COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study.

BACKGROUND: Individuals with cancer, particularly those who are receiving systemic anticancer treatments, have been postulated to be at increased risk of mortality from COVID-19. This conjecture has considerable effect on the treatment of patients with cancer and data from large, multicentre studies to support this assumption are scarce because of the contingencies of the pandemic. We aimed to describe the clinical and demographic characteristics and COVID-19 outcomes in patients with cancer. METHODS: In this prospective observational study, all patients with active cancer and presenting to our network of cancer centres were eligible for enrolment into the UK Coronavirus Cancer Monitoring Project (UKCCMP). The UKCCMP is the first COVID-19 clinical registry that enables near real-time reports to frontline doctors about the effects of COVID-19 on patients with cancer. Eligible patients tested positive for severe acute respiratory syndrome coronavirus 2 on RT-PCR assay from a nose or throat swab. We excluded patients with a radiological or clinical diagnosis of COVID-19, without a positive RT-PCR test. The primary endpoint was all-cause mortality, or discharge from hospital, as assessed by the reporting sites during the patient hospital admission. FINDINGS: From March 18, to April 26, 2020, we analysed 800 patients with a diagnosis of cancer and symptomatic COVID-19. 412 (52%) patients had a mild COVID-19 disease course. 226 (28%) patients died and risk of death was significantly associated with advancing patient age (odds ratio 9·42 [95% CI 6·56-10·02]; p<0·0001), being male (1·67 [1·19-2·34]; p=0·003), and the presence of other comorbidities such as hypertension (1·95 [1·36-2·80]; p<0·001) and cardiovascular disease (2·32 [1·47-3·64]). 281 (35%) patients had received cytotoxic chemotherapy within 4 weeks before testing positive for COVID-19. After adjusting for age, gender, and comorbidities, chemotherapy in the past 4 weeks had no significant effect on mortality from COVID-19 disease, when compared with patients with cancer who had not received recent chemotherapy (1·18 [0·81-1·72]; p=0·380). We found no significant effect on mortality for patients with immunotherapy, hormonal therapy, targeted therapy, radiotherapy use within the past 4 weeks. INTERPRETATION: Mortality from COVID-19 in cancer patients appears to be principally driven by age, gender, and comorbidities. We are not able to identify evidence that cancer patients on cytotoxic chemotherapy or other anticancer treatment are at an increased risk of mortality from COVID-19 disease compared with those not on active treatment. FUNDING: University of Birmingham, University of Oxford.

T-DM1 in the Neo-Adjuvant Treatment of HER2-Positive Breast Cancer: Impact of the KRISTINE (TRIO-021) Trial.

BACKGROUND: Neo-adjuvant chemotherapy (NAC) can facilitate breast conservation, allows in vivo testing of chemotherapy sensitivity and provides a route to accelerated approval of new therapies. For HER2 positive breast cancer, the anti-HER2 monoclonal antibody, trastuzumab, is a standard component of neo-adjuvant therapy. Pertuzumab is an anti-HER2 monoclonal antibody with a distinct binding site to trastuzumab, which prevents HER2 receptor dimerisation. In early breast cancer, the addition of pertuzumab to docetaxel and trastuzumab resulted in a higher rate of pathological complete response (pCR), leading to accelerated approval in many territories. T-DM1 is a novel antibody-drug conjugate, combining trastuzumab with a potent cytotoxic, DM1, a maytansine derivative, via a stable thioether linker. In advanced breast cancer (ABC), T-DM1 improves survival compared to standard 2nd or 3rd line regimens, but not compared to first line chemotherapy plus trastuzumab. The KRISTINE trial investigated the combination of T-DM1 with pertuzumab compared to standard chemotherapy plus trastuzumab and pertuzumab in early breast cancer. METHODS: This review summarises the data supporting current standards in the neo-adjuvant treatment of HER2 positive early breast cancer and the impact of the KRISTINE trial results. RESULTS: T-DM1 with pertuzumab did not improve pCR over standard therapy, although the novel combination was better tolerated, and a sub-group of patients (44%) achieved pCR with the systemic chemotherapy-free regimen. This suggests that not all HER2 positive early breast cancer patients require systemic chemotherapy and provides the potential, if these patients can be identified up-front, to de-escalate therapy. CONCLUSION: Although the KRISTINE trial results have not changed the standard of care for the neoadjuvant management of HER2 positive breast cancer, further research is needed to determine whether T-DM1 could be used to de-escalate NAC for selected patients.