GALLEN, SWITZERLAND – The percentage of women veterans using VA medical facilities has increased 46% since 2005. One effect is that both the VA and MHS are treating far more breast cancer than ever before, especially since some recent studies suggest that women veterans are as much as 40% more likely to develop breast cancer than their civilian counterparts.
HER2 types, sometimes called ERBB2, are amplified and/or overexpressed in 20-30% of invasive breast carcinomas. A recent study looked at treating advanced cases without chemotherapy, noting that, for some patients with ERBB2-positive metastatic breast cancer, a chemotherapy-free strategy could be a viable option as first-line treatment.
That’s according to the secondary analysis of a randomized clinical trial. International researchers proposed using pertuzumab plus trastuzumab alone without chemotherapy as first-line treatment followed by trastuzumab plus emtansine at progression in ERBB2-positive (formerly HER2) metastatic breast cancer (MBC).
“Overall survival was not compromised by delaying chemotherapy to later treatment lines, despite a much shorter first-line [progression-free survival.],” the researchers wrote in JAMA Oncology. “Selecting these patients with ERBB2-enriched tumors according to their PAM50 signature did not enable us to identify the most appropriate population for de-escalation.”1
The question addressed was whether the regimen without chemotherapy would result in similar overall survival with fewer toxic effects and better quality of life compared with immediate chemotherapy.
Based on the analysis with 210, overall survival was found to be similar for both strategies at two years despite a longer progression-free survival observed with the addition of chemotherapy to trastuzumab and pertuzumab.
Currently, with ERBB2 (formerly HER2)-positive MBC combining trastuzumab and pertuzumab with taxane-based chemotherapy is the first line of standard care. “Given that trastuzumab plus pertuzumab was proven effective in ERBB2-positive MBC, even without chemotherapy, whether the optimal first-line strategy could be trastuzumab plus pertuzumab alone instead of with chemotherapy is unresolved,” the authors noted.
The original study leading to the secondary analysis was a multicenter, open-label, phase 2 randomized clinical trial conducted at 27 sites in France, 20 sites in Switzerland, 9 sites in the Netherlands, and 1 site in Germany. Researchers randomized 210 patients with centrally confirmed ERBB2-positive and a median age of 58 between May 3, 2013, and January 4, 2016, with termination of the trial May 26, 2020. Data were analyzed from December 18, 2020, to May 10, 2022.
In the trial, patients randomly received pertuzumab (840 mg intravenously [IV], then 420 mg IV every 3 weeks) plus trastuzumab (8 mg/kg IV, then 6 mg/kg IV every 3 weeks) without chemotherapy (group A) or pertuzumab plus trastuzumab (same doses) with either paclitaxel (90 mg/m2 for days 1, 8, and 15, then every 4 weeks for ≥4 months) or vinorelbine tartrate (25 mg/m2 for first administration followed by 30 mg/m2 on days 1 and 8 and every 3 weeks for ≥4 months) followed by pertuzumab plus trastuzumab maintenance after chemotherapy discontinuation (group B).
Results indicate that, for group A, 24-month OS was 79.0% (90% CI, 71.4%-85.4%); for group B, 78.1% (90% CI, 70.4%-84.5%). Median PFS with first-line treatment was 8.4 (95% CI, 7.9-12.0) months in group A and 23.3 (95% CI, 18.9-33.1) months in group B.
“Unlike expectations, OS and PFS did not markedly differ between populations with ERBB2-enriched and ERBB2-nonenriched cancer,” the researchers advised. “Adverse events were less common without chemotherapy, with small QOL improvements from baseline in group A and stable QOL in group B.”
Background information in the articles pointed out that MBC is considered incurable, with treatments primarily designed to control symptoms and prolong life expectancy while minimizing toxic effects and maintaining quality of life (QOL).
- Huober J, Weder P, Ribi K, et al. Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in ERBB2-Positive Metastatic Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol.Published online August 10, 2023. doi:10.1001/jamaoncol.2023.2909
