HER2-positive non-small cell lung cancer responds with targeted drugs

HER2-positive non-small cell lung cancer responds with targeted drugs

29 Sep 2014

Patients who have non-small cell lung cancer with HER2 mutations may have treatment options from targeted drugs, according to data from a phase 2 randomized trial of neratinib and temsirolimus presented at the ESMO 2014 Oncology congress in Madrid.

CareAcross-DNA-strands

1-2% of non-small cell lung cancers are HER2 mutated

“HER2 mutated non-small cell lung cancer patients are a small subset of non-small cell lung cancer patients—around 1-2%—but it seems important to inhibit HER2 for these patients,” says lead author Dr Benjamin Besse, head of the thoracic cancer unit at Gustave Roussy, Paris, France.

On a more scientific note, neratinib inhibits the HER2 receptor while temsirolimus inhibits mTOR, a protein that belongs to the signaling cascade of HER2, Besse says.

Phase 2 trial: 27 patients with metastatic disease

In a randomized, two-stage study, 27 patients with advanced, metastatic non-small cell lung cancer whose tumors tested positive for HER2 somatic mutations were randomized either to treatment with oral neratinib alone (240 mg od continuously), or in combination with intravenous temsirolimus (8 mg/week, dose escalation to 15 mg/week after one three-week cycle if tolerated, at the investigator’s discretion).

Preliminary results: 21% overall response rate, manageable side effects

Preliminary results from stage one of the ongoing study show the combination of neratinib and temsirolimus has a 21% overall response rate in 14 patients, with a median progression-free survival of 4 months.

Researchers did observe more gastrointestinal effects such as diarrhea from combination therapy compared to neratinib alone, but it was not a limiting toxicity and the side effect was managed up front with prophylactic loperamide.

Comments from principal investigator and others

In summary, Besse says, “HER2 mutated non-small cell lung cancer represents a very small number of patients, but it reflects the new face of NSCLC – it is not a single homogeneous disease, but a lot of different molecularly defined subsets of patients with potential ‘drugable targets’, for which specific strategies should be addressed.”

Commenting on the two studies, Dr Fiona Blackhall, medical oncologist and senior lecturer at The Christie NHS Foundation Trust, and Manchester University, Manchester, United Kingdom, says the results reinforce that diagnosis of the molecular subtype of lung cancer is central to identification of more effective treatments. “Studies of targeted approaches in molecularly defined subsets of non-small cell lung cancer are consistently yielding better response rates and survivals than historical studies conducted in non molecularly selected populations,” Blackhall says. “The principles of precision medicine are proven for non-small cell lung cancer, and now efforts must intensify to ensure equitable access to molecular diagnostics for patients with this disease.”

 

Source: eCancer News

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