (ICIs) plus chemotherapy in the two practice-changing TOPAZ-1 and KEYNOTE-966 clinical trials. The present systematic review and meta-analysis was recorded in the PROSPERO register with no. CRD420251137398. Incidence of TEAEs in patients receiving ICIs plus chemotherapy and in patients treated with placebo plus chemotherapy was collected. A total of two studies were included in these analyses including 1754 patients, comprising 1743 observations and 193 events for Grade 1/2 and 650 events for Grade ≥ 3. The risk of several TEAEs did not significantly differ between patients receiving chemoimmunotherapy versus those treated with chemotherapy alone. The present meta-analysis further confirms the tolerable safety profile of TOPAZ-1 and KEYNOTE-966 regimens as first-line therapy in advanced BTC. Future research should focus on identifying risk factors for TEAEs and develop prophylactic strategies to mitigate this risk without blunting antitumor efficacy. By improving our understanding and management of TEAEs, we might maximize the clinical benefits of ICIs and minimize harm, ultimately enhance clinical outcomes for BTC patients.

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Clinical & experimental metastasis

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