Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Comment premature deaths have been mainly seen in high- Knowledge, Advocacy and Policy (SJ, ZT, YR) and Special Projects (JT), Union for International Cancer Control, Geneva 1202, Switzerland; City Cancer income countries. Disruptions caused by the COVID-19 Challenge, Geneva, Switzerland (SF); Division of Human Health, Department pandemic—more than 40% of countries report of Nuclear Sciences and Applications (MA-W) and Division of Programme of Action for Cancer Therapy, Department of Technical Cooperation (AJ, LS), partially or fully disrupted cancer services—are now International Atomic Energy Agency, Vienna, Austria; Cancer Surveillance expected to further exacerbate disparities in access Section, International Agency for Research on Cancer, Lyon, France (FB, MP); Supportive Oncology program and IU Simon Cancer Center, Indiana University to cancer care and increase excess mortality.10 There School of Medicine, Indianapolis, IN, USA (JC); Prevention, Treatment and must be renewed commitment to, and investments Rehabilitation Unit, Drug Prevention and Health Branch, United Nations Office on Drugs and Crime, Vienna, Austria (EM); and Department of in, cancer control that spurs greater action and Non-Communicable Diseases, WHO, Geneva, Switzerland (AI, BM) integration at all service levels, particularly primary 1 Adams C, Torode J, Henshall S, Cazap E, Ryel AL, Grey N. The World Cancer care for prevention, early detection and palliative care, Declaration: from resolution to action. Lancet Oncol 2011; 12: 1091–92. 2 WHO. Assessing national capacity for the prevention and control of which also offer benefits in the broader prevention and noncommunicable diseases: report of the 2019 global survey. Geneva: control of non-communicable diseases. World Health Organization, 2020. 3 Bruni L, Diaz M, Barrionuevo-Rosas L, et al. Global estimates of human Governments must include cancer interventions papillomavirus vaccination coverage by region and income level: a pooled analysis. Lancet Glob Health 2016; 4: 453–63. in universal health coverage as essential health 4 WHO. Report on the global tobacco epidemic, 2019: offer to help to quit services, with associated financial protection from tobacco use: executive summary. Geneva: World Health Organization, 2019. the catastrophic expenditure experienced by so many 5 Guthold R, Stevens GA, Riley LM, Bull FC. Global trends in insufficient patients with cancer. The vision of the World Cancer physical activity among adolescents: a pooled analysis of 298 population-based surveys with 1·6 million participants. Declaration is still relevant and, to succeed in achieving Lancet Child Adolesc Health 2020; 4: 23–35. its targets, we must do more. Millions of lives depend 6 International Agency for Research on Cancer. World cancer report: cancer research for cancer prevention. In: Wild CP, Weiderpass E, on it. Stewart BW, eds. Lyon: International Agency for Research on Cancer, 2020. We declare no competing interests. FB, AI, BM, and MP are staff members of 7 Union for International Cancer Control. International public opinion WHO. The authors alone are responsible for the views expressed in this survey on cancer. Geneva: Union for International Cancer Control, 2020. Comment and they do not necessarily represent the decisions, policy, 8 Abdel-Wahab M, Zubizarreta E, Polo A, Meghzifene A. Improving quality or views of WHO. and access to radiation therapy—an IAEA perspective. Semin Radiat Oncol © 2021 World Health Organization. Published by Elsevier Ltd. All rights 2017; 27: 109–17. reserved. 9 Worldwide Hospice Palliative Care Alliance, WHO. Global atlas of palliative care, 2nd edn 2020. http://www.thewhpca.org/resources/ *Sonali Johnson, Zuzanna Tittenbrun, Yannick Romero, global-atlas-on-end-of-life-care (accessed Dec 1, 2020). Julie Torode, Silvina Frech, May Abdel-Wahab, Arsen Juric, 10 WHO. The impact of the COVID-19 pandemic on noncommunicable disease resources and services: results of a rapid assessment. Geneva: Lisa Stevens, Freddie Bray, Marion Piñeros, James Cleary, World Health Organization, 2020. Elizabeth Mattfeld, André Ilbawi, Bente Mikkelsen johnson@uicc.org SARS-CoV-2 vaccination and phase 1 cancer clinical trials There is now a rapid global roll-out of severe acute tolerability, although the durability of protection, and respiratory syndrome coronavirus 2 (SARS-CoV-2) thus the need for repeated vaccinations, is uncertain. vaccines as part of the response to the COVID-19 COVID-19-associated morbidity and mortality in Daniela Beckmann/Science Photo Library pandemic.1 Approved SARS-CoV-2 vaccines include patients with cancer range from 5% to 61% based those from Pfizer-BioNTech,2 Moderna,3 and Oxford– on data from the COVID-19 and Cancer Consortium AstraZeneca,4 but WHO estimates that there are registry and other groups, more than the 2–3% 52 ongoing clinical research projects developing observed in the general population.1 Although these SARS-CoV-2 vaccines.1 Different vaccine mechanisms morbidity and mortality figures are associated with have been explored using technologies based confounding biases, it is clear that patients with Published Online on messenger RNA (mRNA), synthetic long viral cancer are vulnerable and have a high risk of serious February 8, 2021 https://doi.org/10.1016/ peptides, plasmid DNA, and inactivated, attenuated, COVID-19 symptoms. The efficacy of SARS-CoV-2 S1470-2045(21)00017-6 or genetically modified viruses. Efficacy data are vaccines is likely to vary between patients depending encouraging, with the mRNA-based vaccines reporting on cancer type, disease burden, comorbidities, and more than 90% protection from COVID-19 with good intrinsic or therapy-induced immunosuppression. 298 www.thelancet.com/oncology Vol 22 March 2021 Comment To the best of our knowledge, SARS-CoV-2 vaccine Panel: Recommendations for SARS-CoV-2 vaccination and trials have excluded patients in anticancer trials or phase 1 cancer trials taking immunosuppressive drugs, which limits formal Not started phase 1 trial experience in this area and means that further data Avoid starting trial investigational medicinal product (IMP) are needed to address concerns regarding the effects until 2–4 weeks after the second dose of severe acute of malignancies and anticancer drugs on vaccine respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is administered safely for trial IMPs with cytokine release efficacy. Although policies covering the optimisation syndrome risk. of the timing of vaccinations during standard-of- care chemotherapy, tumour-cell targeted drugs, Already in phase 1 trial Administer SARS-CoV-2 vaccine during the phase 1 trial but immunotherapy, radiotherapy, and surgery are being avoid vaccination on days of parenteral IMP dosing and the introduced, it is unlikely that there will be any formal dose-limiting toxicity period. guidance on experimental phase 1 clinical trials of investigational medicinal products (IMPs).5,6 This is especially pertinent for first-in-human, first-in-class vaccination has depended on the individual patient phase 1 trials of novel anticancer drugs, in which and the type of trial therapy; for example, vaccinations toxicity and efficacy profiles are limited to preclinical are recommended before systemic trial therapies in-vitro and in-vivo data. commence, and are generally permitted on trial if the In general, with regards to phase 1 trials of anticancer patient has already started systemic therapy. However, drugs, two key questions arise: what are the potential guidance on the administration of SARS-CoV-2 effects of such IMPs on (1) the efficacy and (2) the vaccines from trial sponsors has been unclear, ranging toxic effects of SARS-CoV-2 vaccinations; and vice from full approval for such vaccines to be given in versa. For example, a SARS-CoV-2 vaccine is likely to parallel to the IMP, to a complete avoidance of the confer reduced protection in patients participating vaccine during IMP administration. in phase 1 trials of experimental B cell-depleting We are an international group of medical oncologists antitumour drugs, such as monoclonal antibodies based across the USA, the UK, Canada, and Europe targeting CD10, CD19, or CD20, or CD19 chimeric and are involved in treating patients with advanced antigen receptor T cells, given that such patients are cancers in early phase clinical trials. On the basis of unlikely to mount an optimal immune response.7 the promising clinical data for approved SARS-CoV-2 From experience with influenza A vaccinations in vaccines, we believe that the benefits of vaccination patients receiving checkpoint inhi­bitors targeting PD- in the COVID-19 pandemic should substantially 1 or PD-L1, seroconversion and sero­protection rates outweigh the possible benefits of participating in a are generally high.8 Toxicity is particularly important phase 1 trial in light of the high risk to these patients when considering the effects of vaccinations on trials of contracting life-threatening SARS-CoV-2 infection. that involve IMPs with a high risk of immune adverse We believe that any unnecessary delays with SARS- events, including cytokine release syndrome, or novel CoV-2 vaccination should be avoided. We recommend drugs given in combination with immunotherapies. applying risk stratification by considering trials Although there is experience in administering well with a risk of cytokine release syndrome (eg, certain established vaccinations to patients with cancer in immunotherapies) separately to those without such phase 1 trials, these tend to be limited to inactivated toxicities (eg, non-immunotherapy studies involving vaccines and exclude live-attenuated and replication- molecularly targeted drugs). We also recommend that competent vector vaccines. This contrasts with the patients participating in early trials of anticancer drugs available SARS-CoV-2 vaccines that are mRNA-based, with unknown safety and tolerability should avoid live attenuated, non-replicating, or that use more starting trial IMPs until 2–4 weeks after the second conventional protein subunits. dose of the SARS-CoV-2 vaccine is administered The COVID-19 pandemic requires consideration of safely, especially for those with a risk for cytokine when patients participating in early cancer clinical release syndrome (panel). If the trial involves proven trials should get vaccinated.5 Typically, the timing of anticancer drugs with known benefits, this wait might www.thelancet.com/oncology Vol 22 March 2021 299 Comment be more challenging for patients with progressing safe doses for future studies, the potential benefit advanced cancers, and the risks and benefits of the to patients is well described.10 These factors need to delay must be carefully considered with the patient. be judiciously balanced with the unknown effects We also recommend that patients avoid receiving their of the IMP on SARS-CoV-2 vaccination and the risk vaccine on days of parenteral IMP dosing (and receive of such vaccines worsening the toxicity of a subset it at a time as distanced as possible from IMP dosing) of novel anticancer drugs. Patient motivations and and the dose-limiting toxicity period if administration expectations of phase 1 oncology trials are varied. It of the SARS-CoV-2 vaccine is mandated while the will therefore be essential for decisions to be made on patient is participating in an early phase trial. This an individual basis with patients and their advocates to latter strategy will minimise the risk of confounding assess the risk–benefit balance by considering known overlapping or added adverse events during the crucial IMP mechanisms and adverse events, and key patient trial period of the IMP. This is particularly pertinent for characteristics, such as age, comorbidities, prognosis, common SARS-CoV-2 vaccine adverse events, such as and social factors. This is an opportunity for, and tiredness, headaches, muscle and joint aches, chills, indeed a duty of, treating oncologists, trial sponsors, and fever, which might be particularly prominent after and regulatory agencies to monitor, document, and the second vaccine dose or if the patient has already communicate outcomes of the different SARS-CoV-2 been exposed to asymptomatic SARS-CoV-2 infection. vaccines during anticancer drug administration, as Close monitoring of patients in real time after well as their effect on the development of COVID-19, SARS-CoV-2 vaccination will be essential to assess toxicity of anticancer drugs, and eventual cancer potential interactions, adverse events, and clinical outcomes. As the vaccination programmes roll out outcomes, including those from both SARS-CoV-2 globally, this early experience is likely to affect the infection and complications from cancer. In patients timing, safety, and efficacy of SARS-CoV-2 vaccination who have cancer trial IMP-associated immune-related for a considerable period. adverse events, such as colitis or pneumonitis, and We declare no competing interests related to the study, with full details of See Online for appendix other competing interests listed in the appendix. TAY thanks the are on steroids or other immunosuppressive drugs, MD Anderson Cancer Center for support grant P30 CA016672 and the the SARS-CoV-2 vaccine should probably be avoided Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy at the MD Anderson Cancer Center for support grant 1U01 CA180964. until the event is fully resolved or markedly improved. RP, JSDB, and UB thank the Experimental Cancer Centre and National Institute Clearly, such decisions need to be individualised to of Health Biomedical Research Centre for infrastructural funding. each patient and IMP risk profile. *Timothy A Yap, Lillian L Siu, Emiliano Calvo, Because it is currently unclear how long immunity Martijn P Lolkema, Patricia M LoRusso, Jean-Charles Soria, will last after vaccination, with this response likely Ruth Plummer, Johann S de Bono, Josep Tabernero, to be temporary and lasting months to years, rather Udai Banerji tyap@mdanderson.org than decades or a lifetime, repeat vaccinations are Investigational Cancer Therapeutics (Phase I Program), University of Texas MD likely to be required during a patient’s lifetime. Anderson Cancer Center, Houston, TX 77030, USA (TAY); Division of Medical Repeat vaccination decisions will therefore require Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada (LLS); Early Phase Clinical Drug consideration of any changing risk factors. SARS- Development in Oncology, START Madrid-CIOCC, Centro Integral Oncológico CoV-2 infection has no doubt affected and delayed all Clara Campal, Madrid, Spain (EC); Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, components of care for patients with cancer, including Rotterdam, Netherlands (MPL); Early Phase Clinical Trials Program, Yale screening, diagnosis, treatment, and monitoring and University Medical Center, New Haven, CT, USA (PML); Department of Drug Development, Gustave Roussy Cancer Institute, University Paris Saclay, surveillance strategies, and has probably increased the Villejuif, France (J-CS); Northern Institute for Cancer Care, Freeman Hospital risk of cancer-related morbidity and mortality.9 The and Newcastle University, Newcastle upon Tyne, UK (RP); The Institute of Cancer Research, London, UK (JSdB, UB); Royal Marsden NHS Foundation pandemic also affects oncology trials, including patient Trust, London, UK (JSdB, UB); Department of Medical Oncology, Vall d’Hebron accrual and logistical and economic aspects, and has Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain (JT) the potential to affect the long-term development of 1 European Society for Medical Oncology. ESMO statements for promising life-saving anticancer drugs. vaccination against COVID-19 in patients with cancer. https://www. esmo.org/covid-19-and-cancer/covid-19-vaccination (accessed Although phase 1 oncology trials have unknown Jan 7, 2021). toxicity risks and are done primarily to recommend 300 www.thelancet.com/oncology Vol 22 March 2021 Comment 2 Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the 7 Yri OE, Torfoss D, Hungnes O, et al. Rituximab blocks protective BNT162b2 mRNA COVID-19 vaccine. N Engl J Med 2020; 383: 2603–15. serologic response to influenza A (H1N1) 2009 vaccination in lymphoma 3 Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against patients during or within 6 months after treatment. Blood 2011; SARS-CoV-2—preliminary report. N Engl J Med 2020; 383: 1920–31. 118: 6769–71. 4 Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the 8 Bayle A, Khettab M, Lucibello F, et al. Immunogenicity and safety of ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim influenza vaccination in cancer patients receiving checkpoint inhibitors analysis of four randomised controlled trials in Brazil, South Africa, and targeting PD-1 or PD-L1. Ann Oncol 2020; 31: 959–61. the UK. Lancet 2020; 397: 99–111. 9 Sud A, Torr B, Jones ME, et al. Effect of delays in the 2-week-wait cancer 5 Curigliano G, Banerjee S, Cervantes A, et al. Managing cancer patients referral pathway during the COVID-19 pandemic on cancer survival in the during the COVID-19 pandemic: an ESMO multidisciplinary expert UK: a modelling study. Lancet Oncol 2020; 21: 1035–44. consensus. Ann Oncol 2020; 31: 1320–35. 10 Adashek JJ, LoRusso PM, Hong DS, Kurzrock R. Phase I trials as valid 6 Society for Immunotherapy of Cancer. SITC statement on SARS-CoV-2 therapeutic options for patients with cancer. Nat Rev Clin Oncol 2019; vaccination and cancer immunotherapy. https://www.sitcancer.org/ 16: 773–78. aboutsitc/press-releases/2020/sitc-statement-sars-cov-2-vaccination- cancer-immunotherapy (accessed Jan 7, 2021). Quality assurance and cancer medicines in low-income and middle-income countries Substandard medicines are medicines that fail to meet physical pain, or are worried about becoming a financial their quality standards, whereas falsified medicines burden on their families.4 Access to quality-assured are those that have been deliberately misrepresented medicines is integral to tackling inequality in cancer in their identity, composition, or source.1 Both outcomes and for fostering a global patient-centred substandard and falsified medicines are a major burden public health approach, which has increasingly been on health and economic outcomes, particularly in called for during the COVID-19 pandemic.5 low-income and middle-income countries (LMICs).1 Delivery of quality-assured medicines at the point WHO reports that one in ten medicines in LMICs might of access requires a robust regulatory system. When be substandard or falsified,1 although a systematic the regulatory system is deficient, substandard or review suggests higher rates of 11–48%.2 These falsified medicines can be accessed through formal medicines impact a broad range of therapies, including supply routes that serve public facilities. Although cancer treatments, antibiotics, and other life-saving initiatives between high-income countries and LMICs therapies.1 are helping to strengthen regulatory control,1 challenges There is vast global inequality in cancer outcomes,3 related to a scarcity of testing facilities, regulatory which is attributed to factors such as sparse imple­ workforce and expertise, oversight, administration, and mentation of prevention strategies, delayed diagnosis, communications still exist.6 and difficulty accessing treatment. Cancer control requires There is a need to simultaneously strengthen the early diagnosis, effective intervention, and palliative care.3 formal supply chain workforce to maintain the quality Treatment of cancer often leads to catastrophic financial costs for patients and their families,3 which exacerbates existing income inequalities, hinders socioeconomic progress in marginalised groups, and causes poverty cycles.4 These impacts are compounded by the infiltration of substandard or falsified medicines into health-care settings. The out-of-pocket spending and indirect costs of cancer (eg, due to work loss) increase if patients purchase ineffective medicines. Substandard or falsified medicines reduce patient LuchschenF/Shutterstock confidence in health-care systems, which can lead to disengagement if patients do not perceive effective treatments to be available, or if they fear prolonged www.thelancet.com/oncology Vol 22 March 2021 301