Low expression of MSH2 protein predicts survival in NSCLC

Low tumor levels of the MSH2 protein predict long-term response to cisplatin-based chemotherapy in patients with resected non-small-cell lung cancer, according to an analysis from the International Adjuvant Lung Trial.

The human MutS homolog 2 (MSH2) protein is required to repair DNA damage exerted by cisplatin. An earlier analysis of IALT, which showed the benefit of adjuvant chemotherapy in 1,865 early-stage NSCLC patients, found that low levels of ERCC1, another DNA repair protein, were also predictive of a treatment benefit (Clin Cancer Res 13:3892-3898, 2007 and 11:5017s-5021s, 2005; J Clin Oncol 25:2735-2740, 2007).

In the current study, overall survival (OS) was compared between 257 patients whose tumors expressed MSH2 (38%) and 416 whose tumors contained no MSH2 or low levels of this protein (68%). Adjuvant cisplatin-based chemotherapy was associated with improved survival among MSH2-negative patients but did not benefit MSH2-positive patients, reported Pierre Fouret, MD, PhD, professor at the Institut Gustave Roussy, Villejuif, France, and the Universit Pierre et Marie Curie in Paris (ASCO 2009 abstract CRA7502).

Median survival was 58 months for MSH2-negative patients who received chemotherapy, compared with 42 months for patients randomized to no chemotherapy. For MSH2-positive patients, median OS was 49 months with chemotherapy and 58 months without.

“There was an overall survival gain of 16 months from chemotherapy in patients with low MSH2,” Dr. Fouret said.

In an evaluation of the subset of 658 patients for whom both biomarkers were available, median follow-up at 7.5 years showed the two proteins to have equal predictive power.

When MSH2 and ERCC1 were used together, the predictive value was greater than for either alone. Patients with low tumor levels of both proteins who were treated with cisplatin-based chemotherapy lived 21 months longer than those not receiving chemotherapy (55 months vs 34 months). In this group, mortality risk was reduced by 35% (P = .01).

“The long-term survival benefit from cisplatin-based chemotherapy may be different according to MSH2 expression, and there is better prediction of chemotherapy benefit when both biomarkers are used together,” Dr. Fouret said.