Discussion
non-small cell lung cancer, ovarian cancer, nausea, neutropenia, toxicity, Nausea, high-grade serous ovarian carcinoma
NON-SMALL CELL LUNG CANCER, OVARIAN CANCER, NEUTROPENIA, ADVERSE EVENTS, SOLID TUMORS, ADVERSE EVENT, DISEASE CHARACTERISTIC
In the subgroup analysis presented here, Japanese patients with high-grade serous ovarian carcinoma who received veliparib combined with platinum-based chemotherapy and continued as maintenance experienced numerically longer progression-free survival compared with Japanese patients who received platinum-based chemotherapy alone. This was consistent with the previously published primary analysis of this trial [As gThe most common adverse events observed in Japanese and non-Japanese patients in the veliparib-throughout arm were nausea (100% and 79%, respectively) and neutropenia (100% and 74%), and these adverse events occurred at greater frequencies than in the respective control arms (nausea: 74% and 67%, neutropenia: 91% and 66%). The toxicity profile observed in the veliparib-throughout arm for the Japanese subgroup is comparable with that observed in small phase 1 studies of veliparib as a single agent or combined with carboplatin/paclitaxel in patients with ovarian cancer or other solid tumors [Although pharmacokinetic drug profiles are known to differ among patients of different ethnicities [With the comparable veliparib pharmacokinetic profiles in Japanese and non-Japanese patients, the reason for observed differences in frequency of some adverse events between the populations is unclear. Different polymorphisms between populations may lead to differential sensitivity to drug. In a previously reported study, it was hypothesized that the differences in allelic distribution in genes involved in paclitaxel metabolism or DNA repair between Japanese and Western populations may result in differential sensitivity to paclitaxel. However, no significant associations were identified between adverse event frequency and the polymorphisms explored [The present study assesses the efficacy and safety of PARP inhibitor therapy during combination chemotherapy and continued as maintenance in patients with newly diagnosed ovarian cancer. Other studies in newly diagnosed patients have generally evaluated PARP inhibitors as maintenance therapy after combination chemotherapy only [Although the analysis of progression-free survival in Japan subgroup was prespecified, it was not powered for statistical significance and is limited by the relatively small number of patients. While baseline demographic and disease characteristics were generally balanced between treatment arms within the larger non-Japanese subgroup, there were some imbalances within the Japanese subgroup.Conclusions drawn on differences in rates of specific adverse event rates between Japanese and non-Japanese subgroups are limited by the relatively small number of patients in the Japanese subgroup. Despite the small numbers in the Japanese subgroup, there are consistencies between the observations in this study and in other previous reports. For example, the higher rate of neutropenia observed in the Japanese subgroup vs the non-Japanese subgroup is consistent with a previous report indicating higher rates of grade 3/4 neutropenia for Japanese vs American patients with non-small cell lung cancer receiving carboplatin and paclitaxel [Although nausea was common, it was predominantly low-grade. Nausea was also reported less frequently during the maintenance phase than the combination phase in both Japanese (maintenance: 