Primary Objective: • To compare the efficacy of DS-8201a to investigator’s choice by means of progression-free survival (PFS). Secondary Objectives: • To further investigate the efficacy of DS-8201a compared to investigator’s choice on: ? Overall survival (OS); ? Objective response rate (ORR); ? Duration of response (DoR); ? Clinical benefit rate (CBR). • To further determine pharmacokinetics (PK) of DS-8201a. • To further evaluate safety of DS-8201a compared to investigator’s choice. • To evaluate Health Economics and OutcomesResearch (HEOR) endpoints for DS-8201a compared to investigator’s choice. Exploratory Objectives: • To evaluate potential biomarkers (eg, serum HER2-extracellular domain [HER2ECD]). • To evaluate exposure-response relationships for efficacy and safety endpoints.