Ado-trastuzumab Emtansine Effective in HER2 Amplified Non-breast, Non-gastric Cancers
Ado-trastuzumab emtansine may have anticancer activity in HER2-amplified cancers.
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Significant overall response rates (ORRs) were achieved with ado-trastuzumab emtansine for several non-breast, non-gastric cancers with HER2 amplification, according to an oral presentation at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.
HER2 amplication occurs in 2% to 5% of non-breast, non-gastric cancers. Ado-trastuzumab emtansine, a HER2 targeted antibody drug conjugate, may have anticancer activity in HER2-amplified cancers. Therefore, researchers at Memorial Sloan Kettering Cancer Center, in New York, New York, sought to determine the efficacy of ado-trastuzumab in this patient population.
For the multihistology basket trial (ClinicalTrial.gov Identifier: NCT02675829), researchers enrolled 58 patients with HER2 amplified lung, endometrial, salivary gland, biliary tract, ovarian, bladder, colorectal, or other cancers; median age was 63 (range, 34 to 90 years); 72% were female. Participants had received 1 to 7 prior systemic therapies. HER2 amplification was identified by next-generation sequencing (NGS). Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) testing was subsequently obtained for tumors with adequate tissue samples.
Patients received ado-trastuzumab emtansine 3.6 mg/kg IV every 3 weeks. Primary end point was ORR using RECIST v1.1 or PERCIST. Applying a Simon 2-stage optimal design to each histology cohort, type 1 error rate was under 2.7%, power of 89%, H0 10%, H1 40%. In addition, researchers measured duration of response (DOR), progression-free survival (PFS), and toxicity.
Results showed an overall response rate of 26% (14/53 confirmed; 95% CI 15-40%). Among patients with lung cancer, response rate was 50% (3/6); among those with endometrial cancer, 22% (4/18, 2 complete response [CR]); among those with salivary cancers, 100% (5/5, 3 CR); among those with biliary cancer, 17% (1/6); and among those with ovarian cancer, 17% (1/6), not including partial responses awaiting confirmation.
Secondary end points included median DOR 6 months (range, 2 to 22+) and median PFS 3 months (95% CI 2-6). One (2%) case of grade 3 febrile neutropenia was reported, but no treatment-related deaths were reported.
Response was not predicted by degree of HER2 amplification (NGS fold change 1.7 to 27.9). HER2 amplification by NGS correlated well with HER2/CEP17≥2 by FISH (40/41 tested) or IHC3+ (31/40 tested). Tumor shrinkage was seen in 2 patients who were tested IHC negative.
The researchers concluded that “ado-trastuzumab emtansine showed efficacy in patients with HER2 amplified lung, endometrial, salivary gland, biliary tract, and ovarian cancers as identified by NGS.”
Li BT, Makker V, Buonocore DJ, et al. A multi-histology basket trial of ado-trastuzumab emtansine in patients with HER2 amplified cancers. Oral presentation at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.