Search

Background: Cabozantinib is an approved therapy for advanced RCC (in the USA) and in treatment-naive patients with intermediate/poor risk, as well as following VEGF-targeted therapy (in Europe) Trial design: CaboPoint (NCT03945773) is a phase II, open-label study of cabozantinib in adults with unresectable, locally advanced or metastatic clear-cell RCC, whose disease progressed after checkpoint inhibitor therapy with ipilimumab and nivolumab alone (cohort A) or in combination with VEGF-targeted therapy (cohort B) The primary endpoint is objective response rate Secondary endpoints include time to response, duration of response, disease control rate, progression-free survival and overall survival A target of 250 patients at 50 European sites will receive cabozantinib (60 mg once daily;self-administered at home) for ≤ 18 months after the last patient receives their first dose Safety assessments will occur every 2 weeks up to week 4, then every 4 weeks Patients may continue cabozantinib after disease progression if there is clinical benefit During follow-up, patients who discontinue early will be contacted every 12 weeks to assess survival and subsequent therapy Each cohort will have an interim analysis when 60% of patients reach 12 months of follow-up CaboPoint has been adjusted to allow the trial to continue during the COVID-19 outbreak, protecting participants in compliance with the study protocol 1 Alternative arrangements include: study drug dispensation to the participant’s home if they cannot attend the study site;safety assessments at the study site or remotely at a local health care provider, within the protocol defined window;tumour assessments at a local radiology facility if they cannot attend the study site Enrolment is permitted if the patient can be managed in compliance with the protocol and alternative arrangements 1 The limitations, risks and impact on data privacy of such arrangements will be accounted for and documented Clinical trial identification: NCT03945773 Editorial acknowledgement: Dr Tamzin Gristwood of Oxford PharmaGenesis, Oxford, UK, provided medical writing and editorial support, which was sponsored by Ipsen, in accordance with Good Publication Practice guidelines Legal entity responsible for the study: Ipsen Funding: Ipsen Disclosure: L Albiges: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Advisory/Consultancy, Travel/Accommodation/Expenses: MSD;Advisory/Consultancy: Novartis;Advisory/Consultancy: Amgen;Advisory/Consultancy: Ipsen;Advisory/Consultancy: Roche;Advisory/Consultancy: Pfizer;Advisory/Consultancy: Merck;Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Exelixis;Advisory/Consultancy: Peloton Therapeutics;Advisory/Consultancy: Corvus Pharmaceuticals M Schmidinger: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy: Novartis;Honoraria (self), Advisory/Consultancy: BMS;Honoraria (self), Advisory/Consultancy: MSD;Honoraria (self), Advisory/Consultancy: Merck;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: EUSA;Honoraria (self), Advisory/Consultancy: Ipsen;Honoraria (self), Advisory/Consultancy: Exelixis;Honoraria (self), Advisory/Consultancy: EISAI;Honoraria (self), Advisory/Consultancy: Alkermes N Taguieva-Pioger: Full/Part-time employment: Ipsen D Perol: Honoraria (self): Roche;Honoraria (self): BMS;Honoraria (self): MSD;Honoraria (self): Ipsen;Honoraria (self): Pierre Fabre;Honoraria (self): Novartis;Honoraria (self): Takeda;Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca;Research grant/Funding (institution): MSD Avenir V Gruenwald: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options: AstraZeneca;Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock opt ons: BMS;Honoraria (self), Research grant/Funding (institution), Shareholder/Stockholder/Stock options: MSD;Honoraria (self): Roche;Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Ipsen;Honoraria (self), Travel/Accommodation/Expenses: Bayer;Honoraria (self): Merck Serono;Honoraria (self): Janssen-Cilag;Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Honoraria (self): Lilly;Honoraria (self): PharmaMar;Honoraria (self), Research grant/Funding (institution): Novartis;Honoraria (self): EUSAPharm;Honoraria (self): Eisai

Background In the evolution of metastatic castration-resistant prostate cancer (mCRPC), patients present visceral metastases with or without neuroendocrine differentiation in 20% of cases. Patients and methods We assessed the efficacy and toxicity of a platinum-based chemotherapy regimen in mCRPC patients with either neuroendocrine differentiation defined by high serum levels of chromogranin A (CgA) and neuron-specific enolase (NSE) or visceral metastases. Patients received the combination of carboplatin and etoposide every 3 weeks. Efficacy end points included prostate-specific antigen (PSA) and neuroendocrine marker response, objective response and toxicity. Results Of the 60 patients included from April 2005 to January 2008, 78.6% had bone metastases, 46.4% had lymph node involvement and 57.1% had liver and/or lung localizations. The objective response rate was 8.9% in the 46 patients with measurable disease. A neuroendocrine response was observed in 31% of cases for NSE and 7% for CgA. The PSA response rate was 8%. The most common grade 3–4 treatment-related toxic effects were neutropenia (65.5%), thrombocytopenia (32.7%) and anemia (27.3%). There was 7.2% febrile neutropenia, with one toxicity-related death. The median follow-up was 9.3 months [95% confidence interval (CI) 0.2–27.1] and the median overall survival 9.6 months (95% CI 8.7–12.7). Conclusion The benefit–risk ratio of this regimen seems unfavorable due to poor response and high toxicity.

Background:Imatinib evaluated as a new treatment option in patients with recurrent or established progressive aggressive fibromatosis/desmoid tumor (AF/DT). Patients and methods:Forty patients with unresectable and progressive symptomatic AF/DT were treated with imatinib (400 mg/day for 1 year) in a Simon’s optimal two-stage phase II study (P 0 =10%,P 1 =30%,a=5%, b=10%). The primary end point was non-progressive at 3 months (RECIST). Results:The study population consisted of 28 women and 12 men, with a mean age of 41 (range 20‐72 years). Most of the primary sites were extra-abdominal (24, 54.5%). Familial adenomatous polyposis was observed in six (15%) cases. The median follow-up was 34 months. Imatinib toxicity was similar to that previously reported in literature. Tumor assessment was validated by a central independent radiology committee for 35 patients At 3 months, one (3%) complete and three (9%) partial confirmed responses were observed. The non-progression rates at 3, 6 and 12 months were, respectively, 91%, 80% and 67%. The 2-year progression-free and overall survival rates were 55% and 95%, respectively. Two patients with mesenteric AF/DT died from progressive disease. Conclusion:Imatinib is active in the treatment of recurrent and progressive AF/DT, providing objective response and long-term stable disease in a large proportion of patients.

Background: This prospective multicentric phase II study aimed to confirm the results of the C5R protocol of high-dose methotrexate (MTX)-based chemotherapy (CT) for immunocompetent primary central nervous system lymphoma. Patients and methods: A total of 99 patients received age-adapted CT (C5R protocol) followed by radiotherapy. Patients younger than 61 years (group 1, n = 45) received the full C5R with MTX, doxorubicin, vincristine, cyclophosphamide, and cytarabine. Patients aged 61-70 years (group 2, n = 36) received reduced doses. Patients older than 70 years (group 3, n = 18) received four courses of MTX, cyclophosphamide, and etoposide. Results: Median age was 63 years and 51% of patients had performance status of more than one. Seventeen patients died of toxicity during CT. Complete response was achieved in 56%, 53%, and 28% of patients in groups 1, 2, and 3, respectively. With a median follow-up of 83 months, the 5-year progression-free survival was 31%, 28%, and 11% and the 5-year overall survival 42%, 31%, and 17% for groups 1, 2, and 3, respectively. Leukoencephalopathy occurred in 32% of assessable patients, in both group 1 and groups 2-3. Conclusion: The C5R protocol was feasible in the multicentric setting with favorable long-term survival in patients younger than 60 years. Despite dose adaptation, results in older patients were disappointing.

Rationale The IFCT–GFPC 0502 phase III reported prolongation of progression-free survival with maintenance with either gemcitabine or erlotinib versus observation after cisplatin-gemcitabine chemotherapy in advanced NSCLC. Their incremental cost-effectiveness ratio (ICER) was assessed in global population and in pre specified sub-groups. Methods A cost-utility analysis was performed to evaluate ICER of maintenance therapy with either gemcitabine or erlotinib, compared to observation. Direct medical costs (drugs costs, hospitalization, examinations, second-line treatments and palliative costs) were prospectively collected per patient alongside the trial, until death, from the third party payer perspective. Utility were extracted from literature. Sensitivity analyses were performed. Results ICER for maintenance therapy with gemcitabine and erlotinib were respectively 76 625 and 184 733 €/quality-adjusted life years (QALY). Gemcitabine maintenance therapy had favourable ICER in patients with PS = 0 (52 213 €/QALY), in responders to induction chemotherapy (64 296 €/QALY) and in patients with adenocarcinoma (62 292 €/QALY); erlotinib had favourable ICER if PS = 0 (94 908 €/QALY), in patients with adenocarcinoma (97 160 €/QALY) and objective response to induction (101,186 €/QALY), but it is not cost-effective in patients with PS = 1, other histology or if stable disease. Conclusion Gemcitabine and erlotinib maintenance therapy have acceptable ICER but with wide variation, function of histology, PS and response to the first line chemotherapy. Disclosure I. Borget: Honoraria from Roche for set up a class in health economy (no relation with the present study). M. Perol: consultant or advisory board with Roche, Lilly (myself) Honoraria from Lilly, Roche, Pfizer, Boehringer Ingelheim (myself) Research funding from Lilly, Roche (myself). D. Perol: Honoraria : Roche (myself). G. Zalcman: Honoraria from Lilly, Roche Research funding from Lilly, Roche. A. Vergnenegre: honoraria and research funding from Roche. C. Chouaid: Honoraria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffman la Roche, Astra Zeneka, Sanofi Aventis, Lilly, Novartis and Amgen Research funding from AstraZeneca, Lilly, Novartis and Amgen. All other authors have declared no conflicts of interest.