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PURPOSE Universal cancer peptide–based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD4+ T helper-1 response directed against telomerase. This phase Ib/IIa trial was designed to test the safety, immunogenicity, and efficacy of a three-dose schedule in patients with metastatic non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with refractory NSCLC were assigned to receive three vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg) using a Bayesian-based phase Ib followed by phase IIa de-escalating design. The primary end points were dose-limiting toxicity and immune response after three first doses of vaccine. Secondary end points were overall survival (OS) and progression-free survival at 1 year. RESULTS A total of 59 patients received UCPVax; 95% had three prior lines of systemic therapy. No dose-limiting toxicity was observed in 15 patients treated in phase Ib. The maximum tolerated dose was 1 mg. Fifty-one patients were eligible for phase IIa. The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between three dose levels. Twenty-one (39%) patients achieved disease control (stable disease, n = 20; complete response, n = 1). The 1-year OS was 34.1% (95% CI, 23.1 to 50.4), and the median OS was 9.7 months, with no significant difference between dose levels. The 1-year progression-free survival and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders ( P = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders ( P = .005), respectively. CONCLUSION UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.

Purpose:Human telomerase reverse transcriptase (hTERT) is highly expressed in >85% of human tumors and is thus considered as a good tumor-associated antigen candidate for vaccine development. We conducted a phase I study to investigate the safety, tolerability, clinical response, and immunogenicity of INVAC-1, a DNA plasmid encoding a modified hTERT protein in patients with relapsed or refractory solid tumors.Patients and Methods:INVAC-1 was either administered by intradermal route followed by electroporation or by Tropis, a needle-free injection system. Safety and tolerability were monitored by clinical and laboratory assessments. Progression-free survival and overall survival were reported using Kaplan–Meier survival analysis. Immunogenicity was studied by ELISpot, Luminex, and Flow Cytometry.Results:Twenty-six patients were treated with INVAC-1 administered at three dose levels (100, 400, and 800 μg). Vaccination was well tolerated and no dose-limiting toxicity was reported. One treatment-related grade 3 SAE was reported. Fifty-eight percent of patients experienced disease stabilization. PFS was 2.7 months, median OS was 15 months, and 1-year survival was reached for 65% of patients. INVAC-1 vaccination stimulated specific anti-hTERT CD4 T-cell response as well as cytotoxic CD8 T-cell response. No evidence of peripheral vaccine-induced immunosuppression was observed.Conclusions:INVAC-1 vaccination was safe, well tolerated, and immunogenic when administered intradermally at the three tested doses in patients with relapsed or refractory cancers. Disease stabilization was observed for the majority of patients (58%) during the treatment period and beyond.See related commentary by Slingluff Jr, p. 529

Histological diagnosis, age, number of cycles received and Overall Survival

Immunophenotyping of circulating CD4 and CD8 T cells

Number and percentage of patients reporting studytreatment-related AEs per cycle

Clinical features of patients with OS 1 year

Flow Chart

Kaplan-Meier representation of Overall Survival and Progression Free Survival

This file compiles all the results identified as "data not shown" in the manuscript

Flow Cytometry antibody references

Best Overall Response

Nowadays, resection of two (liver and peritoneum) concomitant colorectal cancer metastatic sites is no longer contraindicated. However, the oncologic outcomes of resecting peritoneal metastases (PM) occurring more than six months after resection of liver metastases (LM) are unknown.The aim of this study was to compare patients with complete cytoreductive surgery (CRS) with or without a history of previous liver resection (LR).Analysis from a prospective database of 74 patients with metachronous PM treated with CRS between 2010 and 2020.All patients had PM metachronous to primary, 64 patients underwent CRS alone (CRSa) and 10 CRS more than six months after LR (LR-CRS). There was no statistical difference between the groups for clinical or therapeutic characteristics. There were more signet ring cell/mucinous adenocarcinomas in the CRSa group than in the LR-CRS group (19% vs. 0%, p = 0.049). The median peritoneal cancer index (PCI) was 4 and 6 (p = 0.749) in the LR-CRS and CRSa groups, respectively. Median overall survival (OS) and disease-free survival (DFS) were not statistically different between the two groups with 43.6 and 13 months for the CRSa group and 31.1 months and 9.4 months for LR-CRS. Advanced age was an independent negative prognostic factor for OS and high PCI was limit significant. No prognostic factor for DFS was found.LR before CRS has no major prognostic impact. Resection of iterative liver and peritoneum metastases can achieve long-term survival.

Purpose: Human telomerase reverse transcriptase (hTERT) is highly expressed in >85% of human tumors and is thus considered as a good tumor-associated antigen candidate for vaccine development. We conducted a phase I study to investigate the safety, tolerability, clinical response, and immunogenicity of INVAC-1, a DNA plasmid encoding a modified hTERT protein in patients with relapsed or refractory solid tumors. Patients and Methods: INVAC-1 was either administered by intradermal route followed by electroporation or by Tropis, a needle-free injection system. Safety and tolerability were monitored by clinical and laboratory assessments. Progression-free survival and overall survival were reported using Kaplan–Meier survival analysis. Immunogenicity was studied by ELISpot, Luminex, and Flow Cytometry. Results: Twenty-six patients were treated with INVAC-1 administered at three dose levels (100, 400, and 800 μg). Vaccination was well tolerated and no dose-limiting toxicity was reported. One treatment-related grade 3 SAE was reported. Fifty-eight percent of patients experienced disease stabilization. PFS was 2.7 months, median OS was 15 months, and 1-year survival was reached for 65% of patients. INVAC-1 vaccination stimulated specific anti-hTERT CD4 T-cell response as well as cytotoxic CD8 T-cell response. No evidence of peripheral vaccine-induced immunosuppression was observed. Conclusions: INVAC-1 vaccination was safe, well tolerated, and immunogenic when administered intradermally at the three tested doses in patients with relapsed or refractory cancers. Disease stabilization was observed for the majority of patients (58%) during the treatment period and beyond. See related commentary by Slingluff Jr, p. 529

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

TPS9152 Background: Gal-3 is a protein that binds specifically to N-acetylglucosamine-expressing carbohydrates, which are upregulated on key tumorigenic cell surface proteins. Gal-3 is widely over-expressed in the tumor microenvironment and is generally linked to poor outcomes. Gal-3 regulates immune cell function of T cells and macrophages, and promotes neovascularization and fibrosis [Peng Cancer Res 2008; Markowska J Biol Chem 2011; Kouo Cancer Immunol Res 2015]. Gal-3 sequesters interferon gamma, reduces T-cell influx, and contributes to tumor cell evasion of the immune system via LAG-3 activation [Chen PNAS 2009; Gordon-Alonso Nat Commun 2017]. Gal-3 has been identified as a marker of resistance to checkpoint inhibitors (CPIs); patients with stage IV NSCLC with high Gal-3 levels (> 70% Gal-3 immunohistochemical staining) have been shown to be resistant to the CPI pembrolizumab [Capalbo Int J Mol Sci 2019]. Animal data indicate synergy between CPI therapy and Gal-3 inhibition [Vuong Cancer Res 2019; Zhang FEBS Open Bio 2021]. Thus, inhibiting Gal-3 together with CPI-based immunotherapy may enhance tumor-specific immune responses, and overcome CPI resistance. Methods: GALLANT-1 (NCT05240131) is a 3-part, placebo-controlled phase Ib/IIa trial that will investigate safety and efficacy of GB1211 (a Gal-3 inhibitor) + atezo vs placebo + atezo in patients with advanced NSCLC. Part A will include 8–12 patients and study safety and tolerability of 200 mg and 400 mg GB1211 twice-daily + atezo (open-label). Primary endpoint is number of adverse events (AEs) after 12 weeks’ treatment and will determine the dosage for Part B. Part B will include 75–94 patients, and is a randomized, double-blind study of GB1211 + atezo or placebo + atezo. Primary endpoints are safety (number of AEs) and efficacy (percentage change from baseline in the sum of longest diameter of target lesions after 12 weeks’ treatment). Part C is an expansion study including patients from Parts A and B, with safety and efficacy assessments. Eligibility criteria: advanced or metastatic stage IIIB or IV NSCLC adenocarcinoma; measurable disease per RECIST v1.1; expression of programmed death ligand-1 on ≥50% of tumor cells; eligible for 1200 mg atezo every 3 weeks. Exclusion criteria: symptomatic, untreated, or actively progressing central nervous system metastases; prior systemic chemotherapy for treatment of recurrent advanced or metastatic disease, except if part of neoadjuvant/adjuvant therapy; prior treatment with immune CPIs and/or GB1211; presence of EGFR mutation and ALK, ROS1, and RET alterations; treatment with antineoplastic or systemic immunotherapeutic agents prior to first GB1211 dose; severe infectious disease < 4 weeks prior to first GB1211 dose; active hepatitis B or C, HIV, or COVID-19. The study is being initiated; updated enrollment status will be presented at the meeting. Clinical trial information: NCT05240131.

2049 Background: hPG80 (circulating progastrin) is a protein secreted by many cancer types, playing a role in tumorigenesis by regulating cancer stem cells, angiogenesis, proliferation/differentiation and decreasing apoptosis. hPG80 is detectable in plasma of cancer patients and previous studies have shown its prognostic role in various cancers. Given the lack of circulating biomarker in glioblastoma, we evaluated the prognostic value of plasma hPG80 in patients with IDH wild type glioblastoma Methods: This multicentric retrospective study included IDHwt glioblastoma patients treated with standard radio-chemotherapy. The ELISA DxPG80.lab kit (Biodena Care, Lausanne, Switzerland) was used to measure hPG80 levels after surgery with a detection threshold of 1 pM in all plasma EDTA samples according to the manufacturer’s instruction. The prognostic impact of hPG80 was evaluated on patient’s progression-free survival (PFS) and overall survival (OS). Results: We included 70 patients (38 males /32 women) with a median age of 64 years (Range 19 - 84). Karnofsky index was > 70% in 52 (91%) of 57 evaluable patients. Tumor biopsy (B), partial resection (PR), complete resection (CR) were performed in 22, 25 and 23 patients respectively. MGMT promotor was methylated in 22 (40%) of the 55 evaluable patients. After surgery, hPG80 was detected in 48 (69%) patients (hPG80+) with a median concentration of 9.52 pM (IQR 5.21 - 21.20). Complete surgery was associated with undetectable levels of hPG80 (52% (CR) vs 28% (PR) vs 14% (B), p = 0.006) and lower concentration if hPG80+ (CR: 5.8 pM [IQR 1.92 - 11.38] vs PR: 12.84 pM [IQR 8.09 - 37.09]; p = 0.04 vs B: 9.86 pM [IQR 4.66 - 21.63]; p = 0.16). With a median follow-up of 39 months (22.4-NR), 86% of patients had progressed and 70% had died. In univariate analysis, hPG80 positivity was associated with PFS (5.6m vs 8.5m, p = 0.053) and OS (14.5 vs 22m, p = 0.04) in hPG80+ vs hPG80- patients respectively. hPG80+ patients with complete surgery had worse median OS than hPG80- patients (14.5 vs 22.0 m; p = 0.051 respectively. Cox proportional hazards model did not fit for covariate analysis. Conclusions: Our findings show that hPG80 could serve as a new circulating prognostic biomarker in IDHwt glioblastoma patients treated with radio-chemotherapy. Further explorations are ongoing in larger cohorts including longitudinal evaluation during the course of the disease.

IntroductionGlioblastoma (GBM) is frequent in elderly patients, but their frailty provokes debate regarding optimal treatment in general, and the standard 6-week chemoradiation in particular, although this is the mainstay for younger patients. MethodsAll patients with newly diagnosed GBM and age ≥ 70 who were referred to our institution for chemoradiation (RCT) were reviewed from 2004 to 2018. MGMT status was not available for treatment decision at that time. The primary endpoint was overall survival (OS). Secondary outcomes were progression-free survival (PFS), early adverse neurological events without neurological progression ≤ 1 month after RCT and temozolomide hematologic toxicity assessed by CTCAE v5. Results128 patients were included. The median age was 74.1 (IQR: 72-77). 15% of patients were ≥80 years. 62.5% and 37.5% of patients fulfilled the criteria for RPA class I-II and III-IV, respectively. 81% of patients received the entire RCT and 28% completed the maintenance temozolomide. With median follow-up of 11.7 months (IQR: 6.5-17.5), median OS was 11.7 months (CI95%: 10-13 months). Median PFS was 9.5 months (CI95%: 9-10.5 months). 8% of patients experienced grade ≥3 hematologic events. 52.5% of patients without neurological progression had early adverse neurological events. Post-operative neurological disabilities and age ≥80 were not associated with worsened outcomes. Conclusions6-week chemoradiation was feasible for “real-life” elderly patients diagnosed with glioblastoma, even in the case of post-operative neurological disabilities.

Glioblastoma (GBM) is frequent in elderly patients, but their frailty provokes debate regarding optimal treatment in general, and the standard 6-week chemoradiation (CRT) in particular, although this is the mainstay for younger patients. All patients with newly diagnosed GBM and age ≥ 70 who were referred to our institution for 6-week CRT were reviewed from 2004 to 2018. MGMT status was not available for treatment decision at that time. The primary endpoint was overall survival (OS). Secondary outcomes were progression-free survival (PFS), early adverse neurological events without neurological progression ≤ 1 month after CRT and temozolomide hematologic toxicity assessed by CTCAE v5. 128 patients were included. The median age was 74.1 (IQR: 72–77). 15% of patients were ≥ 80 years. 62.5% and 37.5% of patients fulfilled the criteria for RPA class I–II and III–IV, respectively. 81% of patients received the entire CRT and 28% completed the maintenance temozolomide. With median follow-up of 11.7 months (IQR: 6.5–17.5), median OS was 11.7 months (CI 95%: 10–13 months). Median PFS was 9.5 months (CI 95%: 9–10.5 months). 8% of patients experienced grade ≥ 3 hematologic events. 52.5% of patients without neurological progression had early adverse neurological events. Post-operative neurological disabilities and age ≥ 80 were not associated with worsened outcomes. 6-week chemoradiation was feasible for “real-life” elderly patients diagnosed with glioblastoma, even in the case of post-operative neurological disabilities. Old does not necessarily mean worse.

Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2, 95%CI, 9–14.3, p = 0.001) and &lt, 20 pack-years (HR = 4.8, 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.

Introduction Glioblastoma (GBM) is frequent in elderly patients, but their frailty provokes debate regarding optimal treatment in general, and the standard Stupp regimen in particular, although this is the mainstay for younger (

Objectives The occurrence of immune-related myositis (irM) is increasing, yet there are no therapeutic guidelines. We sought to analyse the current therapeutic strategies of irM and evaluate the outcomes of immune checkpoint inhibitors (ICIs) rechallenge. Methods We conducted a nationwide retrospective study between April 2018 and March 2020 including irM without myocardial involvement. Depending on the presence of cutaneous signs or unusual histopathological features, patients were classified into two groups: typical or atypical irM. Therapeutic strategies were analysed in both groups. The modalities and outcomes of ICI rechallenge were reviewed. Results Among the 20 patients, 16 presented typical irM. Regardless of severity, most typical irM were treated with steroid monotherapy (n = 14/16) and all had a complete response within ≤3 weeks. The efficacy of oral steroids for non-severe typical irM (n = 10) was the same with low-dose (≤0.5 mg/kg/day) or high-dose (1 mg/kg/day). Severe typical irM were successfully treated with intravenous methylprednisolone. Atypical irM (n = 4) had a less favourable evolution, including one irM-related death, and required heavy immunosuppression. ICIs were safely reintroduced in nine patients presenting a moderate (n = 6) or a severe (n = 3) irM. Conclusion Our data highlight that steroid monotherapy is an effective treatment for typical irM, either with prednisone or with intravenous methylprednisone pulses depending on the severity. The identification of unusual features is important in determining the initial therapeutic strategy. The outcomes of rechallenged patients are in favour of a safe reintroduction of ICI following symptom resolution and creatin kinase (CK) normalization in moderate and severe forms of irM.

Introduction Un depistage cible du melanome est recommande en France. Le SAMScore est un auto-questionnaire valide permettant le reperage des personnes a risque en soins primaires. Il est cependant peu connu et faiblement utilise en pratique quotidienne. L’objectif de l’etude etait d’evaluer le taux de reponse des patients au SAMScore lorsque celui-ci est remis par leur medecin generaliste au decours d’une consultation. Materiel et methodes Etude observationnelle aupres de 14 medecins generalistes inscrits au CDOM du departement, recrutes par mail. Le questionnaire a ete distribue en fin de consultation a tous leurs patients consultant au cabinet pendant 4 journees. Les patients avaient 4 mois pour y repondre et le ramener a leur medecin, qui devaient verifier le score et l’integrer au dossier. Le critere de jugement principal etait le taux de participation au questionnaire. Analyses statistiques descriptives. Resultats Sur les 946 questionnaires distribues, 515 ont ete rendus par les patients. Ce taux de participation de 54,4 % [27,6–68,2 %] variait selon les medecins (p Discussion La force de cette etude est l’utilisation en situation reelle d’un outil valide. La principale limite est un biais de recrutement des medecins participants volontaires. Plus d’un patient sur deux a participe au SAMScore et pres de la moitie etait a risque de melanome. Cette strategie de depistage cible pourrait devenir systematique avec plus de 2/3 des scores integres aux dossiers medicaux. Pour cela, nous devons ameliorer la formation des medecins generalistes et travailler sur une cooperation en reseau avec les dermatologues.

Introduction Targeted therapies such as tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of lung adenocarcinoma, and detection of activating mutations of genes such as EGFR or anaplastic lymphoma kinase gene ( ALK ) is now mandatory in the clinical setting. However, additional targetable alterations are continuously being described and forcing us to adapt our detection methods. Here we have evaluated the ability of eight amplicon-based next-generation sequencing (NGS) panels to detect the recently described mesenchymal epithelial transition factor ( MET ) exon 14 ( MET ex14) alterations or new mutations conferring resistance to TKIs. Methods A total of 191 tumor samples from patients with NSCLC were screened for MET ex14 mutations by Sanger sequencing, and 62 additional cases were screened by Sanger sequencing and two amplicon-based NGS panels. In silico comparison of eight commercially available targeted NGS panels was also performed for the detection of MET ex14 alterations or ALK , ROS1, or EGFR resistance mutations. Results NGS analysis of the positive MET ex14 cases revealed a false-negative case because of amplicon design. Moreover, in silico analysis revealed that none of the eight panels considered would be able to detect more than 63% of literature-reported cases of MET ex14 mutations and similar limitations would be expected with new ALK , ROS1, or EGFR resistance mutations. Conclusions We have illustrated major limitations of commercially available amplicon-based DNA NGS panels for detection of MET ex14 and recently described resistance mutations to TKIs. Documented choice of available panels and their frequent reevaluation are mandatory to deliver the most accurate data to the clinician for therapeutic decisions.

Purpose: Pancreatic metastases (PM) from renal cell carcinoma (RCC) have been associated with long-term survival. The aim of this study was to evaluate the outcome of RCC patients with multiple glandular metastases (MGM) treated with targeted therapies (TTs). Methods: Sixty-four MGM patients treated between 1993 and 2014 were retrospectively identified from a database of 274 RCC patients with PM from 11 European centers. The survival of MGM patients was compared with that of both patients with PM only and a cohort of 325 RCC patients with non-GM (control group) treated with TTs. Survival was estimated using the Kaplan-Meier method and was statistically compared using the log-rank test. Results: Fifty-six patients (88%) had at least 2 MGM, 7 patients (11%) had 3 MGM and 1 patient had 4 MGM, while non-GM were present in the remaining patients. The median overall survival (OS) was 54.2 months for MGM and 73.4 months for patients with PM only. The median OS in the control group was 22.7 months and statistically inferior to both MGM (p < 0.001) and PM patients (p < 0.001). Conclusion: MGM from RCC are associated with a remarkable survival. Despite some limitations, these findings suggest that GM might be considered a predictor of a favorable prognosis.

Introduction Les myopathies inflammatoires induites par l’immunotherapie (MII) sont rares mais potentiellement graves. Leur prise en charge n’est pas standardisee et interroge sur la possibilite de reprise du traitement. L’objectif de cette etude est de preciser les caracteristiques des MII sous anti-PD-1, leur traitement et l’impact d’une reprise de l’immunotherapie (IT) par la suite. Materiel et methodes Etude francaise multicentrique retrospective incluant des patients ayant developpe une MII sous anti-PD-1. Les donnees ont ete recueillies dans les services d’oncodermatologie et d’oncologie thoracique d’avril 2018 a mai 2019, avec 10 centres participants. Resultats Dix-huit patients (2 en situation adjuvante) traites par anti-PD1 et presentant une MII ont ete identifies, dont 3 dermatomyosites. Le delai median de survenue apres initiation de l’IT etait de 36 jours [8–388]. Douze patients avaient une MII de grade CTCAE 1-2 et 6 de grade ≥ 3, dont 2 deces. L’atteinte musculaire peripherique (n = 17) predominait sur les ceintures (n = 10). Des signes de gravite ORL ou respiratoire etaient presents dans 50 % des cas avec 1 cas de myocardite associee. Les CPK etaient augmentes dans 89 % des cas avec un taux median de 9,8 N [1,2–55,7]. Le diagnostic etait conforte par une IRM musculaire, un Pet-scan et/ou un EMG dans 86 % des cas et systematiquement par la biopsie musculaire lorsqu’elle etait faite (n = 11). Le DOT myosite etait negatif dans 88 % des cas. Seize patients ont recu une corticotherapie generale (CTG). Parmi eux, 37 % ont eu des bolus de methylprednisone + CTG ≥ 1 mg/kg/jour, 44 % une CTG ≥ 1 mg/kg/jour sans bolus et 19 % une CTG faible dose. Pour 4 patients, des IgIV (n = 4), du methotrexate (n = 1) ou du rituximab (n = 1) ont ete introduits apres echec de la CTG et pour une presentation plus severe de grade ≥ 3. La decroissance de la CTG a ete rapide avec une mediane de 11 semaines [4–59]. Pour 89 % des patients les symptomes ont ete resolutifs sans rechute avec un recul median de 319 jours [90–1126]. Apres remission de la MII, une IT a ete reprise chez 7 patients soit avec le meme (n = 3) ou un autre (n = 3) anti-PD-1, soit avec l’ipilimumab (n = 1), dans un delai median de 120 jours [30–434] apres la derniere cure d’anti-PD-1. Les anti-PD-1 n’ont pas ete interrompus pour 2 cas de MII de grade 1. Parmi ces 9 patients ayant soit poursuivi soit ete retraites par IT, 5 (56 %) ont eu un benefice oncologique et sont toujours en cours de suivi. Aucune rechute de la MII n’a ete rapportee suite a la reprise du traitement. Conclusion Les MII surviennent precocement sous IT avec un phenotype different des myopathies inflammatoires classiques. Il ressort que : – la posologie de la CTG peut etre adaptee a la severite, – une duree courte de CTG permet une resolution complete des MII plus rapide que dans les formes classiques, – le benefice des autres immunosuppresseurs n’est pas certain, – la reprise d’une IT par la suite est possible sans rechute.

Outcomes in cancer patients after unplanned ICU admission was reassessed.retrospective cohort of patients with solid tumours admitted to ICU over a 10 years period.622 patients (age 62 [53-70]) were analysed. The most common primary sites of cancer were lung (n = 133; 21.4%) and digestive tract (n = 126; 20.2%) The ICU mortality rate was 22.2% (n = 138). Among 470 ICU survivors, the 1-year mortality was 41.3% (95% CI, 36-45.9) (n = 167). Factors independently associated with 1-year mortality were ICU admission after 2010 (HR 0.53 (0.37-0.76), p .001), disease status (respectively, HR = 1.88 (1.0.2-3.45), p = .002) for locally advanced cancer and HR = 2.23 (1.35-3.67), p = .003) for metastatic cancer), poor performance status (HR = 1.58 (1.08-2.31), p = .019), newly diagnosed cancer at ICU admission (HR = 2.02 (1.28-3.20), p = .003), inability to receive oncologic treatment after ICU discharge (HR = 5.34 (3.49-8.18), p .001) and decision to withhold life-sustaining treatment during ICU stay (HR = 2.34 (1.50-3.65), p .001).Among the factors associated with one-year mortality after ICU discharge, the possibility of receiving oncologic treatment after ICU discharge seems crucial.

Introduction Immune checkpoint inhibitors (ICIs) have improved cancer prognosis but have not been evaluated specifically in sarcomatoid carcinoma (SC), a rare lung cancer subtype with poor prognosis. As such, our study sought to retrospectively assess the efficacy of ICI in SC. Methods All consecutive patients with centrally confirmed SC treated using ICI as a second-line treatment or beyond between 2011 and 2017 were enrolled. Programmed death-ligand 1 (PD-L1) tumor expression was assessed using immunohistochemistry (SP263 clone) and the tumor mutational burden (TMB) with the Foundation One panel. TMB was considered high if it was greater than or equal to 10 mutations per megabase. Results Overall, 37 patients with SC were evaluated, predominantly men (73%) with a median age of 63.2 years (36.8–79.7) and who were current or former smokers (94.6%). Immunotherapy (nivolumab, 86.5% of cases) was given as a second-line treatment in 54% of the patients and as third-line treatment or beyond in 46% of the patients. The objective response rate was 40.5% and disease control rate was 64.8%, regardless of PD-L1 status. Median overall survival was 12.7 months (range: 0.3–45.7). One-third of patients exhibited early progression. The median PD-L1 expression was 70% (0–100). There was a trend toward higher PD-L1 expression in responsive diseases, with an objective response rate of 58.8% in patients with PD-L1+ and 0% in the one patient with PD-L1- (p = 0.44). The median TMB was 18 (4–39) mutations per megabase, with 87.5% of the cases displaying a high TMB. There was a trend toward higher TMB in responders versus stable or progressive diseases (p = 0.2). Conclusions Patients with SC exhibited high response rates and prolonged overall survival under ICI treatment. These data support the prospective investigation of ICI in patients with SC who are under first-line treatment.

International audience; Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

International audience; Venous thromboembolism (VTE) is a major common complication in cancer patients. Risk-adapted thromboprophylaxis and antithrombotic therapy for patients diagnosed with VTE can reduce the recurrence of VTE events. Thrombotic risk varies according to cancer type, stage, and comorbidities. The current review analyzes most recent data and provides clinical guidance for the management of women with cancer-associated thrombosis.

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385 Background: Personalized chemotherapy based on tumor marker decline is the new standard in poor prognosis germ-cell tumor in Europe since 2014 (GETUG 13, Lancet, Fizazi et al). The purpose of this study was to analyze the reproducibility of the princeps study in patients not selected in clinical routine between 2014 and 2018. Methods: Patients (pts) were eligible if they had at least one criteria of IGCCCG classification for poor prognosis group. They had to be treated according the study terms of GETUG 13 study and did not received prior treatment. They had to received 1 BEP (Bleomycin, Etoposide, Cisplatin). Tumor markers (HCG and AFP) were dosed between day 18 and 21. Then, they received 3 additional BEP if they had favorable tumor marker decline or intensive chemotherapy if they had unfavorable decline. Results: This retrospective study included 104 patients in 14 french centers treated between 2013 and 2018: 22,1 % (n = 23) in the favorable group (Fav), 77,9 % (n = 81) in the unfavorable group (Unfav). Thirty-two pts had PS ≥ 2. In Unfav, there were more pts with HCG > 50 000 UI/L (44,2 % vs 13 %, p = 0,0067), neutrophil-to-lymphocyt ratio was also higher (median 6,4 vs 4,5, p = 0,0199). At cycle 1, all pts received BEP in Fav and 87,5 % (n = 70) in Unfav. After chemotherapy and surgery, 65,2 % in Fav and 41,3 % in Unfav obtained complete response. At 30 months (median follow-up), Fav-OS was 80,5 % (IC95% 55,8 – 92,2) and Unfav-OS was 64,4 % (IC95% 52 – 74,4). At 30 months, rates were 69,6 % (IC95% 46,6 -84,2) and 63.5 % (IC95% 51,9 – 73) respectively. In GETUG 13 study, 3-years OS was 84 % in Fav and 73 % on Unfav; 3-years PFS was 70 % and 59 % respectively. Seven pts died because of toxicity in Unfav (No one in Fav). Neuropathy, anemia and thrombopenia were more frequent in Unfav. Salvage high-dose chemotherapy with stem-cell transplant was required in 4 (66,7 %) pts in Fav and 8 (36,4 %) pts in Unfav. Conclusions: This study showed a reproducibility of the princeps study in terms of PFS and OS. Toxicity seemed more important in real world. For the congress, results will be reported with 50 additional pts.

589 Background: The Katherine trial has shown that adjuvant T-DM1 improved invasive disease free survival (iDFS) of patients with HER2+ breast cancer who did not achieve a pathological complete response (pCR) with trastuzumab-based neoadjuvant chemotherapy (NAC). However, some subgroups may benefit less from this treatment escalation. Methods: All HER2+ breast cancer patients treated with trastuzumab-based NAC between 2006 and 2016 were retrieved from our institution’s database. Neo- or adjuvant T-DM1 was an exclusion criterion. We then selected the patients who did not achieve a pCR and analyzed the outcome (iDFS and overall survival (OS)) according to ypT, ypN and several factors analyzed in the Katherine trial. Results: Out of the 182 patients, 117 patients reached the inclusion criteria. Patient’s characteristics were similar to the trastuzumab arm of the Katherine trial. With a median follow-up of 75.4 months (29.3–149.7), 28 events (24%) occurred, among which 22 distant relapses. In univariate analysis, ≤ypT1 vs > ypT1, ypN0 vs ypN+, no capsular rupture, signs of histological response (Sataloff not D in T or N) were associated with a better iDFS. In multivariate analysis, only ypT status remained significant. Of note, patients with ≤ypT1 (ypTis, ypT0, ypTmic, ypT1) (n = 81; 69%) had an excellent outcome: 3 years (y) and 5y iDFS rates of 90% (83.6-96.8) and 88.6% (81.9-95.9) respectively. The remaining patients (n = 36; 31%) had a significantly lower 3y and 5y iDFS: 69.2% (55.6-86.2) and 59.5% (45-78.6) respectively (p = 0.0017). OS in a multivariate analysis was also improved in pts with the smaller residual and/or node negative disease (3y OS rates of 100% (100-100) vs 92.1% (85.7-99); 5y OS rates of 96% (90.7-100) vs 81.1% (71.6-91.9); p = 0.02). Conclusions: In the absence of pCR after trastuzumab-based NAC, patients with pathological response scored as ≤ypT1 (ypTis,ypT0, ypTmic, ypT1) have an excellent outcome. These patients may derive less benefit from adjuvant T-DM1.

BACKGROUND: BRCA1 and BRCA2 are two major susceptibility genes for breast cancer. We aimed to compare clinicopathological features and outcomes in BRCA1/2-mutation carriers patients, in patients with a family history suggesting hereditary breast cancer (HBC) without BRCA mutation (Eisinger score ≥ 5), and in patients with sporadic disease. METHODS: We retrospectively reviewed clinical and pathological data of 56 BRCA-mutation carriers (29 BRCA1, 27 BRCA2), 85 HBC patients and 70 sporadic breast cancer patients treated at Saint-Louis hospital between 1987 and 2017. Sporadic breast cancer patients were free from family history of cancer and randomly extracted from our database. We recorded age, clinicopathological features of breast tumors (tumor size, grade, nodal status, hormone receptor and c-erbB2 status), treatment type, ipsilateral relapse, contralateral breast cancer occurrence, distant metastasis and outcome (disease-free and overall survival). RESULTS: BRCA-mutated and HBC patients showed earlier age of onset of tumor (respectively 36, 42 and 40 years) than sporadic breast cancer patients (54 years, p Citation Format: Stéphanie Bécourt, Ludovic Doucet, Odile Cohen-Haguenauer, Florence Ledoux, Olivia Nguyen, Luca Campedel, Sylvie Giacchetti, Caroline Cuvier, Marc Espié, Luis Teixeira. Comparison of clinicopathological features and outcome of breast cancer in BRCA-mutation carriers, in patients with a family history without BRCA-mutation and in patients with sporadic disease [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-03-06.

International audience; Introduction: Immune checkpoint inhibitors (ICIs) have revolutionised cancer care especially in lung cancer. New response patterns have been described under ICIs such as pseudo-progression or hyper-progressive disease (HPD). The definition of HPD is yet to be consensual. The aim of this study was to suggest a clinical definition of nivolumab-refractory patients and find factors associated with this entity.Methods: We performed a multi centric retrospective study including all patients who received nivolumab for the treatment of advanced non-small cell lung cancer (NSCLC) during the French authorisation for temporary use in 2015.Results: 303 patients were included in the cohort and 292 had details on the number of nivolumab injections received. 57 patients (20%) were nivolumab-refractory. These patients had worse PS at nivolumab initiation (p

Background: Nivo is the gold standard for second line treatment of advanced NSCLC. Hyper-progression (HP) is a form of early progression observed during treatment by immune checkpoint inhibitors and usually fatal which has been poorly evaluated. Aim: To determine factors associated with HP in patients with advanced NSCLC treated with nivo. Methods: Our multi-center retrospective study included all patients with advanced NSCLC receiving nivo during the French authorisation for temporary use between January and December 2015. HP was defined as progression or death occurring before any tumour evaluation or before 3 injections of nivo. Results: 263 patients were included with 14.6-months median follow-up. Median overall survival (OS) at the date of cut-off was 10.1 months [95% CI (7.7 – 13.0)]. Baseline characteristics were as follows: 65 years, 68% male, 92% smokers, 62% with adenocarcinoma histology, 28% with squamous cell carcinoma and 10% with other, 66% with PS 0-1 at nivo initiation. Fifty-one patients (19%) had progressed before receiving 3 injections of nivo and a further 51 (19%) before receiving 5. Patients who presented with more rapid progression had worse PS at nivo initiation (p=0.042), worse PS at first nivo evaluation (p Conclusion: Nearly 20% of our patients experienced HP before 3 injections of nivo resulting in worsening OS. HP needs to be further studied in order to better select patients who will truly benefit from immune checkpoint inhibitors.

Background Abiraterone acetate (AA), an androgen biosynthesis inhibitor, is now a standard of care for men with metastatic, castration-sensitive and castration-resistant prostate cancer (mCRPC). Data exploring real-world toxicity and outcomes are scarce. Methods Retrospective study on unselected patients with mCRPC on AA plus steroids. Results 93 patients were included in the study. Median duration of treatment by AA was 7.5 months (95% CI 5.7–12) among the 58 patients pretreated with chemotherapy, versus 12.7 months ( 95% CI 8.2–35.9) among the 33 chemo-naive patients. Median survivals would reach 13.4 months (95% CI 10.2–19.1) and 36.4 months (95% CI 24.7–41.5) respectively. Rates of hypokalemia, peripheral edema, hypertension, cardiac failure, and overall survival assessments in patients with and without prior chemotherapy were similar to that previously reported in phase 3 randomized trials. The median survival time without adverse event of special interest was 7.5 months for hypokalemia and hypertension, and 5.3 months for liver-function test abnormalities (it was not reached for cardiac disorders). Conclusion Our findings provide further evidence for the survival benefits of AA with a low frequency of additional adverse events among unselected patients. In patients who have not developed hypokalemia or a transaminase increase within 7.5 and 5.3 months respectively, a lighter systematic monitoring may be considered.

Resume La comprehension moleculaire du cancer de la prostate resistant a la castration a fait ces dernieres annees l’objet d’un changement de paradigme. Le concept d’hormono-resistance ou d’independance aux androgenes a disparu depuis la preuve de l’efficacite de nouveaux traitements ciblant le recepteur aux androgenes chez des patients progressant sous privation androgenique. Cela sous-tend donc que la survie des cellules cancereuses reste dependante des androgenes. L’objet de cette revue est de resumer l’etat des connaissances sur les mecanismes developpes par les cellules du cancer de la prostate pour se developper sous privation androgenique.

Si la cystectomie demeure le traitement local de reference pour les tumeurs de vessie infiltrant le muscle, les recidives metastatiques sont frequentes et suggerent le developpement precoce de micrometastases. L’administration d’une chimiotherapie perioperatoire apparait donc logique pour reduire leur frequence. Les donnees de la litterature plaident pour l’administration d’une chimiotherapie neoadjuvante (CNA) a base de cisplatine en raison du benefice de survie demontre. Pour la majorite des histologies non urotheliales ainsi que pour les patients ne pouvant pas recevoir de cisplatine, la cystectomie est indiquee d’emblee. L’identification recente de sous-types moleculaires permettra dans un futur proche de selectionner les patients les plus a meme de beneficier des traitements perioperatoires et de proposer des therapies ciblees adaptees aux voies moleculaires impliquees.

Nivolumab for the treatment of advanced nonsmall cell lung cancer (NSCLC) evaluated in phase III trials showed 50% progression at first evaluation, but better overall survival (OS), suggesting regained efficacy of treatments given thereafter. We aimed to evaluate the efficacy of nivolumab and of next treatment received after nivolumab progression in patients with advanced NSCLC. Our multicentre retrospective study included all patients receiving nivolumab between January and December 2015. The primary end-point was progression-free survival (PFS) of treatment given after nivolumab. The 303 patients had the following characteristics: median age 63 years, 69% males, 92% smokers, 67% performance status 0–1 and 61% adenocarcinoma. Nivolumab was given as second-line treatment in 40% of patients. With 13.7 months of median follow-up, nivolumab PFS and OS were 2.6 and 11.3 months, respectively. At the cut-off analysis 18% were controlled under nivolumab, 14% were deceased and 5% were lost to follow-up under nivolumab. Among the 191 (63%) patients eligible for post-nivolumab (PN) treatment, 115 (38%) received further treatment and were characterised by better performance status (p=0.028) and by receiving more injections of nivolumab (p=0.001). Global PN-OS and PN-PFS were 5.2 and 2.8 months, respectively. Drugs most frequently used after nivolumab were gemcitabine (23%), docetaxel (22%) and erlotinib (16%), with median PFS of 2.8, 2.7 and 2.0 months, respectively. Nivolumab produced similar efficacy as in phase III trials, although patients received nivolumab later and had worse performance status. 38% received treatment after nivolumab progression with efficacy comparable to historical second-line trials., Efficacy of nivolumab in nonsmall cell lung cancer http://ow.ly/k2uX30iGZbY

Background: Nivo is authorised for 2nd line treatment of advanced NSCLC. Although 50% of pts progressed at 1st Nivo evaluation in phase III trials overall survival (OS) favoured Nivo suggesting better efficacy of treatments given post Nivo. Aim: To evaluate the efficacy of the next treatment received after Nivo progression in advanced NSCLC patients receiving Nivo. Methods: Our multi-center retrospective study included all pts receiving Nivo during the French authorisation for temporary use (ATU) between Jan and Dec 2015. Primary end point was progression free survival (PFS) on the next treatment given post Nivo. Results: Characteristics of the 297 pts included at Nivo initiation: 65 years, 69% males, 90% smokers; 61% adenocarcinoma, 29% squamous and 10% others; 68% PS 0-1. Nivo was given in 40%, 29% and 31% in 2nd, 3rd or ≥4th line treatment respectively. With a 22 months (mos) median follow-up, PFS on Nivo was 2,6 mos (95%CI [2.1-3.5]) and OS 10,9 mos [8,5 -NR]. 32% of pts died before further treatment, 4% were lost of follow-up, 24% were controlled, 5% were progressive but did not receive post Nivo treatment and 34% (n=101) received post Nivo treatment. Characteristics of these pts did not differ from that of the overall population. Most frequent drugs used were: 24% gemcitabine (G), 21% docetaxel (D) and 15% Erlotinib (E). The PFS after Nivo was 2.7 mos [2.1-3.4]; 2.7 mos for G, 2.7 mos for D and 1.8 mos for E. Treatment duration was >5 mos for G and >4 mos for D in 25% of pts. Conclusion: Nivo produced similar efficacy as in phase III trials. Although only 34% of pts received post Nivo treatment, 25% had longer treatment duration on G or D.

2642 Background: INVAC-1 is an optimized DNA plasmid encoding an inactive form of human Telomerase Reverse Transcriptase (hTERT), a universal tumor antigen expressed in most of human tumors with little or no expression in somatic cells. We report here the final results of a First-In-Human Phase I study evaluating INVAC-1 as a single agent in patients (pts) with advanced solid tumors, ended in June 2018. Methods: A two center Phase I trial evaluated INVAC-1 given monthly for a minimum of 3 cycles and up to 9 cycles by intradermal injection followed by electroporation (n = 20) or using a needle-free injection system (n = 6). Primary objectives included safety, tolerability and dose limiting toxicities to identify the maximum tolerated dose and recommended phase 2 dose. Secondary objectives included immune response (assessed by IFN-γ Elispot) and anti-tumor activity. Immuno-monitoring included detection of autoantibodies, lymphocyte phenotyping and inflammatory cytokine levels in blood. Anti-tumor activity was evaluated through RECIST 1.1 adapted to immune response, and plasma circulating tumor DNA (ctDNA). Results: 26 pts with refractory/progressive tumors were enrolled and treated with 3 escalating doses of 100, 400 and 800 µg. 15 pts experienced stable disease according to RECIST. For 11 of them, the treatment was extended, up to 9 months. INVAC-1 was well tolerated with no dose-limiting toxicities. No significant biological signs of autoimmunity were observed. No significant modification in inflammatory plasma cytokines levels was observed after INVAC-1 administration. INVAC-1 triggered de novo or enhanced pre-existing CD4/CD8 specific anti-hTERT response in 63% of pts. This specific anti-hTERT immune response was enhanced ex vivo by adding the immune checkpoint inhibitor nivolumab. ctDNA was evaluated in 17 pts. We observed a ctDNA decrease in 6 cases, a stable level in 5 cases and an increase in 6 cases. Conclusions: Results indicate that INVAC-1 was well tolerated and immunogenic at the doses and schedule tested. Disease stabilization was obtained for the majority of pts (58%) according to RECIST criteria or ctDNA levels. Clinical trial information: NCT02301754.

670 Background: MSI-H tumors have shown to be responsive to PD-1 inhibitor therapy. We evaluated the anti-PD-L1 mAb durvalumab in patients with MSI-H tumors, in two ongoing studies: a phase 1/2, multicenter, open-label study in patients with advanced solid tumors, and a phase 2 single-center study in patients with advanced colorectal cancer (CRC). Methods: Patients with MSI-H tumors (determined locally by immunohistochemistry or sequencing) received durvalumab 10 mg/kg IV every 2 weeks for 12 months or until confirmed progressive disease, whichever was first. Objectives were to evaluate safety and antitumor activity (per investigator-assessed RECIST v1.1). Results: As of Oct 16, 2017, 62 MSI-H patients (97% with prior anti-cancer therapy) received treatment in the multicenter study; median duration of follow-up was 29 months. Treatment-related adverse events (TRAEs) occurred in 37 patients (60%), most commonly diarrhea (15%), asthenia (11%), fatigue (11%), nausea (10%), and hypothyroidism (10%). Grade 3/4 TRAEs occurred in 2 patients (3%). There were no deaths or treatment discontinuations due to TRAEs. Objective response rates (ORR) were 23% for the total population and 22% for patients with CRC; 9 of 14 responders were ongoing at data cutoff. As of Sep 13, 2018, 11 patients with MSI-H CRC were treated in the single-center study; median duration of follow-up was 30 months. One patient discontinued treatment due to treatment-related aseptic meningitis (resolved with steroids); response rate and survival were similar to the multicenter study (Table). Conclusions: Durvalumab had a tolerable safety profile, and showed promising antitumor activity and overall survival in patients with MSI-H tumors. Clinical trial information: NCT01693562 and NCT02227667. [Table: see text]

Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox’s proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54–142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10–14). Median overall survival was 73 months (95% CI 61–86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78–204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36–11.92; p

Castration-resistant prostate cancer was subjected to a paradigm switch from hormone resistance to androgen deprivation therapy resistance during the last decade. Indeed, new therapeutics targeting the androgen receptor showed clinical efficacy in patients with progressive disease under castration. Thus, it is a proof that the AR remains a dominant driver of oncogenesis in earlier-called hormone resistant prostate cancer. This review summarizes the molecular mechanisms involved in castration-resistant prostate cancer.