e18228 Background: Oncology drug development has shifted away from cytotoxic agents, while they remain widely used in clinical practice. We sought to estimate the proportion of U.S. patients with advanced or metastatic cancer who are eligible for and may respond to standard first-line cytotoxic chemotherapy alone based on National Comprehensive Cancer Network (NCCN) treatment guidelines. Methods: This retrospective review used publicly available annual mortality data from the American Cancer Society to estimate the number of patients who would have presented with advanced or metastatic disease. Published clinical trials of first-line cytotoxic-only regimens as advised by the NCCN were used to calculate overall response rates (complete plus partial response) for each cancer type. Chemotherapies in combination with immunotherapy or biologic agents were excluded. Mean response rate was used when there was more than one recommended regimen. The main outcome was to identify the proportion of patients with advanced or metastatic cancer who are eligible for and may respond to standard first-line cytotoxic chemotherapy regimens based on cancer type. Results: We identified 92 different cytotoxic chemotherapy regimens used in 25 cancer types. Among an estimated 609,640 cancer-related deaths in 2018, 479,823 (78.7%) would be eligible to receive standard first-line cytotoxic chemotherapy. We estimated 189,159 of 609,640 (31.0%) patients to achieve at least partial response. The median objective response rate was 48.6% (range 9.2%-90.6%). The following cancers had the highest response rate to cytotoxic chemotherapy: acute lymphoblastic leukemia (90.6%), acute myeloid leukemia (76.7%), and uterine cancer (75%). The following had the greatest number of patients who may respond to cytotoxic chemotherapy: lung cancer (60,234 of 609,640; 9.9%), colorectal cancer (23,138; 3.8%), and non-Hodgkin lymphoma (14,773; 2.4%). Conclusions: Given the large proportion of patients who may benefit from cytotoxic agents, drug development in this space may warrant continued interest in specific cancer types. Also, the regulatory approval of novel oncology drugs may justify head-to-head comparison against modern chemotherapy regimens.