Lung cancer patients lacking DNA repair protein fare better with chemotherapy

31 May 2009

An analysis from the International Adjuvant Lung Trial (IALT) reports that tumour levels of the MSH2 protein predict long-term response to cisplatin-based chemotherapy among patients with surgically removed non-small cell lung cancer (NSCLC). MSH2 is a protein that cancer cells use to repair DNA damaged by cisplatin. Researchers found that patients with no or low levels of the MSH2 protein respond better to treatment than patients with high levels.

A secondary finding of this study, being presented at the American Society of Clinical Oncology 2009 Meeting, was that the predictive value of MSH2 was equal to that of a second, previously identified protein associated with DNA repair, called ERCC1. And when tumour levels of both ERCC1 and MSH2 are taken into account, researchers report they can further identify patients most likely to benefit from cisplatin-based chemotherapy.

"We have identified new and easily performed assays that can be used to predict response to chemotherapy in patients with non-small cell lung cancer by measuring tumour levels of two key proteins – ERCC1 and MSH2," said Pierre Fouret, MD, PhD, professor at Institut Gustave Roussy (Villejuif, France) and Université Pierre et Marie Curie (Paris, France) and the study’s lead author. "This development is a step toward more personalised treatment for patients whose lung cancers have been surgically removed."

Cisplatin is commonly used as a postoperative treatment for NSCLC, but not all patients benefit. In this study, overall survival was compared between 257 patients with NSCLC whose tumors contained MSH2 ("MSH2-positive") and 416 whose tumors contained no MSH2 or low levels of this protein ("MSH2- negative"). Patients were then grouped by whether or not they underwent cisplatin-based adjuvant chemotherapy.

Adjuvant cisplatin-based chemotherapy increased overall survival among MSH2-negative patients, but did not benefit MSH2-positive patients. For MSH2-negative patients, median overall survival was 58 months for those who received cisplatin versus 42 months for those who did not receive chemotherapy. Among MSH2-positive patients, median overall survival was 49 months for those who received chemotherapy versus 58 months among those who did not.

Investigators also found that the predictive value of MSH2 and ERCC1 together was greater than either one alone. Patients with low tumor levels of both proteins who were treated with cisplatin-based chemotherapy lived 21 months longer than those who did not receive chemotherapy (55 months versus 34 months). The investigators concluded that MSH2 status may be combined with ERCC1 to predict longterm benefit from cisplatin-based chemotherapy.