Anti-HER2 Drugs May Benefit Some Lung Cancer Patients

An analysis of data on non–small cell lung cancer (NSCLC) patients with HER2 mutations has raised hopes that anti-HER2 drugs used to treat HER2-positive breast cancer might also benefit a small percentage of lung cancer patients.

In a retrospective study published in the Journal of Clinical Oncology, Julien Mazières, MD, PhD, a professor at Hôpital Larrey in Toulouse, France, and his colleagues combed through the records of 3,800 NSCLC patients from France, Switzerland, and Spain and identified 65 (1.7%) as having HER2 mutations that appear to be drivers for their adenocarcinomas. These patients had a median age of 60 years, and 45 of them were female. About half had never smoked.

Among the 65 patients, 22 who had stage IV cancer at diagnosis were treated with the anti-HER2 drugs trastuzumab (Herceptin; Genentech) or afatinib (Tomtovok; Boehringer Ingelheim) after receiving conventional chemotherapy. Eighteen of them (82%) experienced a partial response or stabilization of their disease.

Mazières says he is designing a clinical trial that would test the effectiveness of anti-HER2 drugs in patients with HER2-mutated NSCLC but cautioned against over-interpreting the results of his retrospective study: “I think this is just the beginning of the story of HER2 in lung cancer.”

“There are more and more molecular subtypes of lung cancer being identified, and we ought not to ignore this one,” comments Pasi Jänne, MD, PhD, an associate professor at Harvard Medical School and Dana-Farber Cancer Institute in Boston, MA, who was not involved in the study.

Jänne says these results and others justify testing for HER2 mutations and referring patients for possible enrollment in one of several ongoing clinical trials of anti-HER2 drugs. However, tests for genetic abnormalities in the EGFR and ALK genes should take priority, he says, because therapies have been approved for lung cancers associated with those genetic defects.

HER2 had previously been implicated in the development of some cases of NSCLC, but interest in anti-HER2 drugs for the disease fizzled after disappointing results for trastuzumab were reported, according to Mazières.

Mazières says his retrospective study yielded evidence of anti-HER2 drug effectiveness by looking at tumors harboring a HER2 mutation—an insertion in exon 20—separately rather than lumping them in with NSCLC tumors with HER2 amplification or overexpression. “I think the key molecular event is the mutation,” he says. “Amplification is a different story.”