OBJECTIVES: The European Medicines Agency (EMA) approved 19 oncologics across 25 indications on the basis of pivotal Phase II data lacking an active comparator (Macaulay, ISPOR Dublin 2013). Approval was typically granted for indications in which there was no therapeutic alternative where a response rate of ≥35% was demonstrated. This research aims to define the circumstances under which the Food and Drug Administration (FDA) will approve oncologics on the basis of pivotal Phase II data and compare to those of the EMA. METHODS: A systematic search was undertaken for FDA oncologic submissions based on pivotal Phase II data and the acceptance decision, indication, and level of benefit were extracted. RESULTS: CONCLUSIONS: Pivotal Phase II data can support FDA oncologic approvals for indications that lack therapeutic alternatives and demonstrate response rates of ≥10% (versus ≥35% for the EMA). The lower threshold enables more drugs for severe diseases to become available earlier in their development cycle but risks approving ineffective and/or unsafe drugs.