Pertuzumab Plus Trastuzumab in Patients With Biliary Tract Cancer With ERBB2/3 Alterations: Results From the Targeted
Timothy L Cannon1, Michael Rothe2, Pam K Mangat2
1Inova Schar Cancer Institute, Fairfax, VA.
Purpose:
Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with biliary tract cancer (BTC) with ERBB2/3 amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab are reported.
Methods:
Eligible patients had advanced BTC, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with ERBB2/3 alterations, and a lack of standard treatment options. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16+ weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of stable disease, and safety.
Results:
Twenty-nine patients were enrolled from February 2017 to January 2022, and all had advanced BTC with an ERBB2/3 alteration. One patient was not evaluable for efficacy. One complete response, eight partial responses, and two SD16+ were observed for DC and OR rates of 40% (90% CI, 27 to 100) and 32% (95% CI, 16 to 52), respectively. The null hypothesis of 15% DC rate was rejected (P = .0015). Four patients had at least one grade 3 adverse event (AE) or serious AE at least possibly related to treatment: anemia, diarrhea, infusion-related reaction, and fatigue.
Conclusion:
Pertuzumab plus trastuzumab met prespecified criteria to declare a signal of activity in patients with BTC and ERBB2/3 amplification, overexpression, or mutation.
Insights
Pertuzumab plus trastuzumab showed activity in biliary tract cancer (BTC) patients with ERBB2/3 alterations. The combination therapy met prespecified criteria, indicating a potential treatment signal for this patient group.
Area of Science:
- Oncology
- Genomic Medicine
- Clinical Trials
Background:
- Biliary tract cancer (BTC) is an aggressive malignancy with limited treatment options.
- Targeted therapies offer potential for patients with specific genomic alterations.
- ERBB2/3 alterations are implicated in various cancers, including BTC.
Purpose of the Study:
- To evaluate the antitumor activity of pertuzumab plus trastuzumab in advanced BTC patients.
- To assess patients with ERBB2/3 amplification, overexpression, or mutation.
- To report results from a cohort within the Targeted Agent and Profiling Utilization Registry (TAPUR) trial.
Main Methods:
- Phase II basket trial enrolling patients with advanced BTC and ERBB2/3 alterations.
- Treatment with pertuzumab plus trastuzumab.
- Primary endpoint: disease control (objective response or stable disease ≥16 weeks) per RECIST v1.1.
Main Results:
- 29 patients with advanced BTC and ERBB2/3 alterations were enrolled.
- Disease control rate was 40% (90% CI, 27-100), with an objective response rate of 32%.
- The combination therapy met the primary endpoint, rejecting the null hypothesis of a 15% disease control rate (P = .0015).
Conclusions:
- Pertuzumab plus trastuzumab demonstrated a signal of activity in patients with BTC and ERBB2/3 alterations.
- The findings support further investigation of this combination in this specific patient population.
- The treatment was generally well-tolerated, with manageable adverse events.
