Background: The treatment of cancer was profoundly disrupted by COVID-19. Although there were well-documented impacts on cancer screening and surgery, the precise effect on treatment patterns with systemic therapy in the Medicare population has not been described. Methods: This study analyzed the 100% Medicare Research Identifiable Files (2017-2022) for patients with breast cancer, colorectal cancer, lung cancer, prostate cancer, and lymphoma who received antineoplastic therapy under either the Part B or Part D benefit setting. We examined patient demographics, patient diagnoses, treatment regimens, and Total Cost of Care (TCOC) (per month on treatment). Patients were selected for analysis if they had 12 months of continuous enrollment in Medicare Parts A, B, and D within the calendar year, and at least 2 claims of the same therapy within 60 days. Demographic information was attributed from the Master Beneficiary Summary File (MBSF). Results: Prior to the pandemic, 14% of breast cancer patients, 16% of colorectal cancer patients, 34% of lung cancer patients, 25% of lymphoma patients and 12% of prostate cancer patients received systemic therapy. During the pandemic, the number of Medicare beneficiaries with a cancer diagnosis decreased in all diagnosis groups. In addition, during the peak year of the COVID pandemic (2020), the proportion of beneficiaries receiving therapy decreased as well, ranging from -3% (lymphoma) to -9% (colorectal). This decrease was uniform across race and socio-economic indicators (LIS beneficiary or dually enrolled in Medicare/Medicaid). For four of the cancer types (breast, colorectal, lung, and prostate), the average number of months on therapy in 2020 slightly increased for chemotherapy. Across all cancer types and treatment types, the average per month TCOC increased during in 2020. Conclusions: Treatment of cancer was disrupted by COVID-19. A smaller number of Medicare beneficiaries were diagnosed with cancer and of these, a smaller percent received systemic treatment. Of those treated, time on treatment was slightly longer and TCOC was slightly higher. These effects were seen to the same extent in all examined sociodemographic groups. The pandemic certainly impacted the systemic treatment of cancer but to a modest degree.