Cancer patients are presumed to be at increased risk from COVID-19 infection fatality due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. A total of 218 COVID-19 positive patients from March 18th-April 8th, 2020 with a malignant diagnosis were identified. A total of 61 (28%) cancer patients died from COVID-19 with a case fatality rate (CFR) of 37% (20/54) for hematologic malignancies and 25% (41/164) for solid malignancies. 6/11 (55%) lung cancer patients died from COVID-19 disease. Increased mortality was significantly associated with older age, multiple comorbidities, need for ICU support, and elevated levels of D-Dimers, LDH and lactate on multivariable analysis. Ageadjusted CFRs in cancer patients compared to non-cancer patients at our institution and NYC reported a significant increase in case fatality for cancer patients. These data suggest the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population.Research.on June 9, 2020.

Highlights d COVID-19 vaccines lead to high rates of seroconversion among patients with cancer d Patients with hematologic malignancies show lower immunogenicity post vaccination d Prior immunosuppressive therapies lead to lower responsiveness to COVID-19 vaccines d Prior COVID infection leads to more robust antibody responses to COVID-19 vaccines

Cetuximab is a monoclonal antibody that targets the human epidermal growth factor receptor (EGFR). Although approved for use in EGFR-overexpressing advanced colorectal cancer, recent studies have shown a lack of association between EGFR overexpression and cetuximab response, requiring the identification of novel biomarkers predictive of response to this agent. To do so, 22 colon cancer cell lines were screened for cetuximab response in vitro and sensitive and resistant lines were identified. In sensitive cell lines, cetuximab induced a G 0 -G 1 arrest without inducing apoptosis. Notably, cetuximabsensitive but not cetuximab-resistant cell lines were preferentially responsive to EGF-stimulated growth. Whereas neither EGFR protein/mRNA expression nor gene copy number correlated with cetuximab response, examination of the mutation status of signaling components downstream of EGFR showed that cell lines with activating PIK3CA mutations or loss of PTEN expression (PTEN null) were more resistant to cetuximab than PIK3CA wild type (WT)/PTENexpressing cell lines (14 F 5.0% versus 38.5 F 6.4% growth inhibition, mean F SE; P = 0.008). Consistently, PIK3CA mutant isogenic HCT116 cells showed increased resistance to cetuximab compared with PIK3CA WT controls. Furthermore, cell lines that were PIK3CA mutant/PTEN null and Ras/BRAF mutant were highly resistant to cetuximab compared with those without dual mutations/PTEN loss (10.8 F 4.3% versus 38.8 F 5.9% growth inhibition, respectively; P = 0.002), indicating that constitutive and simultaneous activation of the Ras and PIK3CA pathways confers maximal resistance to this agent. A priori screening of colon tumors for PTEN expression status and PIK3CA and Ras/BRAF mutation status could help stratify patients likely to benefit from this therapy.