PARP Inhibitor Treatment Shows Promise for Patients with Small Cell Lung Cancer

The addition of the poly ADP-ribose polymerase (PARP) inhibitor veliparib to a standard chemotherapy agent improved overall response rates (ORR) in patients with small cell lung cancer (SCLC), according to recent data from a phase 2 clinical trial. Researchers also identified a biomarker that may indicate which patients will benefit most from the treatment.

The phase 2 study, led by researchers at The University of Texas MD Anderson Cancer Center, evaluated 104 patients with relapsed SCLC from 7 centers across the country between 2010 and 2015.

In addition to an improved ORR, the researchers also found that patients whose tumors expressed SLFN11 saw a progression-free survival (PFS) and overall survival (OS) benefit, suggesting a promising biomarker for PARP-inhibitor sensitivity in SCLC. This is the first study to investigate SLFN11 as a predictive biomarker in a clinical setting.

Despite recent advancements in immunotherapy for non-small cell lung cancer, patients with SCLC have not received as many promising advances for treatment.

“Currently the survival for most small cell lung cancer patients is less than a year—it’s the sixth leading cause of cancer death in the US, independent of non-small cell lung cancer,” Lauren Averett Byers, MD, associate professor of Thoracic/Head and Neck Medical Oncology, study author, said in a press release. “We currently have no approved targeted therapies, no biomarkers. Patients desperately need new treatment options. However, I think we are on the cusp of changing the outlook for our patients.”

PARP inhibitors, which are currently approved for the treatment of BRCA-mutated metastatic breast cancers and ovarian cancers, work by blocking a DNA repair pathway.

In the study, patients were randomized to receive either veliparib or placebo twice daily, with a standard chemotherapy regimen temozolomide (TMZ). Many of the patients had advanced disease with brain metastasis and/or had failed standard chemotherapy.

Patients in the unselected population did not reach a statistically significant difference in PFS between the TMZ/veliparib cohort and the TMZ/placebo cohort at 4 months. In both groups, the median OS was similar at 8.2 months and 7 months, respectively.

However, the ORR was almost 3 times higher in the TMZ/veliparib cohort (39%) compared with the TMZ/placebo cohort (14%). The ORR was defined as the percentage of patients with tumor shrinkage.

The researchers also found that in patients whose tumors expressed elevated levels of SLFN11, treatment with TMZ/velaparib resulted in significantly prolonged PFS, 5.7 versus 3.6 months, and OS, 12.2 months versus 7.5 months.

“Currently, there are no biomarkers for the management of this disease. To be able to select patients for the appropriate treatment would significantly change the care we are able to offer,” Dr Byers said in the press release.

The findings represent a step toward developing the first targeted therapy to benefit patients with SCLC, potentially leading to more treatment options for this patient population.

Reference

PARP inhibitor improves overall response rates in small cell lung cancer patients [news release]. MD Anderson’s website. https://www.mdanderson.org/newsroom/2018/06/parp-inhibitor-improves-overall-response-rates-in-small-cell-lung-cancer-patients.html. Accessed June 12, 2018.