Tailoring Chemo to BRCA1 Levels Did Not Improve Survival in Early Lung Cancer

Treating patients with early-stage, resected, node-positive non–small-cell lung cancer (NSCLC) with customized chemotherapy based on BRCA1 expression levels did not increase overall survival rates, according to the results of a study presented at the International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer, held October 15–18 in Yokohama, Japan.

However, according to results presented by Bartomeu Massuti, MD, of Alicante University Hospital in Spain, BRCA1 expression levels could be prognostic and treatment could achieve different outcomes.

BRCA1 is a DNA repair factor that is mainly involved in the repair of double strand DNA breaks and may also act as a differential regulator of response to cisplatin and antimicrotubule agents. BRCA1 efficiency enhances resistance to cisplatin, and loss of BRCA1 function is associated with sensitivity to DNA-damaging chemotherapy.

Based on this knowledge Massuti and colleagues designed a study to test if differential chemotherapy treatment based on BRCA1 expression levels led to higher survival rates, and if cisplatin could be avoided in certain subgroups.

The study included 500 patients who were randomly assigned to a control group or an experimental group with different chemotherapy regimens according to BRCA1 expression levels (n = 392). Patients in the control group received standard cisplatin/docetaxel. Patients in the experimental group received cisplatin/gemcitabine (low BRCA1 expression), cisplatin/docetaxel (intermediate expression), or docetaxel alone (high expression).

Overall survival between the two study arms was not significantly different. After a median follow-up of 53 months, the overall survival of the control group was 69.3 months and it was 82.3 months in the experimental group. Within the experimental arm, survival ranged from 74 months for those with low BRCA1 to 80.5 months for intermediate expression to 80.2 months for those with high expression.

However, the researchers did find higher rates of survival than expected in patients with lymph node involvement, and also determined that in the case of high levels of BRCA1, chemotherapy treatment with docetaxel alone was not detrimental.

“We have validated the prognostic value of BRCA1 expression levels in these early-stage NSCLC patients,” Massuti said. “We have found that in the subgroup with low BRCA1 levels, one combination of cisplatin/gemcitabine was superior to the other combinations, and for the subgroup with high BRCA1 levels cisplatin could be avoided.”