![]() ![]() Oh and colleagues designed the randomized, double-blind, placebo-controlled, phase 3 TOPAZ-1 trial to confirm whether adding durvalumab to chemotherapy confers meaningful benefits. 2īased on encouraging antitumor activity observed with durvalumab plus gemcitabine and cisplatin in a phase 2 trial, Dr. Based on encouraging antitumor activity observed with durvalumab plus gemcitabine and cisplatin in a phase 2 trial, Dr. ![]() Upon recognizing that BTCs display immunogenic features, investigators have increasingly explored immune checkpoint inhibitors as possible options for enhancing disease control and prolonging survival. For example, patients who receive first-line gemcitabine and cisplatin usually do not live beyond 12 months. For more than a decade, chemotherapy has been the best first- and second-line treatment option for patients with BTCs, even though responses are typically transient. TOPAZ-1 Rationale and DesignīTCs comprise a heterogeneous collection of rare, aggressive neoplasms, which together carry a very poor prognosis. Oh noted that these toxicities are consistent with those typically observed with gemcitabine and cisplatin. The most common all-grade TRAEs observed in the durvalumab arm were hematologic events, such as anemia (48.2%) and neutropenia (31.7%), along with nausea (40.2%). Likewise, similar proportions of patients treated with durvalumab and those treated with placebo discontinued study medication due to TRAEs (8.9% vs 11.4%), with a slight advantage in favor of durvalumab. There was little difference in the incidence of grade 3/4 treatment-related adverse events (TRAEs) between patients who received durvalumab and those who received placebo (62.7% vs 64.9%). In terms of safety, durvalumab proved to be well tolerated when combined with chemotherapy. “It will be important to look at the subset analyses to try to determine if there are particular patients who will benefit or not benefit from this strategy so that we can really tailor treatment going forward,” Dr. In addition, separation between the survival curves widened over time, also consistent with the sustained survival benefits often achieved with immune checkpoint inhibitors in a subset of patients. Oh said is consistent with many other phase 3 clinical trials comparing immune checkpoint inhibitor/chemotherapy combinations against chemotherapy alone. Of note, separation in the survival curves for the 2 treatment arms did not occur until about 6 months after treatment initiation, which Dr. 001), as was the objective response rate (26.7% vs 18.7%). Progression-free survival was also greatly improved with chemoimmunotherapy vs chemotherapy alone (HR 0.75, 95% CI P =. Accordingly, it is likely to become the new standard of care for first-line therapy for many-if not the majority-of patients,” said Nilofer Azad, MD, of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, who served as the discussant for the abstract.Īt the first interim analysis, treatment with durvalumab plus gemcitabine and cisplatin conferred a 20% reduction in the risk of death compared with gemcitabine and cisplatin alone, thus meeting the primary endpoint of the trial (HR 0.80, 95% CI P =. “This is the first trial in over a decade that has shown a survival benefit with the addition of another agent to gemcitabine and cisplatin. Principal investigator Do-Youn Oh, MD, PhD, of Seoul National University Hospital and Seoul National University College of Medicine, presented the study findings at the 2022 ASCO Gastrointestinal Cancers Symposium. TOPAZ-1, the first global phase 3 study to evaluate use of immunotherapy in the first-line setting in advanced biliary tract cancers (BTCs), demonstrated that adding the PD-L1 inhibitor durvalumab to gemcitabine and cisplatin-the current first-line standard of care-significantly improves overall survival and other efficacy outcomes without exacerbating toxicity ( Abstract 378). Adding durvalumab to gemcitabine and cisplatin significantly improved overall survival, progression-free survival, and objective response rate, without exacerbating toxicity.TOPAZ-1 represents the first phase 3 trial to demonstrate positive results with the addition of an immune checkpoint inhibitor to standard first-line chemotherapy in biliary tract cancer. ![]()
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