Pertuzumab and Trastuzumab in Patients With ERBB2/3-Altered Urothelial or Ovary/Fallopian Tube Cancer: Results From the Targeted Agent and Profiling Utilization Registry Study
John K Chan1, Michael Rothe2, Elizabeth Garrett-Mayer2
1Sutter Cancer Research Consortium, San Francisco, CA.
Purpose:
TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations. Results of two cohorts of patients with urothelial (UC) or ovarian/fallopian tube cancer (OC/FTC) with ERBB2/3 alterations treated with pertuzumab plus trastuzumab (P + T) are reported.
Methods:
Eligible patients had advanced cancer, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with ERBB2/3 alterations, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration. Simon's two-stage design is based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety.
Results:
Patients with UC (n = 28) or OC/FTC (n = 25) with ERBB2/3 alterations were enrolled from March 2017 to June 2023. In the UC cohort, the DC and OR rates were 37% (90% CI, 24 to 100) and 25% (95% CI, 11 to 45), respectively. The null hypothesis of 15% DC rate was rejected (P = .005). In the OC/FTC cancer cohort, the DC and OR rates were 23% (90% CI, 9 to 100) and 8% (95% CI, 1 to 26), respectively. The null hypothesis of 15% DC rate was not rejected (P = .35). Six patients had at least one grade 3-5 adverse event (AE) or serious AE at least possibly related to treatment.
Conclusion:
The combination of P + T met prespecified criteria to declare a signal of activity in patients with UC with ERBB2/3 alterations, but not in patients with OC/FTC.
Insights
Pertuzumab plus trastuzumab showed antitumor activity in urothelial cancer (UC) patients with ERBB2/3 alterations. The combination did not meet activity criteria in ovarian/fallopian tube cancer (OC/FTC) patients.
Area of Science:
- Oncology
- Genomic Medicine
- Clinical Trials
Background:
- The TAPUR trial assesses targeted agents in advanced cancers with specific genomic alterations.
- ERBB2/3 alterations are implicated in various advanced cancers, including urothelial and ovarian/fallopian tube cancers.
Purpose of the Study:
- To evaluate the antitumor activity of pertuzumab plus trastuzumab (P + T) in patients with advanced urothelial cancer (UC) or ovarian/fallopian tube cancer (OC/FTC) harboring ERBB2/3 alterations.
- To determine if the combination therapy meets predefined criteria for disease control.
Main Methods:
- A phase II basket trial design (TAPUR) was employed.
- Patients with advanced UC (n=28) or OC/FTC (n=25) and ERBB2/3 alterations received P + T.
- Disease control (DC), defined as objective response (OR) or stable disease (SD) for ≥16 weeks, was the primary endpoint.
Main Results:
- In the UC cohort, the DC rate was 37% (P=0.005), meeting the primary endpoint.
- In the OC/FTC cohort, the DC rate was 23% (P=0.35), not meeting the primary endpoint.
- Adverse events possibly related to treatment were observed in six patients.
Conclusions:
- Pertuzumab plus trastuzumab demonstrated a signal of activity in advanced UC with ERBB2/3 alterations.
- The combination did not show significant activity in advanced OC/FTC with ERBB2/3 alterations based on the study's criteria.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
02:56Treatment Resistant Cancers