A randomized phase II trial of Captem or Folfiri as second-line therapy in neuroendocrine carcinomas

被引：6

作者：

Bongiovanni, Alberto ^{[2
]}

Liverani, Chiara ^{[1
]}

Foca, Flavia ^{[3
]}

Bergamo, Francesca ^{[4
]}

Leo, Silvana ^{[5
]}

Pusceddu, Sara ^{[6
]}

Gelsomino, Fabio ^{[7
]}

Brizzi, Maria Pia ^{[8
]}

Di Meglio, Giovanni ^{[9
]}

Spada, Francesca ^{[10
]}

Tamberi, Stefano ^{[11
]}

Lolli, Ivan ^{[12
]}

Cives, Mauro ^{[13
,14
]}

Marconcini, Riccardo ^{[15
]}

Pucci, Francesca ^{[16
]}

Berardi, Rossana ^{[17
]}

Antonuzzo, Lorenzo ^{[18
,19
]}

Badalamenti, Giuseppe ^{[20
]}

Santini, Daniele ^{[21
]}

Recine, Federica ^{[22
]}

Vanni, Silvia ^{[1
]}

Tebaldi, Michela ^{[3
]}

Severi, Stefano ^{[23
]}

Rudnas, Britt ^{[3
]}

Nanni, Oriana ^{[3
]}

Ranallo, Nicoletta ^{[2
]}

Crudi, Laura ^{[25
]}

Calabro, Luana ^{[24
,26
]}

Ibrahim, Toni ^{[2
,27
]}

机构：

[1] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Preclin & Osteoncol Unit, Biosci Lab, Via P Maroncelli 40, I- 47014 Meldola, Italy

[2] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Osteoncol & Rare Tumor Ctr CDO TR, Meldola, Italy

[3] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Unit Biostat & Clin Trials, Meldola, Italy

[4] IOV Veneto Inst Oncol IRCCS, Med Oncol Unit 1, Padua, Italy

[5] Vito Fazzi Hosp, Dept Med Oncol, Lecce, Italy

[6] Fdn IRCCS Ist Nazl Tumori, ENETS Ctr Excellence, Dept Med Oncol, Milan, Italy

[7] Univ Hosp Modena, Dept Oncol & Hematol, Div Oncol, Modena, Italy

[8] Univ Turin, San Luigi Gonzaga Univ Hosp, Dept Oncol, Orbassano, Italy

[9] Bolzano Hosp, Med Oncol Unit, Bolzano, Italy

[10] European Inst Oncol IEO IRCCS, Div Gastrointestinal Med Oncol & Neuroendocrine Tu, Milan, Italy

[11] Degli Infermi Hosp, Med Oncol Unit, Faenza, Italy

[12] Natl Inst Gastroenterol, Med Oncol Unit, IRCCS Saverio Bellis, Castellana Grotte, Italy

[13] Aldo Moro Univ Bari, Dept Interdisciplinary Med, Bari, Italy

[14] Azienda Osped Univ Consorziale Policlin Bari, Div Med Oncol, Bari, Italy

[15] Azienda Osped Univ Pisana, Med Oncol Unit, Pisa, Italy

[16] Univ Hosp Parma, Med Oncol Unit, Parma, Italy

[17] Univ Politecn Marche, Dept Med Oncol, Azienda Osped Univ Osped Riuniti Ancona, Ancona, Italy

[18] Careggi Univ Hosp, Clin Oncol Unit, Florence, Italy

[19] Univ Florence, Dept Expt & Clin Med, Florence, Italy

[20] Univ Palermo, Dept Surg Oncol & Oral Sci, Sect Med Oncol, Palermo, Italy

[21] Univ Campus Biomed, Dept Med Oncol, Rome, Italy

[22] Azienda Osped San Giovanni Addolorata, Med Oncol Unit, Rome, Italy

[23] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Nucl Med & Radiometab Units, Meldola, Italy

[24] IRCCS Ist Romagnolo Studio Tumori Dino Amadori, Oncol Pharm Unit, I-47014 Meldola, Italy

[25] Univ Hosp Ferrara, Dept Oncol, Cona, Italy

[26] Univ Ferrara, Dept Translat Med, Ferrara, Italy

[27] IRCCS Ist Ortoped Rizzoli, Osteoncol Bone & Soft Tissue Sarcomas & Innovat Th, Bologna, Italy

来源：

EUROPEAN JOURNAL OF CANCER | 2024年 / 208卷

关键词：

Neuroendocrine carcinomas (NECs); Phase II trial; Folfiri; Captem; Circulating miRNA; PROGNOSTIC-FACTORS; CHEMOTHERAPY; TUMORS; BIOMARKER; G3;

D O I：

10.1016/j.ejca.2024.114129

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Neuroendocrine Carcinomas (NECs) prognosis is poor.No standard second-line therapy is currently recognized after failure of platinum-based first-line treatment. FOLFIRI and CAPTEM regimens have shown promising activity in preliminary studies. We aimed to evaluate these regimens in metastatic NEC patients. Methods: This is an open-label, multicenter, randomized non-comparative phase II trial to evaluate the activity and safety of FOLFIRI or CAPTEM in metastatic NEC patients. Primary endpoints were the 12 weeks-Disease Control Rate (12w-DCR) by investigator assessment per RECIST v1.1 and safety per CTCAE v5.0. Additional endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Patients' serum samples were subject to NGS miRNome profiling in comparison with healthy donors to reveal differentially expressed miRNAs as candidate circulating biomarkers. Results: The study was halted for futility at interim analysis, as the minimum 12w-DCR threshold of 10 out of 25 patients required for the first step was not reached. From 06/03/2017 to 18/01/2021, 53 out of 112 patients were enrolled. Median follow-up was 22.6 months (range: 1.4-60.4). The 12w-DCR was 39.1 % in the FOLFIRI arm and 28.0 % in the CAPTEM arm. In the FOLFIRI subgroup the 12-months OS rate was 28.4 % (95 % CI: 12.7-46.5) while in the CAPTEM subgroup it was 32.4 % (95 % CI: 14.9-51.3). The most common G3-G4 side effects were neutropenia (n = 5, 18.5 %) and anemia (n = 2, 7.4 %) for FOLFIRI and G3-G4 thrombocytopenia (n = 2, 8.0 %), G4 nausea/vomiting (n = 1, 4.0 %) for CAPTEM. Three microRNAs emerged as NEC independent predictors. High expression values were found to be significantly associated with decreased PFS and OS. Conclusion: The safety profile of FOLFIRI and CAPTEM was manageable. FOLFIRI and CAPTEM chemotherapy showed comparable activity in the second-line setting after progression on etoposide/platinum. ClinicalTrials.gov identifier: NCT03387592

引用

页数：11

共 32 条

[1] First-line chemotherapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma [J].

Bongiovanni, Alberto ;

Riva, Nada ;

Ricci, Marianna ;

Liverani, Chiara ;

La Manna, Federico ;

De Vita, Alessandro ;

Foca, Flavia ;

Mercatali, Laura ;

Severi, Stefano ;

Amadori, Dino ;

Ibrahim, Toni .

ONCOTARGETS AND THERAPY, 2015, 8 :3613-3619

[2] Molecular Subtypes of Pulmonary Large-cell Neuroendocrine Carcinoma Predict Chemotherapy Treatment Outcome [J].

Derks, Jules L. ;

Leblay, Noemie ;

Thunnissen, Erik ;

Van Suylen, Robert Jan ;

den Bakker, Michael ;

Groen, Harry J. M. ;

Smit, Egbert F. ;

Damhuis, Ronald ;

van den Broek, Esther C. ;

Charbrier, Amelie ;

Foll, Matthieu ;

McKay, James D. ;

Fernandez-Cuesta, Lynnette ;

Speel, Ernst-Jan M. ;

Dingemans, Anne-Marie C. .

CLINICAL CANCER RESEARCH, 2018, 24 (01) :33-42

[3] MiRNA-3653 Is a Potential Tissue Biomarker for Increased Metastatic Risk in Pancreatic Neuroendocrine Tumours [J].

Gill, Preetjote ;

Kim, Edward ;

Chua, Terence C. ;

Clifton-Bligh, Roderick J. ;

Nahm, Christopher B. ;

Mittal, Anubhav ;

Gill, Anthony J. ;

Samra, Jaswinder S. .

ENDOCRINE PATHOLOGY, 2019, 30 (02) :128-133

[4] Prognostic relevance of proliferation-related miRNAs in pancreatic neuroendocrine neoplasms [J].

Grolmusz, Vince Kornel ;

Kovesdi, Annamaria ;

Borka, Katalin ;

Igaz, Peter ;

Patocs, Attila .

EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2018, 179 (04) :219-228

[5] Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma [J].

Hadoux, J. ;

Malka, D. ;

Planchard, D. ;

Scoazec, J. Y. ;

Caramella, C. ;

Guigay, J. ;

Boige, V. ;

Leboulleux, S. ;

Burtin, P. ;

Berdelou, A. ;

Loriot, Y. ;

Duvillard, P. ;

Chougnet, C. N. ;

Deandreis, D. ;

Schlumberger, M. ;

Borget, I. ;

Ducreux, M. ;

Baudin, E. .

[6] Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms [J].

Heetfeld, M. ;

Chougnet, C. N. ;

Olsen, I. H. ;

Rinke, A. ;

Borbath, I. ;

Crespo, G. ;

Barriuso, J. ;

Pavel, M. ;

O'Toole, D. ;

Walter, T. .

[7] FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3 [J].

Hentic, O. ;

Hammel, P. ;

Couvelard, A. ;

Rebours, V. ;

Zappa, M. ;

Palazzo, M. ;

Maire, F. ;

Goujon, G. ;

Gillet, A. ;

Levy, P. ;

Ruszniewski, P. .

[8] miR-320c regulates gemcitabine-resistance in pancreatic cancer via SMARCC1 [J].

Iwagami, Y. ;

Eguchi, H. ;

Nagano, H. ;

Akita, H. ;

Hama, N. ;

Wada, H. ;

Kawamoto, K. ;

Kobayashi, S. ;

Tomokuni, A. ;

Tomimaru, Y. ;

Mori, M. ;

Doki, Y. .

BRITISH JOURNAL OF CANCER, 2013, 109 (02) :502-511

[9] Tissue miR-200c-3p and circulating miR-1290 as potential prognostic biomarkers for colorectal cancer [J].

Kang, Enoch ;

Jung, Sung Cheol ;

Nam, Soo Kyung ;

Park, Yujun ;

Seo, Soo Hyun ;

Park, Kyoung Un ;

Oh, Heung-Kwon ;

Kim, Duck-Woo ;

Kang, Sung-Bum ;

Lee, Hye Seung .

SCIENTIFIC REPORTS, 2022, 12 (01)

[10] NONPARAMETRIC-ESTIMATION FROM INCOMPLETE OBSERVATIONS [J].

KAPLAN, EL ;

MEIER, P .

JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1958, 53 (282) :457-481

← 1 2 3 4 →