Antitumor activity
PD, SD, diarrhea
DISEASE PROGRESSION, DISEASE, BEST
In all, from September 2014 to February 2017, 24 patients finished efficacy assessment (monotherapy, Best overall response in evaluable population in monotherapy part and combination therapy part.Abbreviations: CR, complete response; DCR, disease control rate: (CR + PR + SD) %; ORR, overall response rate: (CR + PR) %; PD, progressive disease; PR, partial response; SD, stable disease.Six patients were enrolled in the 400 mg dose cohort. One patient was not evaluable. This patient received one cycle treatment and experienced Grade 3 diarrhea, which was defined as DLT. Finally, this patient dropped out of the study.This patient achieved PR after two cycles of treatment, but had PD after four cycles of treatment. So, the confirmed efficacy was SD. Cut‐off date: February 28, 2017.Waterfall plot of best objective response of all enrolled patients. Maximum reduction in target lesions from baseline for patients in the 240–480 mg dose cohorts in (A) the monotherapy part and (B) the combination therapy part. The best response for target lesions per patient was determined on the basis of RECIST 1.1 criteria. Dashed lines at −30 and 20 indicate RECIST 1.1 criteria for partial response and progressive disease, respectively. In the pyrotinib monotherapy part, the overall objective response rate (ORR) was 21% and the disease control rate (DCR) was 43%, with three patients achieving PR, three patients achieving stable disease, eight patients suffering progressive disease. The patients achieving PR were distributed in dose levels of 240, 400, and 480 mg. None of the patients achieving PR received prior anti‐HER2 regimens. The PFS ranged from 2.67 to 20.47 months. Of note, at the time of data cut‐off (February 28, 2017), one patient with PFS of 20.47 months was at the 400 mg dose level and was still ongoing with pyrotinib. Based on the safety data, PK analysis in this study and the results of phase I study in BC,In the pyrotinib combined with docetaxel part, there were two patients achieving PR, five patients experiencing SD, with the ORR and DCR of 20% and 70%, respectively. At the dose level of 400 mg, although only one patient suffered DLT, three of four patients experienced quick disease progression. Hence, the enrollment of this dose level was stopped early for poor efficacy. Based on the data of safety, PK, and efficacy, the RP2D of pyrotinib was 400 mg.