ABSTRACT
Amplification and/or overexpression of HER2 in breast cancer (BCa) patients is associated with aggressive disease and poor prognosis. Herceptin® (trastuzumab), a monoclonal antibody targeting HER2, has an established role in the treatment of HER2 positive BCa. Addition of trastuzumab to anthracycline-and taxane-based neoadjuvant treatment in women with HER2-positive BCa has resulted in improvements in pathological complete response (pCR, a strong predictor for long-term clinical outcome), event-free survival (EFS) and overall survival (OS). This study is designed to compare efficacy (pCR) and safety between the originator Herceptin and the proposed trastuzumab biosimilar EG12014. The study is conducted during the COVID-19 pandemic (last patient in: March 2020, last patient last visit: planned Jan 2022) in Belarus, Chile, Colombia, Georgia, India, Russia, South Africa, South Korea, Taiwan, and the Ukraine. Methods: Neoadjuvant phase: 807 patients were randomized (1:1) into 2 arms receiving epirubicin (90 mg/m 2) and cyclophosphamide (600 mg/m2) every 3 weeks for 4 cycles, followed by EG12014 (arm 1) or Herceptin (arm 2) (both at loading dose: 8 mg/kg and maintenance dose: 6 mg/kg) and paclitaxel (175 mg/m2) every 3 weeks Sfor 4 cycles. Subsequently, the patients underwent surgery, and primary endpoint (pCR [ypT0/is ypN0]) was assessed. Adjuvant phase: After surgery, the patients received EG12014 or Herceptin (both at loading dose: 8 mg/kg and maintenance dose: 6 mg/kg) to complete 12 months of overall trastuzumab treatment. COVID-19 infections in the study population were not expected to affect primary endpoint analysis;thus, no sensitivity analysis was performed regarding COVID-19 status (symptomatic/asymptomatic). Differences between the 2 arms regarding delays in study treatments and procedures due to COVID-19 were assessed. Results (at interim data base lock, blinded as study is ongoing): Study population: the mean age was 50 years, the majority were white Europeans with tumor stage II, estrogen receptor positive and progesterone receptor negative. The median time from date of first diagnosis was 0.5 months. Primary endpoint pCR (ypT0/is ypN0) was reached with relative risk ratio (RR) for the full analysis set: 0.992 (90% CI 0.880 to 1.118) between the 2 treatment arms. Secondary pCR endpoints (defined as ypT0 ypN0 and ypT0/is) were also reached, with RR between the treatment arms: 0.917 and 0.992, respectively. Objective clinical response prior to surgery was similar for the 2 treatment arms: 83.8% and 83.6%, respectively. EFS, OS, safety endpoints (e.g., adverse events [most frequently reported: alopecia], serious adverse events, and deaths), and toxicity assessments, supported similarity between EG12014 and Herceptin. Sixty-two patients (7.7%) were infected with COVID-19;the infections were equally distributed between the 2 treatment arms. COVID-19 did not cause any discontinuations or deaths in the study. Among all reported COVID-19 events, 13 (21%) were asymptomatic, 11 (18%) were graded as 3 (severe), and 1 (1.6%) was graded as grade 4 (life threatening). Conclusion: EG12014 has shown equivalent efficacy to Herceptin in regard to clinical response (pCR) and has also demonstrated a similar safety profile. The impact of the COVID-19 pandemic has been comparable between the two treatment arms. The influence of the pandemic on this clinical study has been relatively low considering timing and the participating countries.
ABSTRACT
Background: There are not specific information about otucomes of COVID-19 infection in patients with breast cancer. We aimed to describe the outcomes in this population in our national cohort of patients with cancer and infection for COVID-19. Methods: ACHOCC-19B registry is a multicenter observational study composed of a cross-sectional and a prospective cohort component. Eligibility criteria were the diagnosis of breast cancer and COVID-19 infection confirmed with RT-PCR. Follow-up of 30 days was completed. Clinical data were extracted of the multicentric register of cancer and covid-19 in Colombia (ACHOCC-19), collected from Apr 1 until Oct 31, 2020. The primary outcome was 30-day mortality from all causes and secondary outcome was asymptomatic disease. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using multivariable logistic regression. Results: 132 patients were included(18,5% of global ACHOCC-19 cohort). 18,2% died and 25,8% was asymptomatic. In relation to the patients who died vs did not died, 68 vs 66% were > 50 years, 20 vs 10,2% with obesity, 32 vs 51,4% without comorbidities: 24 vs 12% with Diabetes, 56 vs 29% arterial Hypertension, 17,75 vs 3.88% ECOG >2, 50 vs 12,5% progressive cancer, 20 vs 5,6% bacterial coinfection, 65 vs 25,2% received antibiotic and 68 vs 19% steroids for Covid-19 infection. 11.3% had severe infection and received ventilatory support and 66% died. About the asymptomatic patients 74% were > 50 years, 2,9% had obesity, 56% without comorbidities, 56% with ECOG 0 and 17,6% had metastatic disease. In the logistic regression analysis, age > 50 years (OR 2,7 95% 0,54-13,81), >2 comorbidities (OR 3,48 95% 0,26-45,71), progressive disease (OR 3,52 95% 0,47-26,57), steroids (OR 6,62 95% 1,5-26,6) and antibiotic treatment for Covid19 (OR 6,88 95% 1,60-29,76) behaved as a risk factors for mortality, but only steroids and antibiotic was statistically significant. Conclusions: In our study, breast cancer patients have high mortality by Covid-19 infection. Age, comorbidities, ECOG >2, progressive disease, and use of antibiotic and steroids are factors for worse prognosis. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Background: Cancer has been described as a risk factor for worse prognosis in people with Covid-19. However, there are few studies informing on the characteristics of cancer patients that have asymptomatic SARS-cov2 infection. The ACHOCC-19 study included asymptomatic patients. Methods: Analytical cohort study of patients with cancer and SARScov2 infection in Colombia. From April 1 to October 31, 2020, we collected data on demographic and clinical variables related to cancer and COVID-19 infection. We describe the characteristics and outcomes of patients who had no symptoms of COVID19. Association between outcomes and prognostic variables was analyzed using logistic regression models. Results: We included 742 patients, of which 205 (27.6%) were asymptomatic. Of these 62.2% were older than 61 years, 66% were women, 1.42% were smokers. The most frequent malignancy was breast cancer (25%), followed by colon-rectum (14.6%), sarcoma/soft tissues (5.66%) and lung cancer (5.19%). Patients were more likely to be asymptomatic if they had fewer comorbidities (0-1 comorbidities: 84% asymptomatic, 2 comorbidities: 10.85%, more than 2 comorbidities: 5.15%). 90.5% lived in urban areas and 53.37% had low income. 35.4% of patients had metastatic disease, 8.7% had progressive cancer, 40% had stable disease or partial response. No patient had an ECOG PS of 4 or more, and only 1.91% had ECOG 3. In logistic regression analysis statistically significant associations for having symptomatic disease included: man, presence of 1, 2 or > 2 comorbidities, ECOG 1,2 or 3 and cancer in progression. On the other hand, the statistically significant ORs for having asymptomatic disease were age between 18 and 30 years old, cancer in remission and receiving non-cytotoxic treatment. Table sumarizes ORs and their respective 95% CIs of the variables adjusted in the logistic regression model. Conclusions: In our stumdy, cancer patients had a higher probability of asymptomatic COVID-19 infection if they were women, between the ages of 18 and 30 years, had cancer in remission , ECOG 0 and no comorbidities. This is the first cohort of patients with cancer and asymptomatic covid 19 with a significant sample size in Latin America.