Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (NCT03921671)

被引：10

作者：

Proto, C. ^{[1
]}

Ganzinelli, M. ^{[1
]}

Manglaviti, S. ^{[1
]}

Imbimbo, M. ^{[1
,2
]}

Galli, G. ^{[1
,16
]}

Marabese, M. ^{[3
]}

Zollo, F. ^{[4
]}

Alvisi, M. F. ^{[4
]}

Perrino, M. ^{[5
]}

Cordua, N. ^{[5
]}

Borea, F. ^{[6
]}

de Vincenzo, F. ^{[5
]}

Chella, A. ^{[7
]}

Cappelli, S. ^{[7
]}

Pardini, E. ^{[7
]}

Ballatore, Z. ^{[8
]}

Lucarelli, A. ^{[8
]}

Ambrosini, E. ^{[9
]}

Giuliano, M. ^{[10
,11
]}

Pietroluongo, E. ^{[10
]}

Mulargiu, C. ^{[12
]}

Fabbri, A. ^{[13
]}

Prelaj, A. ^{[1
]}

Occhipinti, M. ^{[1
]}

Brambilla, M. ^{[1
]}

Mazzeo, L. ^{[1
]}

Beninato, T. ^{[1
]}

Vigorito, R. ^{[14
]}

Ruggirello, M. ^{[14
]}

Greco, F. G. ^{[14
]}

Calareso, G. ^{[14
]}

Miliziano, D. ^{[1
]}

Rulli, E. ^{[4
]}

De Simone, I. ^{[4
]}

Torri, V. ^{[4
]}

de Braud, F. G. M. ^{[1
,15
]}

Pasello, G. ^{[12
,16
]}

De Placido, P.

Berardi, R. ^{[9
]}

Petrini, I. ^{[17
]}

Zucali, P. ^{[5
,6
]}

Garassino, M. C. ^{[1
,18
]}

Lo Russo, G. ^{[1
]}

机构：

[1] Fdn IRCCS Ist Nazl Tumori, Med Oncol Dept, Milan, Italy

[2] EOC, Oncol Inst Southern Switzerland, Bellinzona, Switzerland

[3] Ist Ric Farmacolog Mario Negri IRCCS, Lab Mol Pharmacol, Milan, Italy

[4] Ist Ric Farmacolog Mario Negri IRCCS, Methodol Clin Res Lab, Milan, Italy

[5] IRCCS Humanitas Res Hosp, Dept Oncol, Milan, Italy

[6] Humanitas Univ, Dept Biomed Sci, Milan, Italy

[7] Azienda Osped Univ Pisana, Pneumol Unit, Pisa, Italy

[8] Azienda Osped Univ Marche, Dept Med Oncol, Ancona, Italy

[9] Univ Politecn Marche, Dept Clin & Mol Sci, Ancona, Italy

[10] Univ Federico II, Dept Clin Med & Surg, Naples, Italy

[11] Rare Tumors Coordinating Ctr Campania Reg CRCTR, Naples, Italy

[12] Ist Oncol Venetod IRCCS, Med Oncol 2, Padua, Italy

[13] Fdn IRCCS Ist Nazl Tumori, Dept Pathol, Milan, Italy

[14] Fdn IRCCS Ist Nazl Tumori, Dept Intervent Radiol, Milan, Italy

[15] Univ Milan, Dept Oncol & Hemato Oncol, Milan, Italy

[16] Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy

[17] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Med Oncol, Pisa, Italy

[18] Univ Chicago, Dept Med, Thorac Oncol Program, Sect Hematol Oncol, Chicago, IL USA

来源：

ANNALS OF ONCOLOGY | 2024年 / 35卷 / 09期

关键词：

thymic carcinoma; ramucirumab; antiangiogenics; fi rst line; chemotherapy; EPITHELIAL TUMORS; OPEN-LABEL; CHEMOTHERAPY; MALIGNANCIES; MULTICENTER; SUNITINIB; CISPLATIN; THERAPY; THYMOMA;

D O I：

10.1016/j.annonc.2024.06.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. The RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC. Patients and methods: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment-na & iuml;ve advanced TC. They received ramucirumab, carboplatin and paclitaxel for six cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Centralized radiologic review was carried out. Results: From November 2018 to June 2023, 52 patients were screened and 35 were enrolled. Median age was 60.8 performance status was 0 in 68.5% and 1 in 31.4% of patients. At the present analysis carried out some months after the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95% confidence interval (CI) 63.1% to 91.6%]. At the centralized radiological review of 33/35 assessable patients, ORR was 57.6% (95% CI 39.2% to 74.5%). After a median follow-up of 31.6 months, median PFS was 18.1 months (95% CI 10.8-52.3 months) and median OS was 43.8 months (95% CI 31.9 months-not reached). Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE >= grade 3. Conclusions: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC.

引用

页码：817 / 826

页数：10

共 50 条

[41] Phase II Trial of Sunitinib in Patients with Type B3 Thymoma or Thymic Carcinoma in Second and Further Lines - STYLE Trial (NCT03449173) [J].

Proto, C. ;

Galli, G. ;

Manglaviti, S. ;

Lo Russo, G. ;

Ganzinelli, M. ;

Galli, F. ;

Musca, M. ;

Rulli, E. ;

Di Mauro, R. ;

Mella, G. ;

Lucarelli, A. ;

Paggio, A. ;

Valleggi, S. ;

Ballatore, Z. ;

Dal Maso, A. ;

Perrino, M. ;

Chella, A. ;

Sbrana, A. ;

Prelaj, A. ;

Ferrara, R. ;

Occhipinti, M. ;

Brambilla, M. ;

De Toma, A. ;

Mazzeo, L. ;

Beninato, T. ;

Pircher, C. ;

De Braud, F. ;

Pasello, G. ;

Petrini, I. ;

Berardi, R. ;

Garassino, M. ;

Zucali, P. .

JOURNAL OF THORACIC ONCOLOGY, 2022, 17 (09) :S79-S80

[42] Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial [J].

Yardley, Denise A. ;

Brufsky, Adam ;

Coleman, Robert E. ;

Conte, Pierfranco F. ;

Cortes, Javier ;

Glueck, Stefan ;

Nabholtz, Jean-Mark A. ;

O'Shaughnessy, Joyce ;

Beck, Robert M. ;

Ko, Amy ;

Renschler, Markus F. ;

Barton, Debora ;

Harbeck, Nadia .

TRIALS, 2015, 16

[43] Safety and efficacy of paclitaxel plus carboplatin versus paclitaxel plus cisplatin in neoadjuvant chemoradiotherapy for patients with locally advanced esophageal carcinoma: a retrospective study [J].

Li Jiang ;

Jie Zhu ;

Xue Chen ;

Yi Wang ;

Lei Wu ;

Gang Wan ;

Yongtao Han ;

Xuefeng Leng ;

Lin Peng ;

Qifeng Wang .

Radiation Oncology, 17

[44] The efficacy and safety of albumin-bound paclitaxel plus carboplatin as neoadjuvant therapy for potentially resectable lung squamous cell carcinoma: a real-world retrospective cohort study [J].

Jiang, Wenjuan ;

Zhou, Yuling ;

Zeng, Liang ;

Xiong, Yi ;

Liu, Li ;

Zhou, Chunhua ;

Yang, Haiyan ;

Guo, Hui ;

Minervini, Fabrizio ;

Bongiolatti, Stefano ;

Yang, Nong ;

Zhang, Yongchang ;

Tao, Min .

TRANSLATIONAL LUNG CANCER RESEARCH, 2022, 11 (04) :647-655

[45] Phase II trial of paclitaxel-carboplatin with intercalated gefitinib for untreated, epidermal growth factor receptor gene mutation status unknown non-small cell lung cancer [J].

Yang, Jianliang ;

Shi, Yuankai ;

Zhang, Xiangru ;

Xu, Jianping ;

Wang, Bin ;

Hao, Xuezhi ;

Li, Junling ;

Yan, Wang .

THORACIC CANCER, 2014, 5 (02) :149-154

[46] Randomized Phase II Study of Bevacizumab in Combination With Carboplatin Plus Paclitaxel in Patients With Previously Untreated Advanced Mucosal Melanoma [J].

Yan, Xieqiao ;

Sheng, Xinan ;

Chi, Zhihong ;

Si, Lu ;

Cui, Chuanliang ;

Kong, Yan ;

Tang, Bixia ;

Mao, Lili ;

Wang, Xuan ;

Lian, Bin ;

Li, Siming ;

Bai, Xue ;

Zhou, Li ;

Dai, Jie ;

Yao, Hong ;

Guo, Jun .

JOURNAL OF CLINICAL ONCOLOGY, 2021, 39 (08) :881-+

[47] Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial [J].

Huebner, G. ;

Link, H. ;

Kohne, C. H. ;

Stahl, M. ;

Kretzschmar, A. ;

Steinbach, S. ;

Folprecht, G. ;

Bernhard, H. ;

Al-Batran, S. E. ;

Schoffski, P. ;

Burkart, C. ;

Kullmann, F. ;

Otremba, B. ;

Menges, M. ;

Hoffmann, M. ;

Kaiser, U. ;

Aldaoud, A. ;

Jahn, A. .

BRITISH JOURNAL OF CANCER, 2009, 100 (01) :44-49

[48] Durvalumab Plus Olaparib in Previously Untreated, Platinum-Ineligible Patients With Metastatic Urothelial Carcinoma: A Multicenter, Randomized, Phase II Trial (BAYOU) [J].

Rosenberg, Jonathan E. ;

Park, Se Hoon ;

Kozlov, Vadim ;

Dao, Tu V. ;

Castellano, Daniel ;

Li, Jian-Ri ;

Mukherjee, Som D. ;

Howells, Kathryn ;

Dry, Hannah ;

Lanasa, Mark C. ;

Stewart, Ross ;

Bajorin, Dean F. .

JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 (01) :43-+

[49] Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer [J].

F Cappuzzo ;

F Mazzoni ;

A Gennari ;

S Donati ;

B Salvadori ;

C Orlandini ;

G L Cetto ;

A Molino ;

E Galligioni ;

M Mansutti ;

S Tumolo ;

A Lucentini ;

F Valduga ;

S Bartolini ;

L Crinò ;

P F Conte .

British Journal of Cancer, 2004, 90 :31-35

[50] Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer [J].

Cappuzzo, F ;

Mazzoni, F ;

Gennari, A ;

Donati, S ;

Salvadori, B ;

Orlandini, C ;

Cetto, GL ;

Molino, A ;

Galligioni, E ;

Mansutti, M ;

Tumolo, S ;

Lucentini, A ;

Valduga, F ;

Bartolini, S ;

Crinò, L ;

Conte, PF .

BRITISH JOURNAL OF CANCER, 2004, 90 (01) :31-35

← 1 2 3 4 5 →