Pertuzumab Plus Trastuzumab in Patients With Endometrial Cancer With ERBB2/3 Amplification, Overexpression, or
Eugene R Ahn1, Michael Rothe2, Pam K Mangat2
1Cancer Treatment Centers of America-Chicago, part of City of Hope, Zion, IL.
Purpose:
The TAPUR Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with endometrial cancer (EC) with ERBB2 or ERBB3 (ERBB2/3) amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab (P + T) are reported.
Methods:
Eligible patients had advanced EC, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with ERBB2/3 amplification, overexpression, or mutation. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks (SD16+) duration. Secondary end points include safety, duration of response, duration of SD, progression-free survival (PFS), and overall survival (OS).
Results:
Twenty-eight patients were enrolled from March 2017 to November 2019; all patients were evaluable for efficacy and toxicity. Seventeen patients had tumors with ERBB2/3 amplification and/or overexpression, eight with both ERBB2 amplification and ERBB2/3 mutations, and three with only ERBB2 mutations. Ten patients had DC (two partial response and eight SD16+); all 10 had ERBB2 amplification, and 6 of the 10 patients with DC had >1 ERBB2/3 alteration. DC and OR rates were 37% (95% CI, 21 to 50) and 7% (95% CI, 1 to 24), respectively; the median PFS and median OS were 16 weeks (95% CI, 10-28) and 61 weeks (95% CI, 24-105), respectively. One patient experienced a grade 3 serious adverse event (muscle weakness) at least possibly related to P + T.
Conclusion:
P + T has antitumor activity in heavily pretreated patients with EC with ERBB2 amplification and warrants additional study.
Insights
Pertuzumab plus trastuzumab (P + T) demonstrated antitumor activity in patients with advanced endometrial cancer (EC) with ERBB2 amplification. This targeted therapy showed promise for heavily pretreated EC patients with specific genomic alterations.
Area of Science:
- Oncology
- Genomics
- Clinical Trials
Background:
- The TAPUR study is a pragmatic basket trial assessing targeted agents in advanced cancers.
- Endometrial cancer (EC) patients with specific genomic alterations were evaluated.
Purpose of the Study:
- To evaluate the antitumor activity of pertuzumab plus trastuzumab (P + T) in patients with advanced EC.
- To assess patients with ERBB2 or ERBB3 (ERBB2/3) amplification, overexpression, or mutation.
Main Methods:
- A cohort of 28 advanced EC patients with ERBB2/3 alterations were treated with P + T.
- Disease control (DC) was defined as objective response (OR) or stable disease (SD) of at least 16 weeks (SD16+).
- Secondary endpoints included safety, duration of response, progression-free survival (PFS), and overall survival (OS).
Main Results:
- Ten patients (37%) achieved disease control (DC), including two partial responses and eight SD16+.
- All patients with DC had ERBB2 amplification; 6 of 10 had multiple ERBB2/3 alterations.
- Median PFS was 16 weeks and median overall survival (OS) was 61 weeks. One grade 3 adverse event was reported.
Conclusions:
- Pertuzumab plus trastuzumab (P + T) exhibits antitumor activity in heavily pretreated endometrial cancer (EC) patients with ERBB2 amplification.
- The combination warrants further investigation in this patient population.
