Promising Responses Observed in HER2+, Metastatic Biliary Tract Cancer Following Treatment With Pertuzumab and Trastuzumab


Patients with HER2-positive, metastatic biliary tract cancer experienced promising responses and a tolerable safety profile following treatment with pertuzumab plus trastuzumab.

Responses to pertuzumab (Perjeta) and trastuzumab (Herceptin) appeared promising, as well as being well-tolerated in a population of patients with HER2-positive, metastatic biliary tract cancer, according to results from the phase 2a MyPathway multiple basket study (NCT02091141) published in Lancet Oncology.

The objective response rate (ORR) among patients treated with the pertuzumab and trastuzumab combination as assessed by investigators according to RECIST version 1.1 criteria was 23% (95% CI, 11%-39%). Stable disease of more than 4 months was observed in 28% of patients (range, 4.2-22.7 months), which translated to an overall disease control rate (DCR) of 51%. Additionally, the median duration of response (DOR) was 10.8 months (95% CI, 0.7-25.4).

“Results from MyPathway indicate that pertuzumab plus trastuzumab, a chemotherapy-free regimen, has promising, durable activity in patients with HER2-positive metastatic biliary tract cancer, with good tolerability relative to traditional cytotoxic treatments,” the investigators wrote.

A 840 mg loading dose of pertuzumab was initially administered followed by a 420 mg dose of the agent every 3 weeks. A 8 mg/kg loading dose of trastuzumab was administered followed by a 6 mg/kg dose every 3 weeks. Both were administered intravenously until disease progression or unacceptable toxicity.

Patients who enrolled on the study needed to be 18 years or older with previously treated metastatic biliary tract cancer with HER2 amplification, overexpression, or both. Patients needed an ECOG performance status of 0 to 2 and a life expectancy of at least 12 weeks.

The study’s primary end point was investigator-assessed ORR via RECIST version 1.1 criteria. Key secondary end points were DCR, DOR, progression-free survival (PFS), median overall survival (OS), and safety and tolerability.

A total of 39 patients with HER2-positive biliary tract cancer were enrolled and were evaluable for anti-tumor activity as of the data cutoff point of March 10, 2020. At the data cutoff, 8% of patients remained on treatment, 10% had discontinued treatment while remaining in follow-up, and 82% discontinued treatment entirely. Progressive disease was the primary reason for treatment discontinuation (97%). The median follow-up was 8.1 months (Interquartile range, 2.7-15.7) from treatment initiation.

At the data cutoff, 92% and 74% of patients had progressed and died, respectively. Estimated median progression-free survival (PFS) was 4.0 months (95% CI, 1.8-5.7) and the estimated median overall survival (OS) was 10.9 months (95% CI, 5.2-15.6).

The HER2 alteration subgroup analyses indicated that in a population of patients with HER2 mutations plus amplifications or overexpression, 3 patients achieved a partial response, 1 had stable disease, and 2 had progressive disease.

The ORR was 20% for patients with HER2 amplification of the both tissue and blood and for patients with HER2 amplification in just tissue. The estimated PFS was 60% (95% CI, 25%-83%) at 3 months and 40% (95% CI, 12%-67%) at 6 months. Additionally, the ORR was 80% (95% CI, 20%-97%) at both time points for patients with HER2 amplification in the tissue only, respectively.

Treatment-emergent adverse effects (TEAEs) were observed in 92% of patients, the most common being diarrhea (33%), increased alanine aminotransferase (31%), and increased aspartate aminotransferase (31%). Forty-six percent of patients experienced grade 3/4 TEAEs. Common grade 3/4 AEs included increased alanine aminotransferase (13%) and increased aspartate aminotransferase (13%). Serious TEAEs were observed in 26% of patients.

Treatment-related AEs (TRAEs), defined as resulting from 1 or both treatments, were reported in 62% of patients and common included diarrhea (26%), increased alanine amino-transferase (10%), increased aspartate amino-transferase (10%), and infusion-related reaction (10%). Grade 3 TRAEs were reported in 3 patients, with the specific events including increased alanine amino-transferase, aspartate aminotransferase, blood alkaline phosphatase, and blood bilirubin. No cardiac, grade 4/5, or serious TRAEs were reported.

“We believe that our data support the consideration of pertuzumab plus trastuzumab as a treatment option in the second line and beyond, and are encouraging for the initiation of randomised, clinical trials to further explore the efficacy of this and other HER2-targeted regimens in this disease setting. Additional studies should also assess the role of HER2 overexpression in HER2-amplified biliary tract cancer and co-alterations that potentially confer resistance to HER2-targeted therapy, including KRAS and PIK3CA, which might affect real-world treatment choice,” the investigators concluded.


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(9):1290-1300. doi:10.1016/S1470-2045(21)00336-3

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