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Resume Introduction En 2011, 11 % de l’ensemble des cancers etaient diagnostiques chez des sujets de plus de 85 ans. Avec le vieillissement actuel de la population francaise associe aux progres sanitaires, nous allons etre confrontes de plus en plus frequemment a la prise en charge des patients tres âges, et ce jusqu’a l’horizon 2050, ou la population de plus de 75 ans representera environ 15 % de la population francaise totale (contre 9,1 % en 2015). Methodes Afin de comprendre les modalites de prise en charge des patients de plus de 85 ans atteints de cancer, nous avons realise une etude observationnelle, a partir des donnees recueillies dans le reseau OncoPACA-Corse, avec pour objectif de decrire les donnees demographiques des patients tres âges, les caracteristiques de leur pathologie et d’analyser les strategies therapeutiques proposees par les oncologues aux patients de cette population. Resultats Mille trois cent cinquante-cinq fiches ont ete analysees. L’âge moyen des patients etait de 88,9 ans avec 3 % de patients âges de plus de 95 ans et un seul avait plus de 100 ans. 51,6 % etaient des femmes. Les tumeurs digestives etaient les plus representees (23,4 %), suivies des tumeurs du sein (17,7 %) et des tumeurs prostatiques (10,5 %), avec un diagnostic fait a un stade metastatique dans 20 % des cas. On constate qu’un traitement a ete propose pour pres de 85 % des patients avec une large gamme de propositions, une prise en charge palliative exclusive etait proposee dans 15 % des cas ; et lorsqu’il existait un traitement considere comme peu agressif comme l’hormonotherapie, celui etait privilegie en monotherapie.

Simple Summary The goal of precision medicine is to deliver therapy matched to a relevant actionable genetic alteration (AGA) identified in the tumor. Few data are available regarding precision medicine in advanced urological cancers (AUC), the prognosis of which remains unfavorable. Sixty-four patients with refractory AUC were enrolled in the PERMED-01 clinical trial and underwent a tumor biopsy that was then profiled using sophisticated molecular analyses. The results were discussed in real-time during a weekly molecular tumor board meeting, and patients with a relevant AGA became candidates for an eventual matched therapy. A complete molecular profile was obtained in 77% of cases and an AGA was identified in 59%. Nineteen percent of patients received a matched therapy on progression, of which 42% showed a clinical benefit. The objective response, disease control rates, and the 6-year overall survival were higher in the ``matched therapy group'' than in the ``non-matched therapy group''. Introduction. The prognosis of advanced urological cancers (AUC) remains unfavorable, and few data are available regarding precision medicine. Methods: the PERMED-01 prospective clinical trial assessed the impact of molecular profiling in adults with refractory advanced solid cancer, in terms of number of patients with tumor actionable genetic alterations (AGA), feasibility, description of molecular alterations, treatment, and clinical outcome. We present here those results in the 64 patients enrolled with AUC. DNA extracted from a new tumor biopsy was profiled in real-time (targeted NGS, whole-genome array-comparative genomic hybridization), and the results were discussed during a weekly molecular tumor board meeting. Results: a complete molecular profile was obtained in 49 patients (77%). Thirty-eight (59%) had at least one AGA. Twelve (19%) received a matched therapy on progression, of which 42% had a PFS2/PFS1 ratio >= 1.3 versus 5% in the ``non-matched therapy group'' (n = 25). The objective response and disease control rates were higher in the ``matched therapy group'' (33% and 58%, respectively) than in the ``non-matched therapy group'' (13% and 22%), as was the 6-month OS (75% vs. 42%). Conclusion: the profiling of a newly biopsied tumor sample identified AGA in 59% of patients with AUC, led to ``matched therapy'' in 19%, and provided clinical benefit in 8%.

Background The benefit of precision medicine based on relatively limited gene sets and often-archived samples remains unproven. PERMED-01 (NCT02342158) was a prospective monocentric clinical trial assessing, in adults with advanced solid cancer, the feasibility and impact of extensive molecular profiling applied to newly biopsied tumor sample and based on targeted NGS (t-NGS) of the largest gene panel to date and whole-genome array-comparative genomic hybridization (aCGH) with assessment of single-gene alterations and clinically relevant genomic scores. Methods Eligible patients with refractory cancer had one tumor lesion accessible to biopsy. Extracted tumor DNA was profiled by t-NGS and aCGH. We assessed alterations of 802 “candidate cancer” genes and global genomic scores, such as homologous recombination deficiency (HRD) score and tumor mutational burden. The primary endpoint was the number of patients with actionable genetic alterations (AGAs). Secondary endpoints herein reported included a description of patients with AGA who received a “matched therapy” and their clinical outcome, and a comparison of AGA identification with t-NGS and aCGH versus whole-exome sequencing (WES). Results Between November 2014 and September 2019, we enrolled 550 patients heavily pretreated. An exploitable complete molecular profile was obtained in 441/550 patients (80%). At least one AGA, defined in real time by our molecular tumor board, was found in 393/550 patients (71%, two-sided 90%CI 68–75%). Only 94/550 patients (17%, 95%CI 14–21) received an “AGA-matched therapy” on progression. The most frequent AGAs leading to “matched therapy” included PIK3CA mutations, KRAS mutations/amplifications, PTEN deletions/mutations, ERBB2 amplifications/mutations, and BRCA1/2 mutations. Such “matched therapy” improved by at least 1.3-fold the progression-free survival on matched therapy (PFS2) compared to PFS on prior therapy (PFS1) in 36% of cases, representing 6% of the enrolled patients. Within patients with AGA treated on progression, the use of “matched therapy” was the sole variable associated with an improved PFS2/PFS1 ratio. Objective responses were observed in 19% of patients treated with “matched therapy,” and 6-month overall survival (OS) was 62% (95%CI 52–73). In a subset of 112 metastatic breast cancers, WES did not provide benefit in term of AGA identification when compared with t-NGS/aCGH. Conclusions Extensive molecular profiling of a newly biopsied tumor sample identified AGA in most of cases, leading to delivery of a “matched therapy” in 17% of screened patients, of which 36% derived clinical benefit. WES did not seem to improve these results. Trial registration ID-RCB identifier: 2014-A00966-41; ClinicalTrials.gov identifier: NCT02342158.

In 2011, 11% of all cancers were diagnosed in people over 85 years old. With the current aging of the French population associated with health progress, we will be confronted more and more frequently with the treatment of very old patients, and this until the horizon 2050, when the population over 75 years old will represent approximately 15% of the total French population (compared to 9.1% in 2015).To understand the management methods for patients over 85 years old with cancer, we carried out an observational study, based on data collected in the OncoPACA-Corse network, with the objective to describe the demographic data of very elderly patients, the characteristics of their pathology and to analyze the therapeutic strategies proposed by oncologists to patients in this population.One thousand three hundred and fifty five cases were analyzed. The mean age of the patients was 88.9 years with 3% of patients over 95 years old and only one was over 100 years old. 51.6% were women. Digestive tumors were the most represented (23.4%), followed by breast tumors (17.7%) and prostate tumors (10.5%), with a diagnosis made at a metastatic stage in 20% of cases. We note that treatment was offered for nearly 85% of patients with a wide range of options, exclusive palliative care was offered in 15% of cases; and whena treatment considered to be not very aggressive, such as hormone therapy, was offered, it seems to be preferred as monotherapy.

348 Background: Glandular metastases (GMs) (adrenal, pancreas, thyroid, ovary, breast, or prostate) are rare in mccRCC. Several studies have observed significantly longer overall survival (OS) for GM patients treated with anti-angiogenic therapy. This study assesses outcomes from mccRCC treated with nivolumab with or without GMs. Methods: The GETUG-AFU 26 NIVOREN, phase II trial assessed the activity and safety of nivolumab in pts with mccRCC who failed antiangiogenic therapies (NCT03013335). Pts were stratified in two subgroups according to the presence of at least one GM. Specific analyzes were performed for pancreatic and adrenal metastases. Primary endpoint was OS, secondary endpoint were progression free survival (PFS) and overall response rate (ORR). Results: Between February 2016 and July 2017, among 720 patients treated by nivolumab 217 patients had GM (151: adrenal and 86: pancreatic metastases). Clinical characteristics were comparable between the two subgroups except for IMDC poor subgroup (19% vs 28%) and for Furhman grade IV (13.5% vs 23.4%) for GM and non GM respectively. Median time between metastatic disease and nivolumab was 3.2 years (y) vs 2 y for GM and non GM respectively and 2.8 vs 2.1 y with or without adrenal metastasis. There was no statistical difference in outcomes between pts with or without GMs. However, pts with adrenal metastases had worse OS (12-months survival: 64% vs 71.1%; HR 1.51 (1.19-1.92)); shorter PFS (6-months survival: 27.2% vs 36.6%; HR 1.29 (1.07-1.57)) and lower ORR (12.5% [7.6%; 19.0%] vs 23.2% [19.8%; 27.0%]; p = 0.005) than non-adrenal metastases. Conversely, patients with pancreatic metastases had significantly longer overall survival (12-months survival: 82.3% vs 67.9%; HR 0.59 (0.40-0.85)) in univariate analysis compared to non-pancreatic metastases. In multivariate analysis, only adrenal metastasis remained associated with dismal prognosis (Table). Conclusions: Adrenal metastasis is an independent poor prognostic factor for response and survival in the GETUG-AFU 26 NIVOREN phase II trial. Limited activity with nivolumab is observed for patients with adrenal metastases from mccRCC without difference with previous anti angiogenic therapy. Molecular characterization could help to identify the angiogenic profile of adrenal metastases. Clinical trial information: NCT03013335. [Table: see text]

International audience

International audience; Adrenocortical carcinomas (ACCs) are heterogeneous cancers associated with a very poor prognosis. The improvement of prognostic tools and systemic therapy are urgently needed. Targeting the immune system using checkpoint inhibitors such as PD1/PDL1 inhibitors is an attractive novel therapeutic strategy for poor-prognosis tumors. Multiple clinical trials are ongoing, including in advanced ACC. However, PDL1 expression has been studied in ACC in only one heterogeneous series of 28 clinical samples. Here, we have retrospectively analyzed PDL1 mRNA expression in 146 clinical ACC samples and searched for correlations between expression and biological and clinicopathological data, including post-operative disease-free survival (DFS). PDL1 mRNA expression was heterogeneous across samples. "PDL1-high" tumors were not associated with the classical prognostic variables but were associated with longer DFS in both uni- and multivariate analyses. High PDL1 mRNA expression was associated with biological signs of the cytotoxic local immune response. Supervised analysis between "PDL1-high" and "PDL1-low" tumors identified a robust 370-gene signature whose ontology analysis suggested the existence in "PDL1-high" tumors of a cytotoxic T-cell response, however, associated with some degree of T-cell exhaustion. In conclusion, PDL1 mRNA expression refines the prognostication in ACC and high expression is associated with longer DFS. Clinical validation at the protein level and functional validation are required to fully understand the role of PDL1 in ACC. Reactivation of dormant tumor-infiltrating lymphocytes by PDL1-inhibitors could represent a promising strategy in "PDL1-high" ACCs, supporting the ongoing clinical trials.

9561 Background: Medical treatment of lung cancer has irreversibly changed since the development of immune checkpoint inhibitors (ICI). However, immune biomarkers of efficacy are still lacking. Preliminary data in leukemia and pancreatic cancer showed that soluble immune checkpoints are associated with a reduced overall survival (OS). This led us to explore the prognostic and predictive value of soluble immune checkpoints in non-small cell lung cancer (NSCLC) patients treated with chemotherapy or ICI. Methods: We analyzed 90 advanced NSCLC patients. The pilot cohort (Rennes University Hospital, France), included 48 patients treated with platinum doublets (n = 33) or ICI (n = 15) (LOC/11-16 protocol). The confirmation cohort (Paoli-Calmettes Institute) included 42 patients treated with ICI (nivolumab or pembrolizumab) in a longitudinal prospective setting (Immunosup trial, NCT03595813). In both cohorts, enzyme-linked immunosorbent assays (ELISA) were performed in baseline plasma samples for soluble forms of PD-1, PD-L1, global BTN3, BTLA, BTN3-A1 and BTN2A1. Soluble ICI levels were linked to clinical data using Kaplan-Meier, log-rank and Cox proportional-hazards models. Cut-points were determined using maxstat package for survival, R software R 3.6.2. Results: Five soluble immune checkpoints correlated and clustered together in unsupervised analysis (PD-1, PD-L1, global BTN3, BTLA, BTN3-A1), but were not associated with ICI efficacy. In patients treated with ICI, in the pilot and confirmation cohort, a high baseline plasmatic concentration of soluble BTN2A1 was significantly associated with an improved OS (confirmation cohort with a BTN2A1 cut-point of 3.55 ng/ml: HR = 0.30, 95%CI = 0.12-0.74, p = 0.0057, median OS in BTN2A1low = 7.6 months and median OS in BTN2A1hi = 19.5 months). On the contrary, in patients treated with chemotherapy, soluble BTN2A1 concentration was not associated with overall survival. Conclusions: In advanced NSCLC patients, a high baseline plasmatic concentration of soluble BTN2A1 was correlated with improved outcomes for ICI, but not for chemotherapy, suggesting that baseline soluble BTN2A1 level is a potential predictive biomarker of ICI efficacy. Additional studies are ongoing to confirm this finding.

Background Kaposi’s sarcoma is a low-grade mesenchymal angioproliferative tumor, most commonly observed in immunocompromised individuals, such as HIV-infected patients. Iatrogenic Kaposi’s sarcoma occurs in patients undergoing immunosuppressive therapies. Rituximab is a chimeric monoclonal antibody targeted against the pan B cell marker CD20. Because of its immunosuppressive effects through reduction of mature B-cells, it may exacerbate Kaposi’s sarcoma in HIV-positive patients. Rituximab-related Kaposi’s sarcomas have been previously reported in only two HIV-negative patients and were treated surgically. Case presentation Here, we report on a Kaposi’s sarcoma that developed under rituximab treatment in a HIV-negative 55-year-old patient treated for follicular lymphoma. The lesion developed during the maintenance rituximab therapy at the rectal level with an aspect of apparent ulcerative colitis, without any cutaneous lesion. The premature stop of rituximab led to the complete regression of Kaposi’s sarcoma, without any additional specific treatment. Conclusions To our knowledge, this is the third case of Kaposi’s sarcoma diagnosed under rituximab in a HIV-negative patient, the first one at the rectal level and the first one that completely regresses after stop of rituximab. This case raises awareness of iatrogenic Kaposi’s sarcoma in HIV-negative patients treated with rituximab, and further highlights the importance of immunosuppression in the pathophysiology of disease.

Objectifs Le concept de pre-habilitation avant chirurgie oncologique est de plus en plus repandu. Plusieurs etudes ont demontre l’importance de l’anemie et de la sarcopenie sur la survie et sur les complications des traitements anticancereux. Notre etude vise a evaluer l’impact de l’anemie et de la sarcopenie sur la survie des patients traites pour tumeur de vessie infiltrant le muscle (TVIM) localisee. Methodes Nous avons analyse de facon retrospective les dossiers de 82 patients traites par chimiotherapie neoadjuvante a base de cisplatine suivie d’une cystectomie radicale pour une TVIM localisee (cT2-T4 N0 M0) entre janvier 2012 et decembre 2017. L’anemie etait definie par un taux d’hemoglobine Resultats Parmi les 82 patients, d’âge median 64,5 [31–80] ans, 20,3 % (15/82) presentaient une anemie avant traitement et celle-ci etait significativement associee a un plus faible poids (64,9 kg vs 78,4 kg, p = 0,002), un IMC plus bas (22,6 vs 26,7, p = 0,002) et un IMS plus faible (39,4 vs 48,6, p Conclusion Dans le cancer de vessie localise infiltrant le muscle, l’anemie avant traitement semble etre un facteur independant de survie, de meme que la diminution de la masse musculaire squelettique en cours de traitement. Cette etude illustre ainsi l’importance de la rehabilitation avant, pendant et apres le traitement dans la prise en charge des patients atteints d’une TVIM localisee.

e18286 Background: Several studies suggested the prognostic importance of sarcopenia in survival or treatment complications in cancer. The concept of cancer prehabilitation before surgery is gaining wide recognition. The aim of our study was to assess the impact of sarcopenia on chemotherapy toxicities and survival in patients with localized muscle invasive bladder cancer (MIBC). Methods: Between January 2012 and December 2017, patients who underwent neoadjuvant platinum-based chemotherapy (NAC) followed by radical cystectomy (RC) for cT2-T4 N0 M0 MIBC were retrospectively selected, from a single institution cohort. Using CT scan: before NAC, after NAC and after cystectomy, sarcopenia was defined according to the Lumbar Skeletal Muscle Index (SMI) in L3 assessed by two observers blinded to patients’ status. Results: 82 patients were selected, 62 men (75.6%) and 20 women (24.4%), with a median age of 64.5 years (31 to 80). 35 were considered severe sarcopenic (SMI < 35cm2/m2 for women and SMI < 50 cm2/m2 for men) before NAC. The characteristics between severe and non-severe sarcopenic patients were not significantly different except for weight (71.7 vs 81.1kg, p = 0.006) and BMI (24.0 vs 28.4kg/m2, p = 8.0x10-6). Sarcopenia pre-chemotherapy was significantly associated with nausea (p = 0.003), hypokalemia (p = 0.023) and with platinum dose-intensity during NAC (p = 0.007) but was not significantly associated with overall survival (OS) or disease-free survival (DFS). Sarcopenia post-cystectomy was correlated with the OS (HR = 0.94, CI95% [0.89-0.99], p = 0.01), but not DFS. In multivariate analysis, factors associated with OS were post cystectomy sarcopenia (p = 0.038), pN status (p = 0.001) and glomerular filtration rate (p = 0.045). Conclusions: For localized MIBC, sarcopenic status before platinum based NAC could predict some chemotherapy toxicities. After radical cystectomy, sarcopenia is an independent prognostic factor for OS. Improve patients care by prehabilitation during NAC and before surgery, using physical, nutritional and psycho-social supports, could decrease chemotherapy toxicities and improve survival particularly for sarcopenic patients.

Background Several studies suggested the prognostic importance of sarcopenia and anemia in survival or treatment complications in cancer. The aim of our study was to identify prognosis factors on chemotherapy toxicities and survival in patients (pts) with localized muscle invasive bladder cancer (MIBC). Methods Between January 2012 and December 2017, pts who underwent neoadjuvant platinum-based chemotherapy (NAC) followed by radical cystectomy (RC) for cT2-T4 N0 M0 MIBC were retrospectively selected, from a single institution cohort. Sarcopenia was evaluated according to the Lumbar Skeletal Muscle Index (SMI) in L3 using CT scan before NAC, after NAC and after RC. Pretreatment anemia was defined as hemoglobin rate Results Of 82 pts selected, 62 are men (75.6%) and 20 women (24.4%), with a median age of 64.5 years (31 to 80). Median SMI was 47.5cm2/m2 for men and 36.6 cm2/m2 for women. Pretreatment sarcopenia was significantly associated with nausea (p = 0.003), hypokalemia (p = 0.023) and with platinum dose-intensity during NAC (p = 0.007). 46 out of 74 pts had a SMI decrease greater than 5% during chemotherapy, that was associated with poor OS (HR = 4.8, CI95% [1.42-16.4], p = 0.003). Pretreatment anemia was significantly associated with OS (HR = 2.86, CI95% [1.21-6.76], p = 0.026). Transfusion during chemotherapy was not associated with survival. In multivariate analysis, factors associated with OS were SMI loss > 5% (HR = 4.62, CI95% [1,25-11,9]), positive pN status (HR = 7.66, CI95% [2,53-23,1]), histological complete response (HR = 0.22, CI95% [0,053-0,88]), pretreatment anemia (HR = 7.34, CI95% [2,26-23,8]) and ECOG status ≥ 1 (HR = 4.1, CI95% [1,41-11,9]). Conclusions For localized MIBC, sarcopenic status before NAC could predict some chemotherapy toxicities whereas pretreatment anemia could be associated with poor OS. Loss in SMI during chemotherapy is an independent prognostic factor for OS. Improve pts care by prehabilitation during NAC and before surgery, using physical, nutritional and psycho-social supports, could decrease chemotherapy toxicities and improve survival. Legal entity responsible for the study Institut Paoli-Calmettes. Funding Has not received any funding. Disclosure J. Walz: Research grant / Funding (self): Exact Imaging; Honoraria (self), Speaker Bureau / Expert testimony: Janssen; Honoraria (self), Speaker Bureau / Expert testimony: Takeda; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Blue Earth Diagnostics; Travel / Accommodation / Expenses: Ipsen. S. Dermeche: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: AstraZeneca. C. Vicier: Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Pfizer. G. Pignot: Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Astellas; Advisory / Consultancy: BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: Bouchara; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Takeda. All other authors have declared no conflicts of interest.