Lynparza boosts gastric cancer overall survival19 Aug 2015
A new phase 2 study revealed that the combination of olaparib (Lynparza) and paclitaxel was active in patients with metastatic gastric cancer. Furthermore, it was proved that the overall survival (OS) beneﬁt was relative to paclitaxel alone in patients with low or undetectable levels of a DNA damage response gene known as ATM.
According to Yung-Jue Bang, MD, PhD, and colleagues, Olaparib/paclitaxel significantly improved overall survival versus placebo/paclitaxel in the overall study population. Moreover, he added that the combination also significantly improved OS versus placebo in the ATMlow patients.
Clinical trial conducted in Korea
These findings came from a phase 2, double-blind study; a phase 3 trial in this setting is currently underway. In the study, 266 patients were enrolled at 13 sites in Korea from February 2010 to May 2012. Approximately 90% of patients had previously received platinum plus ﬂuoropyrimidine.
The study population was enriched to 50% for patients with ATMlow. Demographics and baseline characteristics were balanced between the two treatment groups, said the investigators.
Well tolerated adverse events
The combination was generally well tolerated, with no unexpected safety findings, said Bang. Neutropenia, the most common adverse event in both study arms, contributed to more dose modiﬁcations in the olaparib/paclitaxel arm than in the placebo/paclitaxel arm. This, in turn, led a lower median dose-intensity of paclitaxel in the olaparib/paclitaxel arm.
The higher incidence of neutropenia in the olaparib/paclitaxel arm was apparent by the 1st treatment cycle and remained higher throughout the course of treatment. However, few patients experienced febrile neutropenia or neutropenia of more than two weeks' duration, said Bang.
Difficulty to evaluate the response and disease progression
Surprisingly, given that so many oncology drug studies find improvements in progression-free survival (PFS) but not overall survival, there was no significant PFS benefit in the current trial, in either the overall population; or in the ATMlow population
Addressing the lack of PFS benefit, Barbara Burtness, MD, of Yale University School of Medicine noted that the study included a substantial proportion of patients with peritoneal metastases, "which is notably more difficult to evaluate for response or progression than other metastatic sites and possibly associated with inferior outcome.”
Other limitations of the trial, according to Burtness, included small sample size, poorly defined duration of chemotherapy and a "hypothesis of a hazard ratio of 0.55 in the ATM-enriched population [that] was ambitious."Still, biomarker-enriched study of novel targeted therapies is a complex undertaking, she suggested.Source: MedPage Today