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Immune checkpoint inhibitors yielded unprecedented outcomes in patients with mismatch repair deficient/ microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC), but clinical decision-making in this rapidly evolving treatment landscape is challenging. Since performance status (PS) represents a well-established prognostic factor in clinical practice, we investigated whether worse PS, overall or related to either patients' frailty or high tumour burden, could affect the outcomes in this whole patients' population and according to immune checkpoint inhibitor treatment type.We conducted a global study at Tertiary Cancer Centres and collected data of patients with dMMR/MSI-H mCRC treated with anti- programmed-death (ligand)-1 (PD(L)-1) monotherapy or anti-PD-1/anti- cytotoxic T-lymphocyte antigen 4 combination.The cohort included 502 patients. At a median follow-up of 31.2 months, worse PFS and OS were reported in patients with patient-related PS ≥ 1 (adjusted-HRs: 1.73, 95%CI: 1.06-2.83, p = 0.004 and 2.06, 95%CI: 1.13-3.74, p = 0.001, respectively) and cancer-related PS ≥ 1 (adjusted-HRs: 1.61, 95%CI: 1.19-2.17, p = 0.004 and 1.87, 95%CI: 1.32-2.66, p = 0.001, respectively). Anti-PD-1/anti- cytotoxic T-lymphocyte antigen 4 combination did not provide significantly better survival compared to anti-PD(L)-1 monotherapy in PS 0 subgroup (PFS HR = 0.62, 95%CI: 0.37-1.02, p = 0.059; OS HR = 0.59, 95%CI: 0.32-1.11, p = 0.100) and in patient-related PS ≥ 1 (PFS HR 0.93, 95%CI: 0.31-2.83, p = 0.899; OS HR 1.22, 95%CI: 0.34-4.37, p = 0.760), but the difference was significant and clinically meaningful in the subgroup with cancer-related PS ≥ 1 (PFS HR = 0.32, 95%CI: 0.19-0.53, p lt; 0.001; OS HR = 0.26, 95%CI: 0.14-0.48, p lt; 0.001).In patients with dMMR/MSI-H mCRC, an extensive evaluation of clinical variables including PS may be implemented in the therapy decision-making.

Background: The novel COVID-19 outbreak spread rapidly around the world Cancer patients (pts) consist of a highly vulnerable group due to underlying malignancy and/or treatment-induced immunosuppression A high mortality rate from COVID-19 in cancer pts was previously reported France is the fourth most affected country, with more than 150,000 infected individuals and over 28,000 deaths GCO-002 CACOVID-19 study is a large French nationwide cohort of COVID-19 pts with solid tumors with the aim to identify risk factors of COVID-19 severity and evaluate impact on cancer treatment Methods: Bispective multicenter cohort set up by the French Cooperative Groups in solid cancers: ANOCEF-IGCNO (CNS tumors), ARCAGY-GINECO (gynecological and breast cancers), FFCD (digestive cancers), GERCOR (digestive and other solid cancers), GORTEC/intergroupe ORL (head and neck cancers (HNAmgen, Pierre Fabre;Sandoz;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer;Novartis;Honoraria (self): Celgene;HalioDx;Lilly;Honoraria (self), Travel/Accommodation/Expenses: BMS;Roche;Honoraria (self), Research grant/Funding (self): Incyte;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen;Merck;Servier;Research grant/Funding (self): Integragen;Travel/Accommodation/Expenses: AAA;Pfizer A Turpin: Honoraria (self): Servier;Advisory/Consultancy: Mylan;Merck Serono;Amgen;Travel/Accommodation/Expenses: Merck;Sanofi;Pfizer;AstraZeneca I L Ray-Coquard: Honoraria (self), Advisory/Consultancy: Abbvie;Agenus;Advaxis;Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS;MSD;Honoraria (self), Advisory/Consultancy: PharmaMar;Genmab;Pfizer;Deciphera;Mersena;Amgen;Tesaro;Clovis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Serono;Novartis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK;Non-remunerated activity/ies: GINECO;ENGOT;GCIG;European community;ESMO;ASCO;ESGO;IGSC;Inca;Swiss and German Health Authorities;Italian Health Authority;Belgium Health Authority J Thariat: Honoraria (self): BMS;Honoraria (institution), Travel/Accommodation/Expenses, Full/Part-time employment: Centre Francois Baclesse;Leadership role: President of the French Head and Neck Intergroup, GORTEC secretary;Non-remunerated activity/ies: Director of Easy-CRF society;Research grant/Funding (institution): Nanobiotix G Ahle: Travel/Accommodation/Expenses: Abbvie;Biogen;Novartis;Roche;Sanofi;Non-remunerated activity/ies: ANOCEF;NENO;AlSacEP R Mathieu: Honoraria (self), Research grant/Funding (self): Astellas;Honoraria (self): AstraZeneca;Ferring;Ipsen;Janssen;MSD;Pfizer;Sanofi;Takeda D Debieuvre: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Roche;Novartis;BMS;MSD;Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (self), Research grant/Funding (institution): Chugai;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boerhinger-Ingelheim;Research grant/Funding (institution): Chiesi;Sandoz;Takeda;GSK;Research grant/Funding (self): Lilly A Canellas: Honoraria (self), Advisory/Consultancy: BMS;Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca;Travel/Accommodation/Expenses: Oxyvie;LVL Medical;Boerhinger Ingelheim A-C Hardy-Bessard: Advisory/Consultancy: Clovis;Novartis;Roche;MSD;AstraZeneca;GSK L Mansi: Honoraria (institution), Advisory/Consultancy: Sandoz;Advisory/Consultancy: Roche;Eisai;Pfizer;Novartis;Speaker Bureau/Expert testimony: Exact Sciences;Travel/Accommodation/Expenses: Lilly P Gorphe: Honoraria (self): Intuitive Surgical;Non-remunerated activity/ies: Chair, scientific board, French Head and Neck Intergroup;Research grant/Funding (institution): MSD A IDBAIH Ahmed: Research grant/Funding (institution): Transgene;Sanofi;Air Liquide;Travel/Accommodation/Expenses: Carthera;Leo Pharma G Zalcman: Honoraria (self), Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (institution): Takeda;Travel/Accommodation/Expenses: Pfizer;AbbVie;MSD O Bouche: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy: Merck KgaA;Bayer;AstraZeneca;Grunenthal;MSD;Honoraria (self), Speaker Bureau/Expert testimony: Amgen;Pierre Fabre;Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Servier All other authors have declared no conflicts of interest

Microsatellite instability (MSI) is a tumor phenotype linked to somatic or germline (Lynch syndrome) inactivating alterations of DNA mismatch repair genes. A broad spectrum of neoplasms exhibits MSI phenotype, mainly colorectal cancer, endometrial cancer, and gastric cancer. MSI tumors are characterized by dense immune infiltration and high load of tumor neo-antigens. Growing evidence is accumulating on the efficacy of immune checkpoint inhibition for patients treated for MSI solid tumors. We present a comprehensive overview of MSI phenotype, its biological landscape and current diagnostic methods. Then we focus on MSI as a predictive biomarker of response to immune checkpoint inhibition in the context of colorectal cancer and non-colorectal tumors.