Most Read Articles
Dr. Alexander Drilon, 19 Jul 2017
With the dramatic evolution of sequencing technology and emergence of effective targeted therapies, using a comprehensive molecular approach to guide treatment decisions is becoming more accessible and applicable in the clinic. At the recent Foundation Medicine meeting in Hong Kong, Dr Alexander Drilon, clinical director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center (MSKCC), New York, US, discussed the current landscape and potential benefits of comprehensive molecular profiling in non-small cell lung cancer (NSCLC).

Rucaparib boosts PFS in BRCA-mutant recurrent ovarian cancer

Elaine Tan
21 Sep 2017

Rucaparib maintenance therapy increases progression-free survival (PFS) in BRCA-mutant recurrent ovarian cancer (OC) by 77 percent, according to late-breaking results from the ARIEL3 trial presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain.

The trial investigated PFS in 564 patients with high-grade recurrent OC (disease progression ≥6 months after penultimate platinum) who had achieved either a complete response (according to RECIST v1.1) or partial response (RECIST v1.1 or Gynecologic Cancer InterGroup CA-125 criteria) to their last platinum-based therapy. The patients were randomized in a 2:1 ratio to receive rucaparib 600 mg BID maintenance therapy or placebo. [ESMO 2017, abstract LBA40_PR]

Investigators assessed the PFS benefit of rucaparib (a PARP inhibitor with antitumour activity in BRCA-mutant OC or BRCA wild-type OC with high genomic loss of heterozygosity [LOH]) vs placebo sequentially in three groups: group 1 comprising patients with BRCA mutations (deleterious germline or somatic BRCA mutation), group 2 comprising patients with homologous recombination deficient (HRD) OC (BRCA-mutant or BRCA wild-type with high LOH), and group 3 comprising the entire intent-to-treat population.

“Results showed that compared with placebo, rucaparib led to a significant improvement in median PFS in all three groups, with the greatest improvement seen in group 1 [5.4 vs 16.6, 13.6 and 10.8 months, respectively; p<0.0001; hazard ratios, 0.23, 0.32, and 0.36, respectively],” reported lead author Professor Jonathan Ledermann of UCL Cancer Institute, London, UK.

Exploratory analyses in non-nested subgroups of patients with BRCA wild-type OC found that rucaparib treatment significantly improved PFS vs placebo. “However, as expected, a greater magnitude of PFS benefit was seen in those with high LOH [median PFS, 11.1 vs 5.6 months with placebo; p=0.0135] than those with low LOH [median PFS, 8.2 vs 5.3 months; p=0.0003],” said Ledermann.

“PFS benefit with rucaparib treatment was not dependent on time to progression since penultimate platinum therapy or whether patients had partial or complete response to their last platinum therapy,” he highlighted.

In ARIEL3, rucaparib was well tolerated with a safety profile consistent with previous phase II studies. The most common grade 3 treatment-emergent adverse events (TEAEs) associated with rucaparib were anaemia (18.8 percent vs 0.5 percent with placebo) and increase in alanine/aspartate aminotransferase levels (10.5 vs 0 percent).  “However, elevations were transient, self-limiting and not associated with other signs of liver toxicity,” Ledermann noted.

At the visit cut-off date (15 Apr 2017), 13.4 percent of patients in the rucaparib group vs 1.6 percent in the placebo group discontinued treatment due to TEAEs (excluding disease progression), and 1.6 vs 1.1 percent died due to adverse events (including disease progression).

“PARP inhibitors are the biggest development in OC therapy since the introduction of platinum drugs in the late 1970s and early 1980s. Rucaparib is clearly an exemplary member of this exciting class of drugs that can be used to treat women with recurrent OC in the maintenance setting,” Ledermann concluded.

Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Oncology - Malaysia digital copy today!
DOWNLOAD
Editor's Recommendations
Most Read Articles
Dr. Alexander Drilon, 19 Jul 2017
With the dramatic evolution of sequencing technology and emergence of effective targeted therapies, using a comprehensive molecular approach to guide treatment decisions is becoming more accessible and applicable in the clinic. At the recent Foundation Medicine meeting in Hong Kong, Dr Alexander Drilon, clinical director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center (MSKCC), New York, US, discussed the current landscape and potential benefits of comprehensive molecular profiling in non-small cell lung cancer (NSCLC).