Immunogenicity of SARS-CoV-2 vaccines in patients with breast cancer receiving CDK 4/6 inhibitors

ABSTRACT

Background: CDK 4/6 inhibitors have transformed the landscape of breast oncology. A CDK 4/6 inhibitor in combination with endocrine therapy is recommended as 1st line therapy for patients with metastatic hormone receptor positive breast cancer. CDK 4/6 inhibitors have purported immunomodulatory effects and while effective, myelosuppression is a common adverse effect of CDK 4/6 inhibitor treatment of breast cancer. The impact of CDK 4/6 inhibitor therapy on immunogenicity of vaccines is not known. In this study, we evaluated the spike antibody response to SARS-CoV-2 vaccines among patients with breast cancer receiving endocrine therapy with or without CDK 4/6 inhibitors. Methods: In the Cancer COVID and Vaccine (CANVAX) study eligible patients included patients with breast cancer who had completed all scheduled doses of SARS-CoV-2 vaccines. Chart review was conducted to identify patients who had received endocrine therapy with or without CDK 4/6 inhibitor. We used validated assays to measure anti-SARS-CoV-2 total IgA/M/G spike antibodies and virus neutralization. We evaluated the magnitude of antibody response based on geometric mean concentrations (GMCs) as well as the % of patients with inadequate seroconversion (defined as levels <100 U/ml). Independent T-test based on log-transformed antibody values was utilized to compare the spike antibody levels and p value of ≤ 0.05 Swas considered statistically significant. Results: Between April 2021 and June 2021, 203 patients with breast cancer were enrolled. As of the cut-off date (2nd July 2021), results were available for 73 patients treated with endocrine therapy alone (N = 23), or with CDK 4/6 inhibitor-based therapy (N = 50). Most were females (98.6%), white (83.6%), and had metastatic breast cancer (68.5%). 49.3% had received BNT162b2 (Pfizer), 37% mRNA1273 (Moderna), and 13.7% Ad26.COV2.S (Johnson and Johnson/Janssen) vaccines. Overall, the mean spike antibody levels were similar between patients treated with endocrine therapy alone vs CDK 4/6 inhibitor-based therapy (GMC 326 vs. 719 U/mL;p=0.704). Mean spike antibody levels were higher in patients with early breast cancer vs. metastatic breast cancer (GMC 555 vs. 465 U/mL;p=0.031). However, patients who received Ad26.COV2.S had lower levels of mean spike antibody levels (GMC 47 U/ml), compared with patients treated with BNT162b2 (GMC 400 U/ml) or mRNA1273 (GMC 2203 U/mL;P<0.01 for both comparisons). Comparison of neutralization titers in 66 individuals supported the above results. 11 (15.1%) patients had low antibody titers (<100U/ml) of seroconversion and 3 received a booster vaccine, with 1 having available repeat titer results thus far demonstrating a significant improvement. Conclusions: The majority of patients receiving CDK 4/6 inhibitor have adequate antibody response to SARS-CoV-2 vaccines, particularly mRNA vaccines. However, a minority of patients may require booster vaccine to augment immunity. Monitoring spike antibody levels could be helpful to identify patients with inadequate seroconversion and guide mitigation strategies for patients with breast cancer.