Background: Often, when counseling patients on therapy, we utilize CT survival and toxicity data to help inform decision-making. While it is commonly believed CT data, derived from highly selected patients (pts), overestimates OS and underestimates toxicity compared with unselected patients in the RW, less is known about how often this occurs and the magnitude of this difference. We aim to quantify systematically the magnitude of OS and toxicity differences between CTs and population-based RW involving contemporary cancer systemic txs. Methods: All pts receiving IV cancer drugs with palliative intent indications that were first funded in Jan 2008 – Mar 2017 under Cancer Care Ontario’s New Drug Funding Program (NDFP) were identified. A literature search was performed to identify landmark CTs with established OS efficacy data (e.g. median OS, 1-year OS rate or Kaplan-Meier OS curves) for each drug indication. Serious adverse event (SAE) rates were collected. Drug indications were included if the public funding criteria matched the CTs’ eligibility criteria. RW OS and hospitalization (H) rates during treatment were ascertained by linking NDFP data to other population-based databases with end of follow-up at May 31, 2017. Results: 32 indications from 21 drugs (9 chemotherapy, 10 targeted therapies, 2 immunotherapy) involving 8,344 CT pts and 29,424 RW pts were included. 29 indications (91%) showed worse OS in the RW when compared to CTs with a median median OS difference of 4.4 months (IQR: 3.2-10.0) and a median 1-year OS difference of 12% (IQR: 8%-21%). Drugs used in the last-line setting had worse OS difference at 1-year (22% vs. 11%). The median difference between RW H and CT SAEs was 12% (IQR: 6%-21%). Conclusions: In most cases, substantially worse OS and greater toxicity were observed in the RW compared to CTs. This study has established a catalogue of population-based OS and H for pts receiving contemporary cancer systemic txs, and provides more relevant information for health-care providers when counseling pts on survival expectations prior to the initiation of systemic txs in the real world.