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BACKGROUND: Solid cancer is an independent prognostic factor for poor outcome with COVID-19. As guidelines for patient management in that setting depend on retrospective efforts, we here present the first analyses of a nationwide database of patients with cancer hospitalized with COVID-19 in Belgium, with a focus on changes in anticancer treatment plans at the time of SARS-CoV-2 infection. METHODS: Nineteen Belgian hospitals identified all patients with a history of solid cancer hospitalized with COVID-19 between March 2020 and February 2021. Demographic, cancer-specific and COVID-specific data were pseudonymously entered into a central Belgian Society of Medical Oncology (BSMO)-COVID database. The association between survival and primary cancer type was analyzed through multivariate multinomial logistic regression. Group comparisons for categorical variables were carried out through a Chi-square test. RESULTS: A total of 928 patients were registered in the database; most of them were aged ≥70 years (61.0%) and with poor performance scores [57.2% Eastern Cooperative Oncology Group (ECOG) ≥2]. Thirty-day COVID-related mortality was 19.8%. In multivariate analysis, a trend was seen for higher mortality in patients with lung cancer (27.6% versus 20.8%, P = 0.062) and lower mortality for patients with breast cancer (13.0% versus 23.3%, P = 0.052) compared with other tumour types. Non-curative treatment was associated with higher 30-day COVID-related mortality rates compared with curative or no active treatment (25.8% versus 14.3% versus 21.9%, respectively, P < 0.001). In 33% of patients under active treatment, the therapeutic plan was changed due to COVID-19 diagnosis, most frequently involving delays/interruptions in systemic treatments (18.6%). Thirty-day COVID-related mortality was not significantly different between patients with and without treatment modifications (21.4% versus 20.5%). CONCLUSION: Interruption in anticancer treatments at the time of SARS-CoV-2 infection was not associated with a reduction in COVID-related mortality in our cohort of patients with solid cancer, highlighting that treatment continuation should be strived for, especially in the curative setting. ispartof: ESMO OPEN vol:7 issue:6 ispartof: location:England status: published

Background: This phase II study assessed the safety and efficacy of everolimus, an oral mammalian target of rapamycin inhibitor in advanced transitional carcinoma cell (TCC) after failure of platinum-based therapy. Patients and methods: Thirty-seven patients with advanced TCC received everolimus 10 mg/day until progressive disease (PD) or unacceptable toxicity. The primary end point was the disease control rate (DCR), defined as either stable disease (SD), partial response (PR), or complete response at 8 weeks. Angiogenesis-related proteins were detected in plasma and changes during everolimus treatment were analyzed. PTEN expression and PIK3CA mutations were correlated to disease control. Results: Two confirmed PR and eight SD were observed, resulting in a DCR of 27% at 8 weeks. Everolimus was well tolerated. Compared with patients with noncontrolled disease, we observed in patients with controlled disease a significant higher baseline level of angiopoietin-1 and a significant early plasma decrease in angiopoietin-1, endoglin,and platelet-derived growth factor-AB. PTEN loss was observed only in patients with PD. Conclusions: Everolimus showed clinical activity in advanced TCC. The profile of the plasma angiogenesis-related proteins suggested a role of the everolimus antiangiogenic properties in disease control. PTEN loss might be associated with everolimus resistance.

Epidermal growth factor receptor tyrosine kinase inhibitors represent a new treatment option for patients with advanced nonsmall cell lung cancer (NSCLC). This retrospective study examined to what extent previous clinical trial experience matches large-scale Western community implementation of this treatment. In the Belgian expanded access programme, the data from 513 patients with advanced or metastatic NSCLC, not suitable for further chemotherapy and receiving oral gefitinib 250 mg.day(-1) until disease progression, death or unacceptable toxicity, were analysed. The median (range) duration of gefitinib treatment was 2.3 months (0.0-32.7). Its use was predominantly in second- or third-line treatment. The overall response and disease control rates were 8.9 and 41.2%, respectively. In univariate analysis, response was more common in females and never-smokers. In multivariate analysis, female sex was the only significant predictive factor (odds ratio (OR) (95% confidence interval (CI)) 0.329 (0.129-0.839)). Symptom improvement was reported in 108 patients of whom 32 (29.6%) had an objective response, 66 (61.1%) experienced disease stabilisation and 10 (9.3%) progressed. Gefitinib was well tolerated; only 7.8% of the patients reported grade 3 or 4 toxicity. The overall median survival was 4.7 months, with a 1-yr survival rate of 21%. Survival was strongly influenced by a better performance status (PS) (good PS: hazard ratio (HR) (95%CI) 0.110 (0.077-0.157)) and adenocarcinoma with bronchioloalveolar carcinoma features histology (HR (95%CI) 0.483 (0.279-0.834)). In conclusion, the activity of gefitinib was confirmed in the present large Western community implementation study. Response, present in a small subgroup, led to a rewarding survival and could be predicted by sex only. Baseline performance status and adenocarcinoma with bronchioloalveolar carcinoma features histology were significant factors for survival.

Background: The epidermal growth factor receptor (EGFR) plays a role in triple-negative (estrogen receptor-, progesterone receptor-, HER2-negative) breast cancer (TNBC). This randomized, phase II study investigated the combination of the EGFR monoclonal antibody cetuximab and cisplatin in the treatment of metastatic (m) TNBC. Methods: Patients (pts) with mTNBC who had received ≥1 prior chemotherapy regimen for metastatic disease, were randomized 2:1 to treatment with either: cetuximab (400 mg/m2 initial dose then 250 mg/m2 weekly) + ≥6x 3-weekly cycles of cisplatin (75 mg/m2, d1); or ≥6x 3-weekly cycles of cisplatin alone. In the cisplatin arm, pts with disease progression (PD) during the 6 cisplatin cycles could switch to cetuximab plus cisplatin and those with PD after the 6 cycles could receive cetuximab alone. The primary endpoint was best overall response. Simultaneous null hypotheses assumed that the overall response rate (ORR) in the combination arm was ≥20% and that the ORRs were equal in both arms. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. All statistical tests were performed at alpha-level 0.1 Results: 173 pts were included in the intention-to-treat population: 115 were randomized to cetuximab/cisplatin and 58 to cisplatin. The cetuximab/cisplatin and cisplatin arms were well balanced for patient and disease characteristics (randomization strata, 73% first and 27% second line in both arms). Differences included: age ≥65 years (19.1% vs 12.1%) and lung metastases (55.7% vs 44.8%). 30 pts receiving cisplatin alone switched to cetuximab/cisplatin after first PD. 79.6% of patients on cetuximab/cisplatin and 73.7% on cisplatin received ≥90% of the relative dose intensity of cisplatin. Adverse events (AEs) were manageable and in line with what was expected from the different agents (grade 3/4 AEs are shown in the Table). Grade 3/4 AEs (%) Adding cetuximab to cisplatin nearly doubled the ORR: 20.0% (95% CI 13.1%, 28.5%) vs 10.3% (95% CI 3.9%, 21.2%) (p=0.5 for testing ORR against 20.0%), with an odds ratio of 2.126 (90% CI 0.945, 4.786, p=0.11). Cetuximab/cisplatin was associated with a significant 32.5% reduction in the risk of disease progression compared with cisplatin alone HR 0.675 (95% CI 0.470, 0.969, p=0.032). Median PFS times were 3.7 and 1.5 months, respectively. The benefits of cetuximab/cisplatin over cisplatin on ORR and PFS were observed consistently across sub-groups (according to patient, disease and treatment characteristics), but sample sizes were small. OS results will be presented at the meeting. Conclusions: Adding cetuximab to cisplatin increased the ORR compared with cisplatin alone and significantly improved PFS in mTNBC. Safety was manageable. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD01-01.