One-month Humoral Response Following Two Doses of Covid-19 Vaccines in Specific populations - ANRS0001S COV POPART Cohort Study

Background. We evaluated the immune response to COVID-19 vaccines in several specific populations at high risk of severe COVID-19. Methods. Participants from the French national multi-center prospective cohort studyANRS0001S COV-POPART were included (11 specific subpopulations: and 2 control groups (18-64 years and over 65 years)). In this preliminary analysis patients and controls who had received at least two vaccine doses have been included. Percentages (95% confidence intervals (CI)) of participants with anti-Spike SARS-CoV-2 IgG antibodies (ELISA) and specific neutralizing antibodies (in vitro neutralization assay) were evaluated at one month after the second dose of COVID-19 vaccine. Results. 3703 were included: 2650 participants from specific subpopulations (171 solid cancers, 160 SOT, 100 HCT, 91 chronic renal failures, 141 systemic autoimmune diseases, 157 autoimmune inflammatory rheumatic diseases, 361 multiple sclerosis (MS) or neuromyelitis optica spectrum disorders, 61 hypogammaglobulinemia, 401 diabetic, 739 obeses non-diabetic and 476 HIV) and 1053 controls (893: 18- 64 years and 160 over 65 years). Median age was 51.7 years [InterQuartile range: 40.8 - 60.9] and 50.7% were male. Most of the participants received BNT162b2 vaccine (86.4%). In the control group, 100% (95%CI: 99.6;100.0) of those aged 18-64 and 99.4% (96.6;100.0) of those over 65 years developed anti-Spike IgG antibodies. PLWHIV, cancer and diabetic patients had high rate of responders after two doses with 98.3% (97.2;99.1), 93.0% (88.1;96.3) and 92.0% (88.9;94.5), respectively. The lowest percentage of responders was found in patients with SOT (13.8% (8.8;20.1), HSCT (34.0% (24.8;44.2) and hypogammaglobulinemia (52.5% 39.3;65.4). In both control groups, the frequency of neutralizing antibodies was similar to the anti-Spike IgG antibody response. In the immunodeficient populations, neutralizing antibodies responders tended to be less frequent than anti-Spike antibodies responders. Similar trends than for IgG antibody were identified (Figure 1). Anti-Spike and Neutralizing antibody (Ab) responses (95% CI) one month after the second dose of COVID-19 vaccine in specific and control populations. Conclusion. Lower COVID-19 vaccine humoral response was observed in specific populations than in controls, especially in patients with hypogammaglobulinemia, HSCT and SOT. (Figure Presented).

REGISTRI: Regorafenib in first-line of KIT/PDGFR wild type advanced GIST: Capatalize the A Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial

Background: Around 15% of adult GIST are wild type for KIT/PDGFRA mutations (KPWT), usually have SDH deficiencies, and are resistant to imatinib (IM). The underlying mechanisms include overexpression of HIF1α in SDH deficient-GIST, high IGFR signaling through MAPK, BRAF mutation or STAT3 activation. Regorafenib (RE), targeting these pathways, could be more active as upfront therapy in KPWT GIST. Methods: Patients (pts) >18, with advanced non pretreated KPWT GIST were eligible after central confirmation by next-generation sequencing (NGS). Eligible pts received RE at 160mg/d for 21/28d cycles. Primary end-point was disease control rate (DCR) at 12 weeks (RECIST 1.1 ) by central radiological assessment (CRA). Secondary objectives were PFS, OS, ORR (RECIST,Choi), safety and QoL. An amendment allowed previous IM (adjuvant). Statistical assumptions [H0 73% and H1 90% (α 0.1 and β 0.2)], defined a sample size of 20 pts. Results: From May 2016 to October 2020, 30pts with KPWT GIST (by Sanger) underwent central molecular screening. Among the 15 non-eligible pts, 8 harbored KIT exon 11 mutations, 3 exon 9 and 3 PDGFRA exon 18 by NGS. The remaining 16 (53.3%) molecularly eligible pts were enrolled and started RE except one pt due to COVID-19 pandemic. The trial was prematurely closed due to low recruitment, especially after COVID outbreak. Demographics and treatment details in the table. Based on CRA, 12w-DCR was 86.7%. With a median (m) FU of 26 (5-44) months (mo), 10/15 pts progressed, with a mPFS of 10.8 mo (95% CI 6.9-14.8). 6 mo, 9 mo and 12 mo PFS rates were 65%, 48% and 29% respectively. 2 pts were PD-free at 25 and 43 mo from start of RE. 6/15 pts died, with a mOS of 33.5 mo (95% CI NR). [Formula presented] Conclusions: The study results approach the prespecified activity threshold. The low recruitment rate could have affected this attainment. Other analysis of secondary endpoints are ongoing. The high percentage of overlooked mutant GIST by Sanger raises the need of NGS in presumed KPWT GIST. Clinical trial identification: NCT02638766. Legal entity responsible for the study: Spanish Group for Research on Sarcoma (GEIS). Funding: Bayer. Disclosure: J. Martin Broto: Financial Interests, Personal, Expert Testimony, Honoraria: Lilly;Financial Interests, Personal, Expert Testimony, Honoraria: PharmaMar;Financial Interests, Personal, Expert Testimony, Honoraria: Eisai;Financial Interests, Personal, Expert Testimony, Honoraria: Bayer;Financial Interests, Personal, Invited Speaker: PharmaMar;Financial Interests, Institutional, Invited Speaker: PharmaMar;Financial Interests, Institutional, Invited Speaker: Eisai;Financial Interests, Institutional, Invited Speaker: Novartis;Financial Interests, Institutional, Invited Speaker: IMMIX Biopharma;Financial Interests, Institutional, Invited Speaker: Lixte;Financial Interests, Institutional, Invited Speaker: Karyopharm;Financial Interests, Institutional, Invited Speaker: Bayer;Financial Interests, Institutional, Invited Speaker: Celgene;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker: BMS;Financial Interests, Institutional, Invited Speaker: Blueprint;Financial Interests, Institutional, Invited Speaker: Deciphera;Financial Interests, Institutional, Invited Speaker: Nektar;Financial Interests, Institutional, Invited Speaker: FORMA;Financial Interests, Institutional, Invited Speaker: Amgen;Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo;Financial Interests, Institutional, Invited Speaker: Lilly;Financial Interests, Institutional, Invited Speaker: AROG;Financial Interests, Institutional, Invited Speaker: Adaptimmune;Financial Interests, Institutional, Invited Speaker: GSK. N. Hindi: Financial Interests, Personal, Invited Speaker: PharmaMar;Financial Interests, Personal, Advisory Board: PharmaMar;Financial Interests, Institutional, Research Grant: PharmaMar;Financial Interests, Institutional, Sponsor/Funding: PharmaMar;Financial Interests, Institutional, Research Grant: Nova tis;Financial Interests, Institutional, Research Grant: Eisai;Financial Interests, Institutional, Research Grant: Immix Bio;Financial Interests, Institutional, Sponsor/Funding: Bayer;Financial Interests, Institutional, Sponsor/Funding: Deciphera;Financial Interests, Institutional, Sponsor/Funding: Daychii;Financial Interests, Institutional, Sponsor/Funding: Blueprint;Financial Interests, Institutional, Sponsor/Funding: Adaptimmune;Financial Interests, Institutional, Sponsor/Funding: GSK;Financial Interests, Institutional, Sponsor/Funding: Karyopharm;Financial Interests, Institutional, Sponsor/Funding: Celgene;Financial Interests, Institutional, Sponsor/Funding: AROG. J. Lavernia: Financial Interests, Personal, Invited Speaker: PharmaMar;Financial Interests, Personal, Invited Speaker: BMS. C. Serrano: Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Institutional, Research Grant: Bayer. D. Moura: Financial Interests, Institutional, Research Grant: Novartis;Financial Interests, Institutional, Research Grant: Eisai;Financial Interests, Institutional, Research Grant: PharmaMar;Financial Interests, Institutional, Research Grant: Immix Bio. J. Blay: Financial Interests, Institutional, Research Grant: Bayer;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Institutional, Research Grant: Novartis;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Institutional, Research Grant: Roche;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Institutional, Research Grant: Deciphera;Financial Interests, Personal, Research Grant: Deciphera. E.R. Fumagalli: Financial Interests, Institutional, Research Grant: Bayer. All other authors have declared no conflicts of interest.

Delayed care for patients with newly diagnosed cancer due to COVID-19 and estimated impact on cancer mortality in France.

BACKGROUND: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. PATIENTS AND METHODS: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. RESULTS: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. CONCLUSIONS: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years.