Results of an ongoing, phase 2a, multiple-basket study (MyPathway) showed that dual HER2-targeted therapy with pertuzumab plus trastuzumab was well-tolerated in patients with previously treated HER2-positive metastatic biliary tract cancer.
The ongoing, nonrandomized, multicenter, open-label, phase 2a, multiple-basket study (MyPathway; ClinicalTrials.gov Identifier: NCT02091141) evaluated the activity of approved therapies in nonindicated tumors with potentially actionable molecular alterations. Results of the metastatic biliary tract cancer (BTC) cohort with HER2 amplification and/or overexpression that received the dual anti-HER2 inhibitors pertuzumab and trastuzumab were published in The Lancet Oncology in April 2021.
The study enrolled patients aged ≥18 years with previously treated metastatic BTC with HER2 amplification and/or overexpression and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2, between October 28, 2014, and May 29, 2019. Eligible patients received intravenous (IV) pertuzumab (840-mg loading dose, then 420 mg every 3 weeks) plus IV trastuzumab (8-mg/kg loading dose, then 6 mg/kg every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST version 1.1. Secondary end points included clinical benefit ratio (ie, the percentage of patients with an objective response or stable disease [SD] for >4 months), disease control rate, duration of response (DOR), progression-free response (PFS), overall survival (OS), rate of OS at 1 year, safety, and tolerability. The data cutoff date was March 10, 2020.
Of the 661 patients enrolled in MyPathway, 39 participants had HER2-positive BTC and had received ≥1 doses of pertuzumab plus trastuzumab. Of the 39 patients in the BTC cohort, 32 discontinued treatment, 4 more discontinued but remained in follow-up, whereas 3 remained on treatment. All 39 patients received pertuzumab plus trastuzumab for a median of 3.5 months. The median age of the study population was 68 years; the majority of participants (59%) had an ECOG PS of 1 and had HER2 amplification with overexpression status unknown (80%). In terms of tumor location, 16 patients had gallbladder cancer, 7 had intrahepatic cholangiocarcinoma (CCA), 7 had extrahepatic CCA, and 5 had ampulla. A total of 16 patients had received 1 prior regimen, 8 had received 2 previous regimens, and 9 had received 3 prior regimens; 62% had received prior gemcitabine/cisplatin therapy.
At a median follow-up of 8.1 months, an ORR of 23% was achieved, all of which were partial responses. Disease control was achieved in 51% of participants, with SD attained by an additional 11 patients. The median DOR among responders was 10.8 months. The median PFS was 4.0 months, and the median OS was 10.9 months. At 1 year, the estimated OS was 50%.
In the safety population (n = 39), grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 46% of patients. The most common TEAEs were increased alanine aminotransferase (ALT) and increased aspartate aminotransferase (AST), both of which were reported in 13% of the participants. Grade 3 treatment-related adverse events (TRAEs) were reported in 3 patients, including increased ALT, AST, blood alkaline phosphatase, and blood bilirubin. Serious TEAEs occurred in 10 patients; no serious TRAEs, grade 4 TRAEs, or deaths were reported.
Overall, based on these results, the investigators concluded that dual HER inhibition with pertuzumab plus trastuzumab was well-tolerated in patients with previously treated HER2-positive metastatic BTC, warranting further evaluation in randomized, controlled trials in this patient population.
Source: Javle M, Borad MJ, Azad NS, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2021;22:1290-1300.
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