Ado-trastuzumab Emtansine Effective in HER2 Amplified Non-breast, Non-gastric Cancers

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Ado-trastuzumab emtansine may have anticancer activity in HER2-amplified cancers.
Ado-trastuzumab emtansine may have anticancer activity in HER2-amplified cancers.
The following article features coverage from the American Society of Clinical Oncology (ASCO) 2018 meeting. Click here to read more of Oncology Nurse Advisor's conference coverage.

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.”

Reference

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.

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