Pertuzumab and Trastuzumab in Previously Treated Patients With HER2-Positive Metastatic Biliary Tract Cancer

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As reported in The Lancet Oncology by Milind Javle, MD, and colleagues, findings in a cohort of the phase IIa MyPathway multiple basket study showed that the combination of pertuzumab and trastuzumab produced responses in some previously treated patients with HER2-positive metastatic biliary tract cancer.

The MyPathway study is evaluating the activity of U.S. Food and Drug Administration–approved therapies in nonindicated tumors with potentially actionable molecular alterations.

Milind Javle, MD

Milind Javle, MD

Study Details

In the U.S. multicenter trial, 39 patients with HER2 amplification, HER2 overexpression, or both were enrolled between October 2014 and May 2019. They received pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks plus trastuzumab at a loading dose of 8 mg/kg followed by 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

Patients had received a median of two prior treatment regimens. The primary endpoint was investigator-assessed objective response rate.


At data cutoff (March 2020), median follow-up was 8.1 months (interquartile range = 2.7–15.7 months). Objective responses—all partial—were observed in 9 patients (23%, 95% confidence interval [CI] = 11%–39%). An additional 11 patients (28%) had stable disease for 4 months or longer, yielding a disease control rate of 51%.

The most common tumor location was in the gallbladder, in 16 patients; objective response was observed in 5 (31%) and stable disease for 4 months or longer was also observed in 5 (31%) of these patients. Median duration of response was 10.8 months (95% CI = 0.7–25.4 months).

Median progression-free survival was 4.0 months (95% CI = 1.8–5.7 months). Median overall survival was 10.9 months (95% CI = 5.2–15.6 months), with an estimated 1-year rate of 50% (95% CI = 33%–64%).


  • Pertuzumab plus trastuzumab produced objective response in 23% of patients and disease control in 51%.
  • The median duration of response was 10.8 months.

Adverse Events

Grade 3 or 4 adverse events occurred in 46% of patients, the most commonly reported being increased alanine aminotransferase (13%) and increased aspartate aminotransferase (13%). Of these, grade 3 adverse events considered related to treatment occurred in three patients (8%).

Serious adverse events occurred in 26% of patients, with the only event occurring in more than one patient being abdominal pain (5%); no serious adverse events were considered related to treatment. No cardiac events were observed, and no deaths due to adverse events were observed.

The investigators concluded, “Treatment was well tolerated in patients with previously treated HER2-positive metastatic biliary tract cancer. The response rate is promising for the initiation of randomized, controlled trials of pertuzumab plus trastuzumab in this patient population.”

Dr. Javle, of the Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by F. Hoffmann-La Roche–Genentech. For full disclosures of the study authors, visit

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