Background: The efficacy of SARS-COV-2 vaccination has been demonstrated in healthy individuals. Immune responses are less well characterised in cancer patient groups, especially those receiving anticancer therapy (e.g. immune therapy, chemotherapy and targeted therapies. We aim to assess the immune response to the SARS-COV-2 vaccination in patients with solid organ cancer on different systemic anti-cancer therapies. Methods: All patients received 2 doses of COVID-19 mRNA vaccination as part of the UK National vaccination programme; with the second booster dose administered within 12 weeks of the first dose. All patients received either BNT162b2 (Pfizer/BioNTech) or ChAdOx1 S (AstraZeneca) vaccines. Sequential serum samples were collected pre-booster dose vaccination (baseline/within -30 days) and after second dose SARS-COV-2 vaccination, at 14-35 days and 36-63 days. Presence and titres of serum Anti-SARS-CoV-2 Spike protein (S) antibody titres were measured. Seroconversion is defined as a response ≥0.8 U/ml, and maximum response to Anti-S is defined as ≥250 U/ml. Responses were measured in 3 patient groups according to the type of anti-cancer therapy: chemotherapy (CHT group), immune therapy (IO group) and targeted therapies, mainly VEGF TKI (TT group). Results: Overall, 61 patients were recruited: 45.9%(28/61) in CHT group, 32.8% (20/61) in IO group and 21.3% (13/61) in the TT group. Baseline characteristics were comparable between patient groups. In response to the booster dose vaccination at 14-35 days, the number of patients who seroconverted was 79.3% (23/29), 94.7% (18/19) and 84.6% (11/13) in the CHT, IO and TT groups, respectively. At this same time point, 51.7% (15/29) in the CHT group achieved maximum anti-S titre levels (≥250 U/ml), compared with 78.9% (15/19) of patients in IO group and 69.2% (9/13) of patients in TT group. All 3 groups demonstrated a significant increase in Anti-S antibodies at 14-35 days after second dose vaccine when compared to pre-booster serum levels, with the largest increase seen in the IO group with a mean Anti-S increase of 149.1 U/ml (SD±105.0, p < 0.0001) followed by the TT group mean increase 120.2 U/ml (SD ±110.8, p < 0.01) and the CHT group, mean increase 83.0 U/ml (SD ±108.4, p < 0.001). Anti-S antibody levels were sustained at 36-63 days post-booster across all groups. However only IO patients had a sustained immune response to vaccination, with median Anti-S titres level of ≥250 U/ml and a significant drop was seen in the CHT group (median Anti-S level 138, p < 0.05). Conclusions: Anti-S titres increase following vaccination in all 3 groups but remain most sustained in the IO group at 36-63 days post-vaccination. Chemotherapy and other targeted therapy treated patients may benefit from early COVID-19 vaccine boosters, compared to patients receiving immune therapy.