AbstractIntroductionCancer patients are frail individuals, thus the prevention of SARS‐CoV‐2 infection is essential. To date, vaccination is the most effective tool to prevent COVID‐19. In a previous study, we evaluated the immunogenicity of two doses of mRNA‐based vaccines (BNT162b2 or mRNA‐1273) in solid cancer patients. We found that seroconversion rate in cancer patients without a previous exposure to SARS‐CoV‐2 was lower than in healthy controls (66.7% vs. 95%,p= 0.0020). The present study aimed to evaluate the clinical efficacy of the vaccination in the same population.MethodsThis is a single‐institution, prospective observational study. Data were collected through a predefined questionnaire through phone call in the period between the second and third vaccine dose. The primary objective was to describe the clinical efficacy of the vaccination, defined as the percentage of vaccinated subjects who did not develop symptomatic COVID‐19 within 6 months after the second dose. The secondary objective was to describe the clinical features of patients who developed COVID‐19.ResultsFrom January to June 2021, 195 cancer patients were enrolled. Considering that 7 (3.59%) patients tested positive for SARS‐CoV‐2 and 5 developed symptomatic disease, the clinical efficacy of the vaccination was 97.4%. COVID‐19 disease in most patients was mild and managed at home; only one hospitalization was recorded and no patient required hospitalization in the intensive care unit.DiscussionOur study suggests that increasing vaccination coverage, including booster doses, could improve the prevention of infection, hospitalization, serious illness, and death in the frail population of cancer patients.