IASLC 2017: Treatment Based on BRCA1 Level Does Not Increase Survival of Stage II/III NSCLC Node-Positive Resected Patients

Key Points

  • After median follow-up of 53 months, the overall survival among the control group was 69.3 months and among the experimental group 82.3 months, ranging from 74 months (low BRCA) to 80.5 months (intermediate BRCA) and 80.2 months (high BRCA).
  • 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 (but without cisplatin) is not detrimental.
  • For patients with low BRCA1 levels, cisplatin-gemcitabine could be superior to cisplatin-docetaxel.

New research shows that treating stage II and III non–small cell lung cancer (NSCLC) node-positive resected patients with customized chemotherapy based on their specific BRCA1 expression levels, as opposed to providing the standard treatment, did not increase overall survival rates among those patients who received individualized chemotherapy. However, BRCA1 expression levels could be prognostic and treatment could achieve different outcomes. Bartomeu Massuti, MD, of Alicante University Hospital in Spain, presented findings on behalf the Spanish Lung Cancer Cooperative Group (GECP-SCLG) at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan.

For patients with resected NSCLC with lymph node involvement, postoperative platinum-based chemotherapy is the standard of care. 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. Therefore, the research team sought to determine if differential chemotherapy based on knowledge of patients’ BRCA1 levels could lead to higher survival rates and if cisplatin could be avoided in a predefined subgroup.

Study Details

The researchers hypothesized that the 5-year survival rate of the standard care control group (45%) could increase by 20% in an intervention group that received chemotherapy compatible with either their low, medium, or high BRCA1 expression levels. While those in the control group received the standard cisplatin-docetaxel, those in the experimental group either received cisplatin-gemcitabine (low BRCA1), cisplatin-docetaxel (intermediate BRCA1), or docetaxel (high BRCA1).

After median follow-up of 53 months, the overall survival among the control group was 69.3 months and among the experimental group 82.3 months, ranging from 74 months (low BRCA) to 80.5 months (intermediate BRCA) and 80.2 months (high BRCA).

Their findings suggest that survival rates do not increase among patients who receive chemotherapy based on their BRAC1 levels. 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 with docetaxel (but without cisplatin) is not detrimental. Also, for patients with low BRCA1 levels, cisplatin-gemcitabine could be superior to cisplatin-docetaxel.

“The findings from our study do not allow changing the current standard of treatment, but this trial validates BRCA1 as a prognostic factor, and selection of chemotherapy based on BRCA1 expression levels could be an option to improve outcomes, avoiding in some cases the use of cisplatin and its toxicity,” said Dr. Massuti. “Having this evidence to back up our treatment decisions is essential to providing the best care possible and also opens new opportunities for research in this setting.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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