Robust data proves vaccination against COVID-19 is effective in patients with cancer
Third, booster dose may improve immune response in patients with cancer with no sufficient protection after second dose
Large body of research concordantly demonstrates safety of vaccines in this population
Lugano, Switzerland, 20 September 2021 – The long-awaited confirmation of the efficacy of COVID-19 vaccination in patients with cancer has arrived, on time to be disseminated to a global audience at the annual congress of the European Society for Medical Oncology (ESMO Congress 2021), the leading professional society for medical oncology. With a multitude of studies supporting similar conclusions still to be presented (tomorrow), new research revealed today that individuals with cancer have an appropriate, protective immune response to vaccination without experiencing any more side-effects than the general population. Indirect evidence suggests that a third “booster” shot could further increase the level of protection among this patient population.
As patients with cancer were excluded from the clinical trials conducted to develop the vaccines and support their authorisation for use, the questions of whether the vaccines are safe in this vulnerable population and whether they provide adequate protection against severe forms of COVID-19 to individuals whose immune system may be weakened by various anticancer medicines had until now been left open.
“The ESMO annual congress, held for the second time in a virtual format this year in an extra effort to protect our colleagues, has devoted significant efforts to making COVID-19 a priority,” said ESMO Chief Medical Officer George Pentheroudakis. “The fact that we have received more than 90 abstracts on the topic, with excellent data, is a clear demonstration that this was the right thing to do.”
Patients with cancer protected regardless of current oncology treatment
To explore the potential impact of chemotherapy and immunotherapy on the protection afforded by vaccination against COVID-19, the VOICE study (1) enrolled 791 patients from multiple hospitals in the Netherlands in four distinct study groups comprising individuals without cancer, patients with cancer treated with immunotherapy, patients treated with chemotherapy and finally patients treated with a chemo-immunotherapy combination, to measure their responses to Moderna’s two-dose mRNA-1273 vaccine. At 28 days after administration of the second dose, adequate levels of antibodies to the virus in the blood were found in 84% of patients with cancer receiving chemotherapy, 89% of patients receiving chemo-immunotherapy in combination and 93% of patients on immunotherapy alone.
According to ESMO Press Officer Dr. Antonio Passaro, lung cancer expert at the European Institute of Oncology in Milan, Italy, not involved in the study, these results compare favourably with the antibody responses seen in almost all (99.6%) of the group of individuals without cancer: “The high rates of efficacy of the vaccine observed across the trial population, regardless of the type of anticancer treatment, constitute a strong and reassuring message for patients and their doctors,” he said.
Passaro further highlighted the importance of ensuring complete, two-dose vaccination for patients with cancer to develop enough protective antibodies against the virus, as the trial data also showed that only about one in three of those receiving chemotherapy on its own or in combination with immunotherapy had achieved a sufficient response after their first shot—half as many as in the group of individuals without cancer.
This observation was replicated in a study (2) on the effects of tozinameran (Pfizer–BioNTech) among 232 patients with cancer and 261 control subjects in Israel: while less than a third of individuals with cancer (29%) developed antibodies after receiving the first dose, compared to 84% in the control group, this proportion increased to 86% following administration of the second dose. Further demonstrating the efficacy of the vaccine, only two cases of COVID-19 were reported during the study period, both of which occurred in patients who had not yet received their second shot.
Booster shot could increase efficacy for more patients
Data from the CAPTURE study (3) presented today additionally shows that out of 585 patients with cancer having received two doses of either tozinameran or AstraZeneca’s COVID-19 Vaccine in the UK, those who had previously contracted COVID-19 (31%) had higher levels of virus-neutralising antibodies, including against variants such as Delta, for which vaccination loses some of its effectiveness. This is separately corroborated by research (4) showing that the antibody response to vaccination was significantly enhanced even after the first dose among patients with cancer who had recovered from COVID-19.
Dr. Luis Castelo-Branco, Medical Oncologist, ESMO Scientific and Medical Division, an expert with no ties to the studies, commented: “These findings lend additional support to the principle of offering the complete cycle, possibly including a third booster dose, to patients with cancer to improve their protection, because it suggests their immune system will respond to the extra stimulation.”
A study just published in the New England Journal of Medicine (5) has shown that a vaccination boost on people 60 years or older, after 5 months since completing their vaccination cycle, reduced the incidence of Covid-19 and severe illness.
“More data is needed to better understand for whom and when these vaccination boosts should be considered, but in general it would make sense to prioritise all patients with compromised immune function, including patients with cancer”
“Going forward, it will be important to continually reassess the vaccines’ effectiveness against new variants of SARS-CoV-2 as they emerge,” Castelo-Branco continued, emphasising that special consideration and additional protective measures should be provided to subgroups of patients such as those suffering from blood cancers, more than two thirds (69%) of whom were found in the CAPTURE study to have developed no neutralising antibodies at all against the currently dominant Delta variant following vaccination.
Vaccination against COVID-19 is safe for people with cancer
According to Castelo-Branco, these and other results presented at the ESMO Congress 2021, in reporting no new adverse events, offer conclusive evidence that while being largely effective, anti-COVID vaccination is just as safe for people with cancer as it is for the general population. This is notably demonstrated in a subgroup analysis (6) of 3,813 participants with a history of past or active cancer in the Phase III randomised controlled trial of tozinameran, which shows that the most common side-effects of vaccination were the same—injection-site pain, fatigue, fever, chills, headache and muscle pain—overwhelmingly mild and occurred at a similar frequency as within the overall trial population (44,047 participants).
“Although this trial excluded people on immune-function suppressing anticancer treatment such as chemotherapy, and thus a significant proportion of patients with cancer, taken together with the plethora of complementary data presented it contributes to a comprehensive and positive overall picture of COVID-19 vaccine efficacy and safety that the oncology community worldwide has good reason to rejoice over,” said Castelo-Branco.
ESMO President Solange Peters concluded: “Since the very start of the pandemic outbreak, we at ESMO have made it a top priority to secure extra care for our patients: first by educating oncology colleagues throughout these unprecedented events, then by pushing for the prioritisation of COVID-19 vaccination for patients with cancer. The ESMO promise of ‘Good Science. Better Medicine. Best Practice’ is kept once again, as the wealth of valuable data being presented at ESMO 2021 on the use of the anti-COVID vaccines in patients with cancer will allow us to provide practical guidance to the medical community—oncologists and other professionals alike—as well as inform decisions at the highest levels of health policymaking.”
Notes to Editors
Please make sure to use the official name of the meeting in your reports: ESMO Congress 2021
Official Congress Hashtag: #ESMO21
Data in this press release reflect the content of the abstracts highlighted. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.
1 Abstract LBA8 ‘Vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumours’ was presented by Sjoukje Oosting during Presidential symposium 3 on Monday 20 September, 15:05-16:35 (CEST) on Channel 1. Annals of Oncology, Volume 32, 2021 Supplement 5
2 Abstract 1559O ‘Efficacy and toxicity of BNT162b2 vaccine in cancer patients’ will be presented by Ithai Waldhorn during the Proffered Paper Session ‘SARS-CoV-2 and cancer’ on Tuesday 21 September, 13:30-14:50 (CEST) on Channel 5. Annals of Oncology, Volume 32, 2021 Supplement 5
3 Abstract 1557O ‘Adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients: The CAPTURE Study’ was presented by Scott Shepherd during Presidential symposium 3 on Monday 20 September, 15:05-16:35 (CEST) on Channel 1. Annals of Oncology, Volume 32, 2021 Supplement 5
4 Abstract 1563MO ‘CoVigi phase IV multicentric trial evaluating COVID-19 vaccination adverse events and immune response dynamics in cancer patients: First results on antibody and cellular immunity’ will be presented by Radka Obermannova during the Mini Oral Session ‘SARS-CoV-2 and cancer’ on Tuesday 21 September, 16:20-17:20 (CEST) on Channel 2. Annals of Oncology, Volume 32, 2021 Supplement 5
5 Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel Y.M. Bar-On et al
6 Abstract 1558O ‘COVID-19 vaccine in participants (ptcpts) with cancer: Subgroup analysis of efficacy/safety from a global phase III randomised trial of the BNT162b2 (tozinameran) mRNA vaccine’ will be presented by Stephen J. Thomas during the Proffered Paper Session ‘SARS-CoV-2 and cancer’ on Tuesday 21 September, 13:30-14:50 (CEST) on Channel 5. Annals of Oncology, Volume 32, 2021 Supplement 5
About the European Society for Medical Oncology (ESMO)
ESMO is the leading professional organisation for medical oncology. With more than 25,000 members representing oncology professionals from over 160 countries worldwide, ESMO is the society of reference for oncology education and information. Driven by a shared determination to secure the best possible outcomes for patients, ESMO is committed to standing by those who care about cancer through addressing the diverse needs of #ONEoncologycommunity, offering #educationforLIFE, and advocating for #accessiblecancerCARE. Visit www.esmo.org
LBA8 - Vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumors
S. Oosting1, A.A.M. Van der Veldt2, C.H. GeurtsvanKessel3, R.S.N. Fehrmann4, R.S. van Binnendijk5, A-M.C. Dingemans6, E.F.F. Smit7, T.J.N. Hiltermann8, G. den Hartog5, M. Jalving1, T. Westphal9, A. Battacharya1, M. van der Heiden10, C.U. Blank11, M.P. Koopmans3, C.A. van Els12, N.Y. Rots12, D. van Baarle13, J.B.A.G. Haanen14, E.G. de Vries1
1Medical Oncology Department, UMCG - University Medical Center Groningen, Groningen, Netherlands; 2Medical Oncology, Erasmus University Medical Center, Rotterdam, Netherlands; 3Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands; 4Department of Medical Oncology, University Hospital Groningen (UMCG), Groningen, Netherlands; 5Centrum voor Immunologie van Infectieziekten en Vaccins (IIV) Centrum voor Infectieziektebestrijding (Cib), RIVM: Rijksinstituut voor Volksgezondheid en Milieu, Bilthoven, Netherlands; 6Pulmonology Department, Erasmus MC - University Medical Center, Rotterdam, Netherlands; 7Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands; 8Department of Pulmonary diseases, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; 9Clinical Trials, IKNL, Utrecht, Netherlands; 10Medical Microbiology and Infection Prevention, UMCG - University Medical Center Groningen, Groningen, Netherlands; 11Medical Oncology Dept, NKI-AVL – Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands; 12Infectious Disease Control, RIVM: Rijksinstituut voor Volksgezondheid en Milieu, Bilthoven, Netherlands; 13Microbiology and Infection Prevention, UMCG – University Medical Center Groningen, Groningen, Netherlands; 14Medical Oncology Dept, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, Netherlands
Background: Patients with cancer have an increased risk of complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Vaccination is recommended, but the impact of chemotherapy and immunotherapy on immunogenicity and safety is still unclear.
Methods: This prospective multicenter non-inferiority trial comprises four cohorts: individuals without cancer (A) and patients with solid tumors who were treated with immunotherapy (B), chemotherapy (C) or chemo-immunotherapy (D). Participants received two mRNA-1273 vaccinations 28 days apart. The primary endpoint was SARS-CoV-2 Spike S1-specific IgG serum antibody response, defined as >10 binding antibody units (BAU)/ml 28 days after the second vaccination. We also assessed the virus neutralizing capacity of these antibodies, SARS-CoV-2 Spike-specific interferon-gamma T cell response, and adverse events.
Results: Of the 791 participants enrolled, 743 were evaluable for the primary endpoint in cohort A (n¼240), B (n¼131), C (n¼229) and D (n¼143). A SARS-CoV-2-binding antibody response was found in 100%, 99.3%, 97.4%, and 100% of the participants in cohorts A, B, C, and D, respectively. To discriminate between suboptimal and adequate responders, we defined a cut-off level at 300 BAU/ml, based on neutralizing capacity. The antibody response was considered adequate after the first vaccination in 66.0%, 37.1%, 32.5%, and 33.3% of the participants in cohorts A, B, C, and D, respectively. This raised 28 days after the second vaccination to respectively 99.6%, 93.1%, 83.8%, and 88.8% in cohorts A, B, C, and D. Spike-specific T cell responses were detected in 46.7% of suboptimal and non-responders. No new safety signals were observed.
Conclusions: mRNA-1273 vaccination is safe in the patient populations studied. For each cohort, the proportion of patients with a SARS-CoV-2-binding antibody response after two vaccinations is non-inferior compared to individuals without cancer. However, a significant minority lacks an adequate response. Most patients have an antibody concentration increase after the second vaccination. Therefore, an additional booster may turn inadequate into adequate responders.
Clinical trial identification: NCT04715438.
Legal entity responsible for the study: University Medical Center Groningen, the Netherlands.
Funding: ZonMw, The Netherlands Organisation for Health Research and Development.
Disclosure: All authors have declared no conflicts of interest
1559O - Efficacy and toxicity of BNT162b2 vaccine in cancer patients
I. Ben-Aharon1, I. Waldhorn1, R. Holland1, A. Peer1, M. Halberthal2, T.G. Goshen - Lago1
1Division of Oncology, Rambam Medical Center, Haifa, Israel; 2General Management, Rambam Medical Center, Haifa, Israel
Background: Efficacy and safety profile of COVID-19 vaccines had been acquired from phase III studies. Nevertheless, cancer patients were not represented in these trials. In 1/2021 mass vaccination of high-risk population, including cancer patients, was initiated in Israel. We aimed to prospectively evaluate efficacy, immunogenicity and safety of BNT162b2 vaccine in cancer patients.
Methods: Cancer patients on active treatment were prospectively enrolled following first dose of BNT162b2 or after a second dose. Serum was collected after each dose and additionally in case of seronegativity. An age-matched cohort of healthcare workers served as controls. Questionnaires regarding sociodemographics and adverse reactions were employed at serum collection. FDA-approved assay was used to assess IgG at all time-points. Patients’ electronic medical records were reviewed for documentation of COVID-19 infection, blood counts, liver enzymes and imaging studies.
Results: The study included 232 cancer patients and 261 controls. Following first dose 29% of patients were seropositive compared with 84% of controls (p<0.001). Following second dose seropositive rate reached 86%. Rate per 1000-person days after first dose were 12.5 for patients and 48.5 for controls. Chemotherapy reduced immunogenicity (OR 0.41 (95%CI 0.17-0.98). In seronegative patients, rate of documented leukopenia reached 39%. No COVID19 cases were documented throughout the study period except two cases following the first dose. Reported adverse events resembled former published studies.
Conclusions: Our results indicate the BNT162b2 appear to be safe and effective in cancer patients. There is a pronounced lag in antibody production compared with non-cancer controls, however seroconversion occurred in most patients after the second dose. Future real-world data is warranted to determine the long-term efficacy of the vaccine with regard to type of anti-cancer treatment.
Legal entity responsible for the study: The authors.
Disclosure: All authors have declared no conflicts of interest.
1557O - Adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients: The CAPTURE study
S.T.C. Shepherd1, A. Fendler2, L. Au2, F. Byrne2, K. Wilkinson3, M. Wu4, A.M. Schmitt5, N. Joharatnam-Hogan5, B. Shum5, L. Del Rosario5, K. Edmonds1, E. Carlyle1, E. Nicholson6, M. Howell4, C. Swanton7, S. Walker8, G. Kassiotis9, R. Wilkinson3, J. Larkin10, S. Turajlic2
1The Renal & Skin Unit, The Royal Marsden Hospital - NHS Foundation Trust, London, UK; 2Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK; 3Tuberculosis Laboratory, The Francis Crick Institute, London, UK; 4High Throughput Screening, The Francis Crick Institute, London, UK; 5Medical Oncology, The Royal Marsden Hospital - NHS Foundation Trust, London, UK; 6Haemato-Oncology, The Royal Marsden Hospital - NHS Foundation Trust, London, UK; 7Francis Crick Institute, London, UK; 8Department of Anaesthesia and Critical Care, The Royal Marsden Hospital – NHS Foundation Trust, London, UK; 9Retroviral Immunology Laboratory, The Francis Crick Institute, London, UK; 10Medicine, Royal Marsden Hospital NHS Foundation Trust, London, UK
Background: Patients with cancer are at increased risk of severe outcomes from COVID-19. Understanding the impact of SARS-CoV-2 infection and vaccination induced-immunity is an area of unmet need.
Methods: CAPTURE (NCT03226886) is a prospective longitudinal cohort study of COVID-19 vaccine or SARS-CoV-2 infection-induced immunity. SARS-CoV-2 infections were confirmed by RT-PCR and ELISA. Neutralising antibody titres (NAbT) against wild-type (WT) SARS-CoV-2 and variants of concern (VOC; Alpha, Beta, Delta) and SARS-CoV-2 specific T-cells (SsT-cells) were quantified.
Results: 118 patients (89% solid malignancy, [SM]) were SARS-CoV-2-positive (median follow-up: 154 days). 85% patients were symptomatic; 2 died of COVID-19. 82% had S1-reactive antibodies, of whom 89% had neutralising antibodies (NAbs); NAbT were lower against all VOCs. While S1-reactive antibody levels declined over time, NAbT remained stable up to 329 days. Most patients had detectable SsT-cells (76% CD4+, 52% CD8+). Haematological malignancy (HM) patients had impaired immune responses that were disease and treatment-specific (anti-CD20), but with evidence suggestive of compensation from T-cells. 585 patients were evaluated following 2 doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after 2 doses were 85% and 54% in patients with SM and HM, respectively. A lower proportion of patients had detectable NAbs against SARS-CoV-2 VOC (Alpha 62%, Beta 54%, Delta 49%) vs WT (84%), with corresponding significantly lower NAbT. Patients with HM were more likely to have an undetectable NAb and had lower NAbT vs solid malignancies to both WT and VOCs. Seroconversion showed poor concordance with NAbTs against VOCs. Prior SARS-CoV-2 infection boosted NAbT including against VOCs. Anti-CD20 treatment was associated with severely diminished NAbTs. Vaccine-induced T-cell responses were detected in 80% of patients, with no differences between vaccines or cancer types.
Conclusions: Patients with HM had blunted humoural responses to infection and vaccination, particularly against VOCs, but preserved cellular responses might contribute to protection. Our results lend support to prioritisation of all cancer patients for further booster vaccination.
Clinical trial identification: NCT03226886.
Legal entity responsible for the study: ThE Royal Marsden NHS Foundation Trust.
Funding: The Royal Marsden Charity; The National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at the Royal Marsden Hospital and Institute for Cancer Research (ICR).
Disclosure: All authors have declared no conflicts of interest.
1563MO - CoVigi phase IV multicentric trial evaluating COVID-19 vaccination adverse events and immune response dynamics in cancer patients: First results on antibody and cellular immunity
R. Obermannova1, R. Demlova2, I. Selingerova3, M. Doubek4, D. Okrouhlicova5, M. Mlnarikova6, K. Pilatova6, J. Nevrlka5, H. Lejdarova7, B. Weinbergerova8, Z. Cermakova9, D. Valik10, J. Mayer8, I. Kiss1, L. Zdrazilova-Dubska11
1Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic; 2Department of Pharmacology, Faculty of Medicine, Masaryk University, Department of Comprehensive Cancer Care, Masaryk University and Masaryk Memorial Cancer Institute, Brno, Czech Republic; 3Department of Laboratory Medicine, Department of Pharmacology, Medicine Faculty, Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech Republic; 4IHOK, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; 5Department of Laboratory Medicine, University Hospital Brno, Brno, Czech Republic; 6Department of Pharmacology, Department of Laboratory Medicine, University Hospital Brno, Brno, Czech Republic; 7Transfusion and Tissue Department, University Hospital Brno, Brno, Czech Republic; 8IHOK, University Hospital Brno and Faculty of Medicine, Masaryk University, University Hospital Brno, Brno, Czech Republic; 9Department of Laboratory Medicine, Masaryk Memorial Cancer Institute, Brno, Czech Republic; 10Department of Laboratory Medicine, University Hospital Brno, Brno, Czech Republic; 11Department of Pharmacology, Faculty of Medicine, Masaryk University, Department of Laboratory Medicine, University Hospital Brno, Brno, Czech Republic
Background: SARS-CoV-2 infection may be a threat for those undergoing active anticancer therapy. We aim to study adverse events, efficacy, and immune response in Covid-19 vaccinated patients focusing on possibly interfering therapy.
Methods: CoVigi is a prospective open-label multicentric phase 4 clinical study (EudraCT 2021-000566-14) enrolling patients on anti-cancer treatment. Vaccines from Pfizer-BioNTech, AstraZeneca, Johnson&Johnson, or Moderna are considered. Data on vaccination side effects, the onset and course of Covid-19, and quantitative analysis of anti-S and anti-N SARS-CoV-2 antibodies (Roche) and SARS-CoV-2 specific cellular response evaluated by IFN-gamma-release assay (Qiagen) and CD69 expression are recorded as follows: at the baseline (prior to the vaccination), prior to the 2nd dose, 4e8 weeks, 3, 6 and 12 months after the first dose.
Results: The trial was initiated on March 22th. As of May 4th, 152 solid cancer and 103 hematooncology patients were enrolled. From preliminary baseline data, 22% of solid cancer and 29% of hematooncology patients had detectable levels of anti-S antibodies with a median of 106 U/ml (range 1.4e3666) and 84 U/ml (range 0.75e2528), respectively (p ¼0.888). Surprisingly, only 44% solid cancer and 53% of hematooncology patients with detectable antibodies prior to the vaccination referred on covid-19 in medical history. In the Ab-positive cohort, the IFN-gamma level upon both CD4 and CD8 stimulation was 0.04 pg/ml (IQR 0.02e0.13), the CD69 expression on NKT-like cells increased to 10.9% (IQR 6.6e17.3), whereas in the Ab-negative cohort was 0.00 pg/ml (IQR 0.00e0.01 and to 7.5% (IQR 4.0e10.1), respectively (p <0.001 and p ¼0.079).
Conclusions: Substantial number of cancer patients experienced SARS-CoV-2 infection during active anti-cancer treatment prior to vaccination, often with asymptomatic course. In SARS-CoV-2-immunized patients, we observed SARS-CoV-2 positive cellular response. The preliminary results with dynamics of immune response with 3-month follow-up will be presented at the conference.
Acknowledgment: CZECRIN LM2018128, Roche Diagnostics, MMCI00209805, MHCZ/DRO (FNBr, 65269705).
Clinical trial identification: EudraCT 2021-000566-14.
Legal entity responsible for the study: Masaryk University.
Disclosure: All authors have declared no conflicts of interest.
1558O - COVID-19 vaccine in participants (ptcpts) with cancer: Subgroup analysis of efficacy/safety from a global phase III randomized trial of the BNT162b2 (tozinameran) mRNA vaccine
S.J. Thomas1, J.L. Perez2, S.P. Lockhart3, S. Hariharan4, N. Kitchin3, R. Bailey3, K. Liau5, E. Lagkadinou6, Ö. Türeci7, U. Şahin7, X. Xu8, S.S. Dychter9, C. Lu10, T. Gentile11, W. Gruber10
1Institute for Global Health and Translational Sciences, State University of New York, Upstate Medical University, Syracuse, NY, USA; 2Vaccine Research and Development, Pfizer, Collegeville, PA, USA; 3Vaccine Research and Development, Pfizer, Maidenhead, UK; 4Oncology, Pfizer, New York, NY, USA; 5Pfizer, La Jolla, CA, USA; 6Clinical Research, Clinical Development, BioNTech SE, Mainz, Germany; 7BioNTech SE, Mainz, Germany; 8Biostatistics, Pfizer, Collegeville, PA, USA; 9Global Product Development, Pfizer, San Diego, CA, USA; 10Vaccine Research and Development, Pfizer, Pearl River, NY, USA; 11State University of New York, Upstate Medical University, Syracuse, NY, USA
Background: Patients with cancer are at higher risk of developing COVID-19 disease, adverse outcomes, and increased mortality. Phase III COVID-19 vaccine trials have demonstrated safety/efficacy against COVID-19 and prevented hospitalizations and deaths; however, most excluded ptcpts with cancer. We present phase 3 tozinameran mRNA COVID-19 vaccine trial results from ptcpts with a cancer history at baseline, either ongoing or not, per the Charlson Comorbidity Index and up to 6 months of follow-up.
Methods: Between Jul 2020-Jan 2021, 46429 ptcpts 12 y at 152 sites in 6 countries were randomized in a placebo-controlled, observer-blinded trial of 2-dose tozinameran, showing 95% protection against COVID-19 and favorable safety (Polack et al NEJM, Dec 2020). After emergency use authorization, ptcpts were allowed to unblind and placebo recipients received vaccine. Data prior to unblinding for crossover up to 13 Mar 2021 are presented for ptcpts 16 y for safety and 12 y for efficacy. Adverse event (AE) data are controlled for follow-up time before unblinding and reported as incidence rate (IR) per 100-person-y of follow-up.
Results: Of ptcpts 16 y, 1647 had a prior diagnosis of cancer and were not on active immunosuppressive treatment (755 M; 892 F; median age 66 y [range 22-91]). Most common solid cancers included breast (n¼458), prostate (n¼360), and melanoma (n¼210). AEs were reported at IRs of 94.0 (vaccine) and 49.3 (placebo) per 100-person-y; most common AEs were reactogenicity events (injection-site pain [IR: 40.2 vaccine; 4.2 placebo]; fatigue [IR: 21.4 vaccine; 7.6 placebo]; pyrexia [IR: 19.8 vaccine; 0.7 placebo]). 1 vaccine ptcpt withdrew due to a vaccine-related AE. No vaccine-related deaths were reported. Among ptcpts 12 y with cancer, 3 vaccine and 27 placebo recipients developed COVID-19 from 7 days post-Dose 2; vaccine efficacy (VE) was 89.7% (95% CI 66.5-98.0%). This compares favorably with overall VE of 91.1%. Updated results will be presented.
Conclusions: Tozinameran has similar efficacy/safety in ptcpts with cancer as in the overall population. These results inform tozinameran use in COVID-19 and in future trials in patients with cancer.
Clinical trial identification: NCT04368728.
Editorial acknowledgement: Editorial assistance was provided by Erin Bekes, PhD, of CMC AFFINITY, McCann Health Medical Communications, and was funded by Pfizer.
Legal entity responsible for the study: Study sponsored by BioNTech, managed by Pfizer.
Funding: Pfizer and BioNTech.
Disclosure: S.J. Thomas: Financial Interests, Personal and Institutional, Research Grant, Advisory role: Pfizer. J.L. Perez: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. S.P. Lockhart: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. S. Hariharan: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. N. Kitchin: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. R. Bailey: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. K. Liau: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. E. Lagkadinou: Financial Interests, Personal, Full or part-time Employment: BioNTech. Ö. Türeci: Financial Interests, Personal, Research Grant: BioNTech. U. S ̧ahin: Financial Interests, Personal, Research Grant: BioNTech. X. Xu: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. S.S. Dychter: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. C. Lu: Financial Interests, Personal, Full or part-time Employment: Pfizer. W. Gruber: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Pfizer. All other authors have declared no conflicts of interest.
Annals of Oncology