AT ASCO 2017
CHICAGO (FRONTLINE MEDICAL NEWS) –Beyond its role in advanced breast cancer, the antibody-drug conjugate ado-trastuzumab-emtansine (T-DM1; Kadcyla) showed modest activity in some patients with metastatic non–small cell lung cancer (mNSCLC) overexpressing the human epidermal growth factor-2 (HER2) receptor, investigators reported.
In an ongoing phase II study, 4 of 20 patients with mNSCLC whose tumors expressed the highest levels of HER2 had partial responses. In contrast, none of the 20 patients with tumors overexpressing HER2 at lower levels had responses, reported Thomas E. Stinchcombe, MD, of Duke University, Durham, N.C.
“Additional investigation into improved detection of HER2 amplification and other biomarkers may help to refine the patient population that is likely to benefit from T-DM1,” he said at the annual meeting of the American Society of Clinical Oncology.
Previous studies have shown that HER2 overexpression by immunohistochemistry (IHC) is associated with poor prognosis in patients with NSCLC, but in contrast to breast and gastric cancers, HER2 overexpression in NSCLC is not always accompanied by HER2 amplifications.
“HER2 amplifications and HER2 mutations are generally mutually exclusive in NSCLC. Given the known mechanism of action of T-DM1, HER2 overexpression was chosen as an inclusion criterion for this study,” Dr. Stinchcombe said.
They enrolled patients with HER2-overexpressing mNSCLC who had disease progression following platinum-based chemotherapy. The patients were assigned to one of two 20-patient cohorts based on IHC2+ (10% or more of cells stained with 2+ intensity), or IHC3+ (10% or more of cells stained with 3+intensity).
For the primary endpoint of treatment response none of the patients in the IHC2+ cohort had objective responses by Response Evaluation Criteria in Solid Tumors (RECIST), although eight patients in this cohort had stable disease, including one patient who remained in stable disease status on treatment out to 21 months at last follow-up.
In the IHC3+ cohort, four patients had partial responses, for an objective response rate of 20%. The median duration of response was 7.3 months. Two patients in this cohort had stable disease.
Median PFS was similar between the cohorts, at 2.6 months for IHC2+ and 2.7 months for IHC3+. The respective median OS durations were 12.2 and 12.1 months.
The safety profile of T-DM1 in this population was similar to that seen in breast cancer. There were two grade 3 serious adverse events: one infusion-related hypersensitivity reaction, and one case of thrombocytopenia. There were 10 grade 3 events of any kind, 1 grade 4 event, and 1 treatment withdrawal due to a grade 2 infusion reaction.
The unremarkable findings from this study raise the question of whether HER2 is the right target in this population, said Leena Gandhi, MD, PhD, of New York University Langone School of Medicine in Manhattan, the invited discussant.
“I think it’s honestly a little hard to tell from this study, which is very small, whether there is really a role of [HER2] overexpression in actually driving oncogenesis and being a target for T-DM1,” she said.
Dr. Stinchcombe reported institutional research funding from Hoffmann-LaRoche, which sponsored the trial, and several coauthors are employees of the company.