Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The
José Enrique Alés-Martínez1, Judith Balmaña2, Pedro Sánchez-Rovira3
1Hospital Nuestra Sra. De Sonsoles, Ávila, Spain.
Purpose:
To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm).
Methods:
OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged ≥18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in BRCA1 or BRCA2 who had received at least one prior systemic regimen for advanced disease were enrolled. Patients received olaparib plus trastuzumab until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was investigator-assessed clinical benefit rate for at least 24 weeks as per RECIST v.1.1. Key secondary endpoints included overall response rate (ORR) and safety profile.
Results:
A total of 68 pre-treated HER2-positive ABC patients were screened. Due to slow accrual the trial was stopped after enrolling 5 patients instead of the planned sample size of 20. Four patients achieved clinical benefit (80.0 %, 95 % CI; 28.4-99.5, p < 0.001) and the primary endpoint was met. The ORR was 60.0 % (95 % CI; 14.7-94.7), including one complete response. Four (80.0 %) patients experienced at least one treatment-related treatment-emergent adverse event (TEAE). Most TEAEs were grade 1 or 2. There were no treatment-related deaths and no new safety signals were identified.
Conclusions:
This study suggests that the combination of olaparib plus trastuzumab may be effective and safe in pre-treated patients with HER2-positive gBRCAm ABC. This ABC patient population should be further studied and not be pre-emptively excluded from clinical trials of targeted therapy for BRCA1/2-driven cancers.
Insights
The combination of olaparib and trastuzumab showed promising efficacy and safety in HER2-positive advanced breast cancer patients with BRCA mutations. Further research is warranted for this targeted therapy in BRCA1/2-driven cancers.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- HER2-positive advanced breast cancer (ABC) with germinal BRCA mutations (gBRCAm) represents a distinct subtype.
- Targeted therapies are crucial for improving outcomes in this patient population.
- The combination of olaparib and trastuzumab is being investigated for its potential synergistic effects.
Purpose of the Study:
- To evaluate the efficacy and safety of olaparib plus trastuzumab in patients with HER2-positive ABC and gBRCAm.
- To determine the clinical benefit rate and overall response rate (ORR) of this combination therapy.
- To assess the safety profile and identify any treatment-related adverse events.
Main Methods:
- The OPHELIA trial (NCT03931551) was a single-arm, open-label, phase 2 clinical study.
- Patients with HER2-positive ABC and germinal deleterious BRCA1 or BRCA2 mutations, pre-treated with at least one systemic regimen, were enrolled.
- Treatment consisted of olaparib plus trastuzumab until disease progression, unacceptable toxicity, or withdrawal of consent.
Main Results:
- The primary endpoint of clinical benefit rate for at least 24 weeks was met in 80.0% of the 5 enrolled patients (95% CI; 28.4-99.5).
- The overall response rate (ORR) was 60.0% (95% CI; 14.7-94.7), including one complete response.
- Four patients (80.0%) experienced treatment-related adverse events, mostly grade 1 or 2, with no treatment-related deaths or new safety signals.
Conclusions:
- The combination of olaparib plus trastuzumab demonstrates potential efficacy and a favorable safety profile in pre-treated HER2-positive gBRCAm ABC.
- This patient population should not be excluded from trials investigating targeted therapies for BRCA1/2-driven cancers.
- Further studies are recommended to confirm these findings in a larger cohort.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...