The HER2-targeted drugs pertuzumab and trastuzumab were active in a variety of solid tumors with HER2 amplification/overexpression, but outcomes differed by KRAS status, according to results of a basket study.
The results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Funda Meric-Bernstam, MD, of MD Anderson Cancer Center in Houston.
Dr Meric-Bernstam noted that HER2 amplification or overexpression is observed in 2% to 3% of solid tumors, but HER2-directed therapies are only approved for breast, gastric, and gastroesophageal cancers.
As part of the phase 2 My Pathway study (ClinicalTrials.gov Identifier: NCT02091141), researchers wanted to determine if the combination of 2 HER2-directed therapies, pertuzumab and trastuzumab, would be effective for treating a variety of solid tumors.
Dr Meric-Bernstam reported results in 258 adult patients with HER2-amplified and/or overexpressed tumors. The patients had colorectal (n=84), biliary (n=40), non-small cell lung (n=27), uterine (n=23), urothelial (n=22), salivary (n=18), ovarian (n=12), pancreatic (n=10), and other cancers (n=22).
There were 191 patients with HER2 amplification, 30 with HER2 amplification and overexpression, 17 with amplification and mutations, 17 with overexpression, and 3 with amplification, overexpression, and mutations. (Patients who had only HER2 mutations were excluded from this analysis.)
The patients received pertuzumab (840 mg IV loading dose, then 420 mg every 3 weeks) and trastuzumab (8 mg/kg IV loading dose, then 6 mg/kg every 3 weeks) until disease progression or unacceptable toxicity.
The confirmed objective response rate (ORR) was 23.3%. There were 5 complete responses and 55 partial responses. The median duration of response was 7.9 months, and the disease control rate was 44.6%.
The median progression-free survival (PFS) was 2.8 months, and the median overall survival (OS) was 10.9 months.
Results differed by KRAS status. The confirmed ORR was 25.6% in patients with wild-type KRAS and 3.8% in patients with KRAS-mutated tumors.
The median PFS was 3.9 months in the wild-type KRAS group and 1.4 months in the KRAS-mutated group (hazard ratio [HR], 0.25; 95% CI, 0.16-0.39; P <.0001). The median OS was 12.6 months and 5.7 months, respectively (HR, 0.44; 95% CI, 0.28-0.69; P =.0002).
Evaluating outcomes by tumor type, the researchers discovered the highest ORRs in patients with salivary cancer (63.6%), pancreatic cancer (33.3%), and colorectal cancer (30.9%). The lowest ORRs were seen in patients with uterine cancer (6.3%) and ovarian cancer (10.0%).
“Our data suggest that HER2-targeted therapy may have utility in a variety of HER2-positive, KRAS wild-type tumors,” Dr Meric-Bernstam said in closing. “My Pathway also demonstrates the value of biomarker-driven basket trials for assessing efficacy across tumor types while enhancing the ability to determine the impact of co-alterations on antitumor efficacy.”
Disclosures: This research was supported by F. Hoffmann-La Roche/Genentech. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Meric-Bernstam F, Hainsworth J, Bose R, et al. MyPathway HER2 basket study: pertuzumab (P) + trastuzumab (H) treatment of a large, tissue-agnostic cohort of patients with HER2-positive advanced solid tumors. J Clin Oncol. 2021;39:(suppl 15; abstr 3004). doi:10.1200/JCO.2021.39.15_suppl.3004