*2.3. Statistical Methods*

The ORR was calculated as the proportion of subjects with complete response or partial response as their best treatment responses. The DCR was calculated as the proportion of subjects who achieved stable disease (or better) as their best treatment response. The PFS interval was calculated from the date of enrollment to the first instance of disease progression, death from any cause, or the last follow-up without evidence of progression (for surviving patients with no evidence of progression). The OS interval was calculated from the date of enrollment to the date of death from any cause. Adverse events were evaluated from the first drug administration to 30 days after the last drug administration and were graded based on the Japanese JCOG translation of version 4.0 of the Common Terminology Criteria for Adverse Events.

The Wilson method was used to estimate the ORR and DCR with their two-sided 95% CIs. Statistical significance was considered present when the lower limit of the estimated 95% CI was above the threshold of 35% for ORR. The Kaplan–Meier method was used to evaluate the survival curves for PFS and OS, as well as the median and annual values. The Brookmeyer and Crowley method was used to estimate the CI values for median values, and Greenwood's formula was used to estimate the standard error for annual values.
