Second-line treatment and prognostic factors in neuroendocrine carcinoma: the RBNEC study

in Endocrine-Related Cancer
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  • 1 Oncologie Endocrinienne, Département d’Imagerie, Gustave Roussy, Villejuif, France
  • | 2 Service d’Oncologie, ENETS Centre of Excellence, Hospices Civils de Lyon et Université de Lyon, Lyon, France
  • | 3 Service de Pathologie, Département de Biologie et Pathologie Médicale, Gustave Roussy, Villejuif, France
  • | 4 Département d’Oncologie, Institut Curie, Paris, France
  • | 5 Service d’Hépato-gastro-entérologie et Cancérologie Digestive, CHU Amiens Picardie, Amiens, France
  • | 6 Département d’Hépato-gastro-entérologie, CHU de Reims, Reims, France
  • | 7 Service d'Endocrinologie, Diabétologie et Maladies Métaboliques, CHU Clermont-Ferrand, Clermont-Ferrand, France
  • | 8 Laboratoire GReD, Université Clermont Auvergne, Clermont-Ferrand, France
  • | 9 Département d’Endocrinologie-Diabétologie-Nutrition, CHU d’Angers, Angers Cedex 9, France
  • | 10 CHU de Lille, Service d’Endocrinologie, Lille, France
  • | 11 CHU Clermont-Ferrand, Service de Chirurgie Digestive et Hépatobiliaire, Clermont-Ferrand, France
  • | 12 CRB, CHU d’Angers, Angers Cedex 9, France
  • | 13 Département de Chirurgie, Gustave Roussy, Villejuif, France
  • | 14 CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, Université de Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277, Lille, France
  • | 15 Département de Pathologie, CHU d’Angers, Angers Cedex 9, France
  • | 16 Laboratoire d’Anatomie Pathologique, CHU Clermont-Ferrand, Clermont-Ferrand, France
  • | 17 Service d’Anatomo-Pathologie, CHU Reims, Reims, France
  • | 18 Service d’Anatomo-Pathologie, CHU Amiens, Amiens, France
  • | 19 Service d’Anatomo-Pathologie, Institut Curie, Paris, France
  • | 20 Service d’Anatomo-Pathologie, ENETS Centre of Excellence, Hospices Civils de Lyon et Université de Lyon, Lyon, France
  • | 21 Service d’Oncologie Digestive, Département de Médecine, Gustave Roussy, Villejuif, France
  • | 22 Faculté de Médecine, Université Paris Saclay, Le Kremlin-Bicêtre, France

Contributor Notes

Correspondence should be addressed to J Hadoux: Julien.hadoux@gustaveroussy.fr

*(J-Y Scoazec and E Baudin contributed equally to this work)

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Neuroendocrine carcinomas (NEC) are aggressive malignant diseases. Etoposide-based rechallenge (EBR) and the prognostic role of RB transcriptional corepressor 1 (RB1) status in second-line chemotherapy (2L) have not been studied. The objectives of this study were to report the results of 2L including EBR as well as prognostic factors in a national retrospective multicentre study. NEC patients treated with 2L and further, with tissue samples available, were included. RB1 status and morphological classification were reviewed centrally. Among the 121 NEC patients (40% female, median age 61 years) included, there were 73 small-cell NEC (60%), 34 large-cell NEC (28%) and 14 NEC (not otherwise specified, 12%). Primary sites were lung (39%), gastroenteropancreatic (36%), other (13%) and unknown (12%). Median Ki-67 index was 80%. Median progression-free survival (PFS) and overall survival (OS) under 2L were 2.1 and 6.2 months, respectively. No difference was observed between patients who received an ‘adenocarcinoma-like’ or a ‘neuroendocrine-like’ 2L or according to the RB1 status. Thoracic NEC primary was the only adverse prognostic factor for OS. EBR, administered to 31 patients, resulted in a 62% disease control rate with a median PFS and OS of 3.2 and 11.7 months, respectively. In the 94 patients with a relapse-free interval of ≥3 months after first-line platinum–etoposide chemotherapy, the median OS was 12 months in patients who received EBR as compared to 5.9 months in patients who did not (P = 0.043). EBR could be the best 2L option for patient with initial response to first-line platinum–etoposide lasting at least 3 months. RB1 status does not provide prognostic information in this setting.

 

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  • de Mestier L, Lepage C, Baudin E, Coriat R, Courbon F, Couvelard A, Do Cao C, Frampas E, Gaujoux S, Gincul R, et al.2020 Digestive Neuroendocrine Neoplasms (NEN): French Intergroup clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, GTE, RENATEN, TENPATH, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR). Digestive and Liver Disease 52 473492. (https://doi.org/10.1016/j.dld.2020.02.011)

    • Search Google Scholar
    • Export Citation
  • Derks JL, Leblay N, Thunnissen E, van Suylen RJ, den Bakker M, Groen HJM, Smit EF, Damhuis R, van den Broek EC, Charbrier A, et al.2018 Molecular subtypes of pulmonary large-cell neuroendocrine carcinoma predict chemotherapy treatment outcome. Clinical Cancer Research 24 3342. (https://doi.org/10.1158/1078-0432.CCR-17-1921)

    • Search Google Scholar
    • Export Citation
  • Eisenhauer EA, Vermorken JB & van Glabbeke M 1997 Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer: a multivariate analysis of 704 patients. Annals of Oncology 8 963968. (https://doi.org/10.1023/a:1008240421028)

    • Search Google Scholar
    • Export Citation
  • Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al.2009 New Response Evaluation Criteria in Solid Tumours: Revised RECIST Guideline, version 1.1. European Journal of Cancer 45 228247. (https://doi.org/10.1016/j.ejca.2008.10.026)

    • Search Google Scholar
    • Export Citation
  • Elvebakken H, Perren A, Scoazec JY, Tang LH, Federspiel B, Klimstra DS, Vestermark LW, Ali AS, Zlobec I, Myklebust , et al.2021 A consensus developed morphological re-evaluation of 196 high-grade gastroenteropancreatic neuroendocrine neoplasms and its clinical correlations. Neuroendocrinology 111 883894. (https://doi.org/10.1159/000511905)

    • Search Google Scholar
    • Export Citation
  • Garassino MC, Torri V, Michetti G, Lo Dico M, La Verde N, Aglione S, Mancuso A, Gallerani E, Galetta D, Martelli O, et al.2011 Outcomes of small-cell lung cancer patients treated with second-line chemotherapy: a multi-institutional retrospective analysis. Lung Cancer 72 378383. (https://doi.org/10.1016/j.lungcan.2010.09.009)

    • Search Google Scholar
    • Export Citation
  • Garcia-Carbonero R, Sorbye H, Baudin E, Raymond E, Wiedenmann B, Niederle B, Sedlackova E, Toumpanakis C, Anlauf M, Cwikla JB, et al.2016 Enets consensus guidelines for high-grade gastroenteropancreatic neuroendocrine tumors and neuroendocrine carcinomas. Neuroendocrinology 103 186194. (https://doi.org/10.1159/000443172)

    • Search Google Scholar
    • Export Citation
  • Genestreti G, Tiseo M, Kenmotsu H, Kazushige W, Di Battista M, Cavallo G, Carloni F, Bongiovanni A, Burgio MA, Casanova C, et al.2015 Outcomes of platinum-sensitive small-cell lung cancer patients treated With platinum/etoposide rechallenge: a multi-institutional retrospective analysis. Clinical Lung Cancer 16 e223e228. (https://doi.org/10.1016/j.cllc.2015.04.006)

    • Search Google Scholar
    • Export Citation
  • George J, Walter V, Peifer M, Alexandrov LB, Seidel D, Leenders F, Maas L, Müller C, Dahmen I, Delhomme TM, et al.2018 Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nature Communications 9 1048. (https://doi.org/10.1038/s41467-018-03099-x)

    • Search Google Scholar
    • Export Citation
  • Giaccone G, Donadio M, Bonardi G, Testore F & Calciati A 1988 Teniposide in the treatment of small-cell lung cancer: the influence of prior chemotherapy. Journal of Clinical Oncology 6 12641270. (https://doi.org/10.1200/JCO.1988.6.8.1264)

    • Search Google Scholar
    • Export Citation
  • Hadoux J, Kanaan C, Durand A, Hescot S, Hautefeuille V, Cadiot G, Tauveron I, Laboureau S, Cao CD, Walter T, et al.2021a Prognostic factors of metastatic neuroendocrine carcinoma under first-line treatment with platinum etoposide with a focus on NEC score and Rb expression: results from the multicentre RBNEC study of the Groupe d’Etude des Tumeurs Endocrines (GTE) and the ENDOCAN-RENATEN network. European Journal of Cancer 152 100115. (https://doi.org/10.1016/j.ejca.2021.04.030)

    • Search Google Scholar
    • Export Citation
  • Hadoux J, Afchain P, Walter T, Tougeron D, Hautefeuille V, Monterymard C, Lorgis V, Thuillier F, Baudin E, Scoazec JY, et al.2021b FOLFIRINEC: a randomized phase II trial of mFOLFIRINOX vs platinum-etoposide for metastatic neuroendocrine carcinoma of gastroenteropancreatic or unknown origin. Digestive and Liver Disease 53 824829. (https://doi.org/10.1016/j.dld.2021.04.016)

    • Search Google Scholar
    • Export Citation
  • Hadoux J, Malka D, Planchard D, Scoazec JY, Caramella C, Guigay J, Boige V, Leboulleux S, Burtin P, Berdelou A, et al.2015 Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma. Endocrine-Related Cancer 22 289298. (https://doi.org/10.1530/ERC-15-0075)

    • Search Google Scholar
    • Export Citation
  • Hentic O, Hammel P, Couvelard A, Rebours V, Zappa M, Palazzo M, Maire F, Goujon G, Gillet A, Lévy P, et al.2012 FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3. Endocrine-Related Cancer 19 751757. (https://doi.org/10.1530/ERC-12-0002)

    • Search Google Scholar
    • Export Citation
  • Klimstra D, Kloppel G, La Rosa S & Rindi G 2019 Classification of Neuroendocrine Neoplasms of the Digestive System. Lyon, France: International Agency for Research on Cancer

    • Search Google Scholar
    • Export Citation
  • Lara PN, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, et al.2009 Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. Journal of Clinical Oncology 27 25302535. (https://doi.org/10.1200/JCO.2008.20.1061)

    • Search Google Scholar
    • Export Citation
  • Le Treut J, Sault MC, Lena H, Souquet PJ, Vergnenegre A, Le Caer H, Berard H, Boffa S, Monnet I, Damotte D, et al.2013 Multicentre phase II study of cisplatin-etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study. Annals of Oncology 24 15481552. (https://doi.org/10.1093/annonc/mdt009)

    • Search Google Scholar
    • Export Citation
  • Pavel M, Öberg K, Falconi M, Krenning EP, Sundin A, Perren A, Berruti A & ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org 2020 Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 31 844860. (https://doi.org/10.1016/j.annonc.2020.03.304)

    • Search Google Scholar
    • Export Citation
  • Rekhtman N, Pietanza MC, Hellmann MD, Naidoo J, Arora A, Won H, Halpenny DF, Wang H, Tian SK, Litvak AM, et al.2016 Next-generation sequencing of pulmonary large cell neuroendocrine carcinoma reveals small cell carcinoma-like and non-small cell carcinoma-like subsets. Clinical Cancer Research 22 36183629. (https://doi.org/10.1158/1078-0432.CCR-15-2946)

    • Search Google Scholar
    • Export Citation
  • Rindi G, Klimstra DS, Abedi-Ardekani B, Asa SL, Bosman FT, Brambilla E, Busam KJ, de Krijger RR, Dietel M, El-Naggar AK, et al.2018 A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Modern Pathology 31 17701786. (https://doi.org/10.1038/s41379-018-0110-y)

    • Search Google Scholar
    • Export Citation
  • Rindi G, Mete O, Uccella S, Basturk O, La Rosa S, Brosens LAA, Ezzat S, de Herder WW, Klimstra DS, Papotti M, et al.2022 Overview of the 2022 WHO classification of neuroendocrine neoplasms. Endocrine Pathology 33 115154. (https://doi.org/10.1007/s12022-022-09708-2)

    • Search Google Scholar
    • Export Citation
  • Shiozawa T, Sekine I, Aida Y, Watanabe H, Nakazawa K, Kurishima K, Satoh H & Hizawa N 2018 Rechallenge with first-line platinum chemotherapy for sensitive-relapsed small-cell lung cancer. Case Reports in Oncology 11 622632. (https://doi.org/10.1159/000492780)

    • Search Google Scholar
    • Export Citation
  • Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, Dueland S, Hofsli E, Guren MG, Ohrling K, et al.2013 Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the Nordic NEC study. Annals of Oncology 24 152160. (https://doi.org/10.1093/annonc/mds276)

    • Search Google Scholar
    • Export Citation
  • Takizawa N, Ohishi Y, Hirahashi M, Takahashi S, Nakamura K, Tanaka M, Oki E, Takayanagi R & Oda Y 2015 Molecular characteristics of colorectal neuroendocrine carcinoma; similarities with adenocarcinoma rather than neuroendocrine tumor. Human Pathology 46 18901900. (https://doi.org/10.1016/j.humpath.2015.08.006)

    • Search Google Scholar
    • Export Citation
  • Walter T, Tougeron D, Baudin E, Le Malicot K, Lecomte T, Malka D, Hentic O, Manfredi S, Bonnet I, Guimbaud R, et al.2017 Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: are they really heterogeneous? Insights from the FFCD-GTE national cohort. European Journal of Cancer 79 158165. (https://doi.org/10.1016/j.ejca.2017.04.009)

    • Search Google Scholar
    • Export Citation
  • Yachida S, Vakiani E, White CM, Zhong Y, Saunders T, Morgan R, de Wilde RF, Maitra A, Hicks J, Demarzo AM, et al.2012 Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors. American Journal of Surgical Pathology 36 173184. (https://doi.org/10.1097/PAS.0b013e3182417d36)

    • Search Google Scholar
    • Export Citation