ESMO18: AstraZeneca, Merck & Co.'s PARP inhibitor Lynparza extends PFS by three years in advanced ovarian cancer

AstraZeneca and Merck & Co. on Sunday detailed results from the Phase III SOLO-1 trial at the European Society for Medical Oncology (ESMO) congress, showing that two-year maintenance therapy with Lynparza (olaparib) led to a 70-percent reduction in the risk of progression or death versus placebo in newly diagnosed patients with advanced ovarian cancer and a BRCA1 or 2 mutation. The companies reported in June that the study demonstrated a significant improvement in progression-free survival (PFS) versus placebo.

Lead study investigator Kathleen Moore said "the median PFS for patients who received placebo was only 13.8 months while the median PFS for those who received [Lynparza] was not reached, but looks to be approximately three years longer than the placebo group." Moore added that the improvement in PFS was "maintained even after [Lynparza] is stopped at two years," suggesting that the findings "herald a new era in treatment."

In the trial, 391 patients with high grade serous or endometrioid ovarian cancer who were in clinical complete or partial response after chemotherapy were randomised to receive Lynparza or placebo for two years. The study's primary endpoint was investigator-assessed PFS from randomisation, while secondary goals included PFS2, which was time from randomisation to the second progression event a patient might experience, overall survival and quality of life.

Results presented at ESMO showed that 60.4 percent of patients given Lynparza remained progression-free at 36 months, versus 26.9 percent in the placebo arm. In addition, PFS2 remained significantly improved among patients who received Lynparza with a median PFS2 of 41.9 months for placebo versus median not reached for those given the PARP inhibitor. "While it is too early to say whether we have impacted the fraction of women who could be cured with their front-line therapy, the fact that it is estimated that over 50 percent of women on the [Lynparza] arm were still progression free at four years as compared to only 11 percent for placebo speaks to this hope," Moore commented.

In the study, the most common grade 3 or higher toxicities with Lynparza were anaemia, which occurred in 22 percent of patients, and neutropaenia, which was seen in 8 percent of subjects. Meanwhile, 12 percent of patients discontinued treatment with Lynparza due to toxicity and not disease progression.

Commenting on the results for ESMO, Isabelle Ray-Coquard, from the Université Claude Bernard Lyon Est, said "not only was [Lynparza] efficacious but it was also shown to be well tolerated," adding "the findings promise to change practice in this subgroup of patients with a BRCA mutation." Ray-Coquard noted "now, two questions remain. Can we expand this benefit to all high-grade serous carcinomas?...  Also, what is the best maintenance therapy?" Ray-Coquard suggested that results from the Phase III PAOLA-1 trial, which is evaluating Lynparza with Roche's Avastin (bevacizumab) as a first-line maintenance treatment in women with newly-diagnosed advanced ovarian cancer, regardless of their BRCA status, should answer the second question when they become available in the second half of 2019.

Lynparza, which is being developed by AstraZeneca and Merck under a 2017 deal, is currently approved for the maintenance treatment of recurrent ovarian cancer in response to platinum-based chemotherapy regardless of BRCA mutation status, and for the treatment of advanced ovarian cancer patients with a germline BRCA mutation previously treated with three or more lines of chemotherapy. In January, the FDA authorised the drug for the treatment of patients with metastatic breast cancer whose disease is associated with a BRCA gene mutation, making the product the first PARP inhibitor cleared in this tumour type. Lynparza generated sales of $297 million last year, with analysts projecting that this will reach $2 billion in 2023.

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