Results of the randomized, double-blind, global, phase 3 TOPAZ-1 trial (NCT03875235) demonstrated that the first-line chemoimmunotherapy regimen of the PD-L1 inhibitor durvalumab plus gemcitabine/cisplatin (GemCis; median follow-up, 13.7 months) significantly improved overall survival (OS) versus placebo plus GemCis (median follow-up, 12.6 months).1 Given that disease status at baseline may impact response to treatment in patients with biliary tract cancers (BTCs), an exploratory subgroup analysis of the TOPAZ-1 study was conducted to assess efficacy outcomes by disease status at baseline (initially unresectable vs recurrent [>6 months after surgery with curative intent or >6 months after adjuvant therapy]) in patients receiving GemCis plus durvalumab or placebo. These results were presented at the 2022 ESMO GI meeting.
Eligible patients with BTC were randomly assigned 1:1 to receive durvalumab (1500 mg) or placebo on day 1 every 3 weeks plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) on days 1 and 8 every 3 weeks for up to 8 cycles, followed by durvalumab or placebo monotherapy until disease progression, unacceptable toxicity, or discontinuation. Stratification was by disease status (initially unresectable vs recurrent) and primary tumor location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer). Efficacy outcomes assessed included OS, progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) per RECIST version 1.1.
A total of 685 patients were randomly assigned to durvalumab or placebo plus GemCis. A higher proportion of these patients had initially unresectable disease at baseline (n = 553) than recurrent disease (n = 131). Among patients with initially unresectable disease, baseline characteristics were generally well-balanced between treatment arms. Among patients with recurrent disease, the majority of patients were enrolled in Asia and had extrahepatic disease and metastatic disease.
OS hazard ratios (HRs) and PFS HRs favored durvalumab versus placebo in both initially unresectable (OS HR, 0.84; PFS HR, 0.79) and recurrent (OS HR, 0.56; PFS HR, 0.63) disease. Odds ratios (ORs) for ORR favored durvalumab versus placebo for both initially unresectable (OR, 1.61) and recurrent (OR, 1.52) disease. The median DOR was longer for durvalumab versus placebo irrespective of disease status at baseline. Consistently, the percentage of responders with a DOR ≥9 and ≥12 months was numerically higher with durvalumab versus placebo regardless of disease status at baseline. Fewer durvalumab-treated patients received subsequent anticancer therapy versus those who received placebo.
The results of the TOPAZ-1 study subgroup analysis by disease status at baseline indicated that “the addition of durvalumab to GemCis improved efficacy outcomes both in patients with initially unresectable and patients with recurrent disease at baseline, though the relative benefit versus placebo appears greater for recurrent compared with initially unresectable disease. These findings support the use of durvalumab plus GemCis as a potential new treatment option for patients with advanced BTC, irrespective of disease status.”
Source: Okusaka T, Kitano M, Chen M-H, et al. Outcomes by disease status in patients with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study. Abstract PD-8.
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