Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. NCT04354701

Purpose: This trial was conducted to determine the maximum tolerated dose (MTD) and preliminary efficacy of buparlisib, an oral pan-class I PI3K inhibitor, plus fulvestrant in postmenopausal women with metastatic estrogen receptor positive (ER⁺) breast cancer. Experimental Design: Phase IA employed a 3+3 design to determine the MTD of buparlisib daily plus fulvestrant. Subsequent cohorts (phase IB and cohort C) evaluated intermittent (5/7-day) and continuous dosing of buparlisib (100 mg daily). No more than 3 prior systemic treatments in the metastatic setting were allowed in these subsequent cohorts. Results: Thirty-one patients were enrolled. MTD was defined as buparlisib 100 mg daily plus fulvestrant. Common adverse events (AE) included fatigue (38.7%), transaminases elevation (35.5%), rash (29%), and diarrhea (19.4%). C-peptide was significantly increased during treatment, consistent with on-target effect of buparlisib. Compared with intermittent dosing, daily buparlisib was associated with more frequent early onset AEs and higher buparlisib plasma concentrations. Among the 29 evaluable patients, the clinical benefit rate was 58.6% (95% CI, 40.7%–74.5%). Response was not associated with PIK3CA mutation or treatment cohort; however, loss of PTEN, progesterone receptor (PgR) expression, or mutation in TP53 was most common in resistant cases, and mutations in AKT1 and ESR1 did not exclude treatment response. Conclusions: Buparlisib plus fulvestrant is clinically active with manageable AEs in patients with metastatic ER⁺ breast cancer. Weekend breaks in buparlisib dosing reduced toxicity. Patients with PgR negative and TP53 mutation did poorly, suggesting buparlisib plus fulvestrant may not be adequately effective against tumors with these poor prognostic molecular features. Clin Cancer Res; 22(7); 1583–91. ©2015 AACR.

The mainstay treatment for unresectable or metastatic melanoma is systemic therapy. Before the introduction of immune checkpoint inhibitors (ICIs), the standard of care for most patients with metastatic melanoma was dacarbazine administered as single-agent therapy or part of combination therapy.^1,2 Immunotherapy with high-dose interleukin 2 showed durable response in a few patients but was associated with significant toxic effects^2,3; however, immunotherapeutic agents in the form of ICIs, including ipilimumab, nivolumab, and pembrolizumab, have substantially improved outcomes and become the standard of care for metastatic melanoma during the past decade.⁴

Nivolumab is an immune checkpoint inhibitor targeting programmed death-1 protein and has been approved for the treatment of multiple advanced malignancies. Adverse effects of immune checkpoint inhibitors are distinct from conventional cytotoxic chemotherapy and can be life-threatening if left unrecognized. Here, we present a case of nivolumab-induced pericardial effusion successfully managed with high-dose corticosteroids. A 70-year-old Caucasian female with a history of 50-pack-year cigarette smoking was diagnosed of recurrent adenocarcinoma of lung after initial surgery. She progressed through multiple lines of chemotherapy and was eventually started on nivolumab. She developed a large pericardial effusion, grade 3 by Common Terminology Criteria for Adverse Events v4.0, about 4 days after receiving first nivolumab treatment. She was treated with oral prednisone at 1 mg/kg daily with gradual resolution of pericardial effusion over 5 weeks while she still received nivolumab every 2 weeks. Prednisone treatment was eventually tapered off about 10 weeks from initial nivolumab treatment. However 1 week after stopping prednisone, she again presented with shortness of breath and bilateral ankle edema, imaging confirmed recurrent pericardial effusion measuring 2.8 cm. Nivolumab was stopped and patient was again started back on prednisone 1 mg/kg daily which resulted in complete resolution of pericardial effusion in 3 weeks. Nivolumab was resumed 1 week afterwards while patient was on tapering dose of prednisone. There was no recurrent pericardial effusion when she continued low-dose prednisone during the remaining course of nivolumab treatment. With increasing use of immune checkpoint inhibitors, clinicians need to be aware of the unusual immune-related adverse events in order to provide timely management and effective patient care. To our knowledge, this is the first reported case of immune-related pericardial effusion from nivolumab successfully managed with high-dose corticosteroids. Furthermore, recurrent pericardial effusion was prevented by using low-dose corticosteroids as maintenance in order for patient to continue nivolumab treatment.