Study at-a-Glance
- Focus: The study explores the efficacy and safety of the combination therapy of pertuzumab plus trastuzumab in patients with advanced biliary tract cancer (BTC) harboring ERBB2/3 alterations. BTC includes gallbladder cancer, cholangiocarcinoma, and ampullary adenocarcinoma.
- Population: 29 patients with advanced BTC were included, with a median age of 66 years (range: 34-83). 66% were female, and 52% identified as White, 21% as Black or African American, and 10% as Asian/Asian American.
- Main Takeaway: The study found that pertuzumab plus trastuzumab met the prespecified criteria to declare a signal of activity in patients with advanced BTC and ERBB2/3 alterations, providing an objective response rate (ORR) of 32% and a disease control rate (DCR) of 40%.
- Significance: This combination therapy demonstrates notable clinical activity for heavily pretreated patients with BTC, showing potential in managing disease progression in those with ERBB2/3 amplification, overexpression, or mutation.
A new study, published May 15, 2024 in the Journal of Clinical Oncology (JCO), shows encouraging results for the combination therapy of pertuzumab and trastuzumab in treating advanced biliary tract cancer (BTC) with ERBB2/3 alterations. The incidence and mortality rates of BTC have risen significantly in recent years, with a 5-year survival rate of only 2% for patients with metastatic disease. The article is titled “Pertuzumab Plus Trastuzumab in Patients With Biliary Tract Cancer With ERBB2/3 Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.”
“Our study highlights the significance of comprehensive genomic profiling in identifying viable treatment options for biliary tract cancers, a field where recent advances have dramatically changed the therapeutic landscape. With up to 19% of gallbladder cancers and 17% of extrahepatic cholangiocarcinomas harboring ERBB2 amplifications, our findings underscore the efficacy of the pertuzumab and trastuzumab combination in these patients. This therapy, already recommended in the NCCN guidelines as a category 2A treatment, now has further support from our TAPUR study data. This encourages not just routine genomic profiling of BTC tumors to detect alterations targeted by FDA approved drugs, but underscores the importance of informed discussions between patients and their oncologists about targeted therapies that may not have been previously considered,” said study principal investigator Dr. Richard L. Schilsky, MD, Professor Emeritus at University of Chicago and former ASCO Executive Vice President and Chief Medical Officer.
About the Study
The Targeted Agent and Profiling Utilization Registry (TAPURTM) Study is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer. This cohort study focused on patients with advanced BTC and ERBB2/3 genomic alterations. All participants had an ECOG performance status of 0-2, indicating varying levels of daily functioning. Of the 29 enrolled patients, 28 were evaluable for efficacy. The primary endpoint was disease control (objective response or stable disease for at least 16 weeks), while secondary endpoints included objective response, progression-free survival, overall survival, and adverse events.
Patients received pertuzumab and trastuzumab intravenously every three weeks until evidence of disease progression or discontinuation due to toxicity or patient preference.
Key Findings
- One complete response, eight partial responses, and two cases of stable disease for at least 16 weeks were observed, resulting in a DCR of 40% and an ORR of 32%.
- Four patients experienced grade 3 adverse events possibly related to treatment: anemia, diarrhea, infusion reaction, and fatigue.
- The therapy met the criteria for a statistically significant signal of activity, indicating its efficacy in this subset of BTC patients.
Next Steps
New ERBB2-directed therapies will be evaluated in the upcoming year, with a focus on antibody-drug conjugates that have shown promising results in a variety of solid tumors featuring ERBB2 alterations. Notably, one such therapy has recently received histology-agnostic FDA approval for use in any solid tumor with 3+ ERBB2 overexpression according to immunohistochemistry. The team plans to include these advanced treatments in the TAPUR study, assessing their effectiveness both as individual treatments and in combination with other therapeutic agents.
Funding
Pertuzumab and trastuzumab and funding were provided by Genentech. Additional funding for the TAPUR Study came from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Merck, Pfizer, Seagen, now a wholly owned subsidiary of Pfizer Inc, and Taiho Oncology.
ASCO Perspective
“The findings from the ASCO-sponsored TAPUR basket trial further validates the very promising role of the ERBB2/3 pathway in the treatment of advanced biliary tract carcinoma, with the combination of pertuzumab plus trastuzumab as a possible treatment option. These findings demonstrate the need for HER2 testing in this patient population,” said ASCO Expert Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center.