B y early March 2020, the spread of the coronavirus disease 2019 (COVID-19) outbreak had reached the Paris area, France. Since then, all medical resources have been reorganized to handle the pandemic. As a tertiary cancer center, Gustave Roussy has followed two objectives: define processes to safely sustain cancer care in a secured environment and reorganize internally to adapt its capacities to hospitalize patients with cancer and COVID-19 illness. Patients with cancer have been considered at increased risk of COVID-19, on the rationale of the increased systemic immunosuppressive state caused by the underlying malignancy and anticancer treatments. The first report from a retrospective cohort in China suggested that patients with cancer were observed to have a higher risk of severe events (for example, a composite endpoint of intensive care unit (ICU) admission, invasive ventilation or death) compared with patients without cancer (seven (39%) of 18 patients versus 124 (8%) of 1,572 patients; P = 0.0003) and that patients with cancer deteriorated more rapidly than those without cancer 1. While general determinants of COVID-19 severity have emerged from large cohorts from China and Italy 2,3 , limited data are available on the specificity of patients with cancer to help the oncology community to identify patients at risk of severe COVID-19. Furthermore, the impact of COVID-19 infection on ongoing cancer care is unexplored. This study investigated the determinants of clinical worsening and death, as well as the impact on cancer care, for the first patients sequentially managed for COVID-19 and cancer in an academic tertiary cancer center. Results Patient population. From 24 March 2020 until 29 April 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in 196 (12%) of 1,633 tests performed internally at the Gustave Roussy Cancer Centre. Overall, 209 patients were identified (including a few identified by PCR with reverse transcription (RT-PCR) performed at another facility and some diagnosed by computed tomography scan alone) and the final study population included 178 adult patients. The following were reasons for exclusion: pediatric population (six patients); non-cancer patients (19 patients); and COVID-19 ultimately ruled out (six patients). Baseline demographics, comorbidities and underlying cancer characteristics for

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Background: Intrahepatic cholangiocarcinoma (iCCA) is a subset of cholangiocarcinoma. Poor prognosis and limited treatment options are the major clinical challenges for iCCA patients. Fibroblast growth factor receptor 2 (FGFR2) has emerged as a tumorigenic driver gene in iCCA and pemigatinib had approved for the target treatment of FGFR2 fusion/rearrangement. Methods: Deep sequencing targeting 450 cancer genes was performed in a laboratory accredited by College of American Pathologists (CAP) and certified by Clinical Laboratory Improvement Amendments (CLIA) for genomic alteration identification. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Statistical analysis was performed by Fisher's exact test.Results: A total of 92 Chinese resectable iCCA patients, including 35 females and 57 males, were enrolled in this study. The most commonly altered genes included TP53 (36%, 33/92), KRAS (27%, 25/92), ARID1A (18%, 17/92), CDKN2A (15%, 14/92), TERT (14%, 13/92), PBRM1 and BAP1 (13%, 12/92, for both), FGFR2 (12%, 11/92) and BRAF (11%, 11/92). Nine (9.8%) iCCA patients harbored FGFR2 fusion. Consistent with previous reports, patients with FGFR2 fusion tend to occur more commonly in females (17% vs 5%, P¼0.08). The average TMB value of patients with FGFR2 fusion was 2.0 muts/Mb (ranged 0.6-4.3 muts/Mb), and 6 muts/Mb (ranged 0-45.2 muts/Mb) in patients without FGFR2 fusion. There was no difference in TMB between patients with or without FGFR2 fusion (P¼0.35). In FGFR2 fusion patients, the most frequent mutated genes were BAP1 (33%, 3/9) and PIK3CA (33%, 3/9). Interestingly, Co-mutation analysis showed that FGFR2 fusion were significantly associated with the mutation of PIK3CA (P < 0.01), but mutually exclusive with the mutation of KRAS (P < 0.015) in iCCA. There was no significant difference in disease free survival (DFS) between patients with FGFR2 fusion or not (P¼0.86). Conclusions:The identification of FGFR2 fusion indicated that 9.8% Chinese iCCA patients had the opportunity to benefit from FGFR2 fusion targeting drugs. DFS analysis of FGFR2 fusion patients shows that the molecular mechanism of Chinese patients with iCCA is different from that of western countries. However, further study with expansion cohort is still needed.

Therapeutic options in patients with metastatic osteosarcoma are limited and effective systemic treatments are needed in this setting. The aim of this case series was to assess the efficacy and toxicity of oral metronomic etoposide in adult patients with progressive metastatic osteosarcoma. We retrospectively reviewed the electronic records of patients treated with oral metronomic etoposide (25 mg thrice daily, 3 weeks out of 4) from December 2002 to December 2018 at Gustave Roussy (Villejuif, France). The primary endpoint was progression‐free rate (PFR) at 4 months; secondary endpoints were: best response (according to RECIST v1.1), progression‐free survival (PFS), overall survival (OS) and safety. With a median follow‐up of 9.8 months, 37 patients were eligible for this analysis: 68% males, median age 42 (range: 21–75), 19% with synchronous metastases, 92% with lung metastases, median PS: 1 (range: 0–3). Median number of previous treatment lines in the metastatic setting was 1 (range: 0–4). Progression‐free rate at 4 months was 40.3% (95% CI: 24.5–56.2). Best response was partial response in 11% and stable disease in 35% of patients (disease control rate: 46%). Median PFS was 3.1 months (95% CI: 2.5–4.7) and median OS was 9.8 months (95% CI: 5.1–12.3). Toxicity profile was acceptable, with 13% grade 3 haematological toxicities (anaemia and neutropenia), without any grade 3–4 non‐haematological toxicity. In our experience, oral metronomic etoposide demonstrated effective palliation along with acceptable toxicity in patients with progressive metastatic osteosarcoma.

Background: Chemotherapy combined with either VEGF or EGFR targeting mAbs improves survival of patients (pts) with mCRC. In clinical practice, the selection of antibody may take into account multiple factors, including RAS/BRAF mutation status and tumour sidedness. Methods: IPD from 2 randomized first-line trials with head-to-head comparison of chemo+EGFRmAb v chemo+VEGFmAb in mCRC were pooled. Biomarker subpopulations (see table) were analysed. Overall survival (OS) and progression-free survival (PFS) were compared between groups by Cox model, stratified by studies and adjusted by age, gender and performance status. Treatment effects were estimated by adjusted hazard ratio (HR adj) and 95% confidence interval (CI). Within each biomarker subset, mAb efficacy was explored according to type of chemo, gender, sidedness and site of metastasis. Interaction tests were performed. P-values < 0.01 were considered statistically significant to account for multiple comparisons.

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