ASCO Calls for Inclusion of Individuals With Cancer on COVID-19 Vaccine Trials

Everett E. Vokes, MD, FASCO

Individuals with cancer or who have a history of cancer should qualify for inclusion on COVID-19 vaccine trials, unless there is a safety justification for exclusion, according to a joint position statement released by ASCO and Friends of Cancer Research.^1,2

The clinical trials examining vaccines to protect against COVID-19 that have been conducted to date have universally excluded patients with cancer from participation, and several have excluded those with a history of cancer.

Because these efforts have included a narrower scope of patients, it is not fully known whether the vaccines that have been authorized for emergency use are safe and effective for patients with cancer—especially those with comorbidities, who are most vulnerable to the virus. This gap in knowledge represents a risk for these patients and society.

“We’ve learned that patients with cancer are especially vulnerable to severe illness, hospitalization, or death due to COVID-19,” Everett E. Vokes, MD, FASCO, president of ASCO, stated in a press release. “However, since clinical trials for COVID-19 vaccines have largely excluded patients with cancer, we still have a long way to go to better understand how safe and effective COVID-19 vaccines are for patients in active treatment. It is critically important to study adequate numbers of patients who have cancer or a history of cancer so that we can better understand the degree to which patients with cancer, various kinds of immunocompromise, or both respond to vaccines.”

In December 2020, the FDA issued the first emergency use authorization (EUA) to the Pfizer-BioNTech COVID-19 vaccine for the prevention of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals who were at least 16 years of age.³ In May 2021, the EUA was expanded to include adolescents between 12 and 15 years of age.

Efficacy data to support the EUA included information yielded from an analysis that looked at 36,523 individuals who were included in a randomized, placebo-controlled, global study.⁴ Most participants resided in the United States and did not showcase evidence of SARS-CoV-2 infection through 7 days following the second vaccine dose.

Of all individuals examined, 18,198 received the vaccine and 18,325 were given placebo. Results revealed that the vaccine was 95% effective in preventing infection with the virus. Only 8 individuals in the investigative arm were infected with COVID-19 vs 162 in the placebo arm. Of the total 170 COVID-19 cases reported, only 1 in the investigative arm and 3 in the placebo arm were determined to be severe.

Later that month, the FDA issued another EUA to the Moderna COVID-19 vaccine, which was supported by results from an analysis of 28,207 individuals included on a randomized, placebo-controlled study done in the United States.⁴ Individuals did not have evidence of SARS-CoV-2 prior to their first vaccine dose. Among the participants, 14,134 were administered the vaccine and 14,073 received placebo. Here, the vaccine was found to be 94.1% effective in preventing the virus, with 11 COVID-19 cases reported in the investigative arm and 185 cases reported in the placebo arm.

The most recent vaccine to be issued an EUA from the regulatory agency, in February 2021, is the Janssen COVID-19 vaccine.⁵ Efficacy data were yielded from an analysis of 39,321 individuals who were included in a randomized, placebo-controlled study done in South Africa, select countries in South America, Mexico, and the United States. Of all participants, 19,630 received the vaccine and 19,691 were given placebo. The vaccine was found to be about 67% effective in preventing moderate to severe/critical infection with the virus at least 14 days following vaccination. Moreover, the vaccine was 66% effective in preventing moderate to severe/critical infection at least 28 days following vaccination.

Recommendations for vaccination of patients with cancer, particularly those who were receiving active treatment for their disease, are currently based on consensus expert opinion in the absence of clinical evidence, according to ASCO. The field is awaiting more evidence from several ongoing studies may provide more specific insights and guidance about vaccination in these populations.

Based on real-world evidence in patients with cancer, the CDC has included cancer as a high-risk condition that predisposes patients to severe illness with the virus in their guidance. As such, organizations such as ASCO and ESMO, among others, recommend that these patients be vaccinated against the virus, unless it is specifically contraindicated.

Importantly, patients with cancer are often discouraged from receiving vaccines that utilize live viruses as they tend to be immunocompromised and receiving such a vaccine could potentially put them at risk for viral transmission and infection. However, none of the vaccines that have been authorized contain live viruses.

“Exclusion of patients with cancer from clinical trials without scientific justification (ie, evidence of potential risk to patient safety) disproportionately impacts certain patient groups and patients with certain disease characteristics,” representatives wrote in the joint position statement. “Furthermore, lack of affirmative safety and efficacy data in patients with cancer compromises the ability to provide evidence-based counseling on the level of protection offered by COVID-19 vaccine in this vulnerable patient population. Therefore, unjustified exclusion compromises equity and inclusivity in addition to clinical decision-making.”

The organizations note that there are many existing questions pertaining to the optimal use of the COVID-19 vaccine in patients with cancer who are immune-suppressed or who are on immune-modulating treatment for their disease. They argue that if specific concerns regarding immunogenicity and efficacy for a vaccine exist, then the inclusion of those patient cohorts in prospective clinical trials should be a priority consideration.

Moreover, more data are needed regarding ideal timing between cycles of therapy or length of waiting periods following stem cell transplants or immune globulin therapy with respect to COVID-19 vaccine administration.

Although limited, available data suggest that patients with cancer may experience substantial responses to the COVID-19 vaccines. However, more safety and efficacy data for patients with cancer or who have a history of cancer who are receiving one of the COVID-19 vaccines are needed, as are data on how therapies used in these populations may impact response to the vaccine.

In the joint position statement, the organizations recommend the following:

• Sponsors of vaccine trials should design studies to be as broadly inclusive as possible. Existing and future trials examining these products should only exclude patients with cancer and those who are immunocompromised if there is a specific risk of harm to them.
• Vaccine manufacturers and trial sponsors should prioritize the recruitment of patients with cancer by partnering with oncology practices, cancer centers, and academic medical centers. Vaccine trials should be prospectively designed and purposefully recruit sufficient numbers of patients with cancer from diverse populations and age groups to enable valid subset analysis.
• Government agencies with oversight of vaccine development and review should encourage and incentivize vaccine manufacturers to include patients with cancer in existing and future trials examining their COVID-19 vaccination products.
• Public health agencies and other research organization should design, collect, and examine real-world data on vaccine effectiveness in patients with cancer, in addition to data yielded on clinical trials. For populations that are underrepresented on prior vaccination trials, this data collection could enable the most comprehensive understanding of practical clinical considerations.

References

1. Individuals with cancer must be included in COVID-19 vaccine trials: new ASCO-Friends joint position statement encourages enrollment of patients with cancer in vaccine studies. News release. ASCO. June 22, 2021. Accessed June 23, 2021. https://bit.ly/3h0cepL
2. Inclusion of individuals with cancer on COVID-19 vaccine trails: a joint position statement from the American Society of Clinical Oncology and Friends of Cancer Research. ASCO and Friends of Cancer Research. Accessed June 23, 2021. https://bit.ly/3qlB87x
3. FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine. News release. FDA. December 11, 2020. Accessed June 23, 2021. https://bit.ly/3gWWfsE
4. FDA takes additional action in fight against COVID-19 by issuing emergency use authorization for second COVID-19 vaccine. News release. FDA. December 18, 2020. Accessed June 23, 2021. https://bit.ly/34IwcjR
5. FDA issues emergency use authorization for third COVID-19 vaccine. News release. FDA. February 27, 2021. Accessed June 23, 2021. https://bit.ly/2TZuhEY