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01-04-2020 | Neutropenia | Research Article

First-line panitumumab plus docetaxel and cisplatin in advanced gastric and gastro-oesophageal junction adenocarcinoma: results of a phase II trial

Authors: G. Quintero Aldana, M. Salgado, S. Candamio, J. C. Méndez, M. Jorge, M. Reboredo, L. Vázquez Tuñas, C. Romero, M. Covela, A. Fernández Montes, M. Carmona, Y. Vidal Insua, R. López, the Galician Oncological Research Group (GGIO)

Published in: Clinical and Translational Oncology | Issue 4/2020

Abstract

Purpose

Panitumumab is extensively used for RAS-WT metastatic colorectal cancer. This study assessed the efficacy and safety of panitumumab plus first-line chemotherapy [docetaxel (DOC) and cisplatin (CIS)] in treatment-naïve advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma (ADC) patients.

Methods

Phase II, open-label, single-arm study includes treatment-naïve advanced gastric or GEJ-ADC patients from ten Spanish centres. Patients received panitumumab (6 mg/kg) plus DOC and CIS (50 mg/m² both) every 2 weeks until disease progression, unacceptable toxicity, or patient withdrawal. Primary endpoint: objective response rate (ORR); main secondary endpoints: disease control rate (DCR), duration of response (DoR), time to progressive disease (TTP), progression-free-survival (PFS), overall survival (OS), and safety.

Results

Forty-four patients were included; median age: 67.8 (range 43.3–82.7) years, 68.2% male. The ORR was 27.3% (95% CI 15.0, 42.8); median PFS and OS: 5.0 (95% CI 3.6, 6.9) and 7.2 (5.5, 9.0) months, respectively. Median TTP, DCR and DoR: 5.3 (range 3.8–7.0) months, 70.5% (95% CI 54.8, 83.2%), and 4.8 (1.8, NE) months. Median panitumumab treatment duration: 11.9 (range 0.1–34.9) weeks; 25.0% patients had a dose reduction and 40.9% discontinued treatment. Grade 3–4 adverse events (AEs): 68.2%/22.2% patients. Most common AEs: asthenia (75.0%) and mucosal inflammation (54.5%). Serious AEs were experienced by 54.6% patients; 9.1%, 13.6%, and 15.9% related to panitumumab, DOC, and CIS, respectively. Three (6.8%) patients died due to AEs not related to study treatment.

Conclusions

The addition of panitumumab to standard chemotherapy as the first-line treatment in advanced gastric or GEJ-ADC does not appear to improve the efficacy outcomes.

Stewart BW, Wild CP, editors. World Cancer Report 2014. Lyon, France: International Agency for Research on Cancer. 2014.

Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 2012. https://globocan.iarc.fr. Accessed September 23, 2015.

Al-Batran S-E, Lorenzen S. Management of Locally Advanced Gastro-oesophageal Cancer: Still a Multidisciplinary Global Challenge? Hematol Oncol Clin North Am. 2017;31:441–52. https://doi.org/10.1016/j.hoc.2017.01.004.CrossRefPubMed

Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24:4991–7. https://doi.org/10.1200/JCO.2006.06.8429.CrossRefPubMed

Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, et al. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastro-oesophageal adenocarcinoma. J Clin Oncol. 2005;23:5660–7. https://doi.org/10.1200/JCO.2005.17.376.CrossRefPubMed

Kim JY, Do YR, Park KU, Kim MK, Lee KH, Bae SH, et al. A multi-center phase II study of docetaxel plus cisplatin as first-line therapy in patients with metastatic squamous cell esophageal cancer. Cancer Chemother Pharmacol. 2010;66:31–6. https://doi.org/10.1007/s00280-009-1130-6.CrossRefPubMed

Quintero-Aldana G, Jorge M, Grande C, Salgado M, Gallardo E, Varela S, et al. Phase II study of first-line biweekly docetaxel and cisplatin combination chemotherapy in advanced gastric cancer. Cancer Chemother Pharmacol. 2015;76:731–7. https://doi.org/10.1007/s00280-015-2839-z.CrossRefPubMed

Woo J, Cohen SA, Grim JE. Targeted therapy in gastro-oesophageal cancers: past, present and future. Gastroenterol Rep. 2015;3:316–29. https://doi.org/10.1093/gastro/gov052.CrossRef

Cervantes A, Rodríguez Braun E, Pérez Fidalgo A, Chirivella González I. Molecular biology of gastric cancer. Clin Transl Oncol. 2007;9:208–15.CrossRef

10.

Lordick F, Kang Y-K, Chung H-C, Salman P, Oh SC, Bodoky G, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): A randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:490–9. https://doi.org/10.1016/S1470-2045(13)70102-5.CrossRefPubMed

11.

Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AFC, Frances A, et al. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14:481–9. https://doi.org/10.1016/S1470-2045(13)70096-2.CrossRefPubMedPubMedCentral

12.

Tebbutt NC, Price TJ, Ferraro DA, Wong N, Veillard A-S, Hall M, et al. Panitumumab added to docetaxel, cisplatin and fluoropyrimidine in oesophagogastric cancer: ATTAX3 phase II trial. Br J Cancer. 2016;114:505–9. https://doi.org/10.1038/bjc.2015.440.CrossRefPubMedPubMedCentral

13.

Pinto C, Di Fabio F, Barone C, Siena S, Falcone A, Cascinu S, et al. Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study). Br J Cancer. 2009;101:1261–8. https://doi.org/10.1038/sj.bjc.6605319.CrossRefPubMedPubMedCentral

14.

Chan JA, Blaszkowsky LS, Enzinger PC, Ryan DP, Abrams TA, Zhu AX, et al. A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma. Ann Oncol. 2011;22:1367–73. https://doi.org/10.1093/annonc/mdq604.CrossRefPubMedPubMedCentral

15.

Gold PJ, Goldman B, Iqbal S, Leichman LP, Zhang W, Lenz H-J, et al. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: a phase II Southwest Oncology Group Study (S0415). J Thorac Oncol. 2010;5:1472–6. https://doi.org/10.1097/JTO.0b013e3181e77a92.CrossRefPubMedPubMedCentral

16.

Park KW, Ahn JS, Park YS, Lee J, Kang JH, Park JO, et al. Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic gastric cancer. Cancer Chemother Pharmacol. 2007;59:17–211. https://doi.org/10.1007/s00280-006-0253-2.CrossRefPubMed

17.

Aoyagi K, Kouhuji K, Kizaki J, Isobe T, Hashimoto K, Shirouzu K. Molecular targeting to treat gastric cancer. World J Gastroenterol. 2014;20:13741–55. https://doi.org/10.3748/wjg.v20.i38.13741.CrossRefPubMedPubMedCentral

18.

Abraham I, Alhossan A, Lee CS, Kutbi H, MacDonald K. “Real-life” effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review. Allergy. 2015. https://doi.org/10.1111/all.12815 CrossRefPubMed

19.

Pasini F, Fraccon AP, Modena Y, Bencivenga M, Giacopuzzi S, La Russa F, et al. Targeted therapies for advanced and metastatic adenocarcinoma of the gastro-oesophageal junction: is there something new? Gastric Cancer. 2017;20:31–42. https://doi.org/10.1007/s10120-016-0626-0.CrossRefPubMed

20.

Raufi AG, Klempner SJ. Immunotherapy for advanced gastric and esophageal cancer: preclinical rationale and ongoing clinical investigations. J Gastrointest Oncol. 2015;6:561–9. https://doi.org/10.3978/j.issn.2078-6891.2015.037.CrossRefPubMedPubMedCentral

Title: First-line panitumumab plus docetaxel and cisplatin in advanced gastric and gastro-oesophageal junction adenocarcinoma: results of a phase II trial
Authors: G. Quintero Aldana
M. Salgado
S. Candamio
J. C. Méndez
M. Jorge
M. Reboredo
L. Vázquez Tuñas
C. Romero
M. Covela
A. Fernández Montes
M. Carmona
Y. Vidal Insua
R. López
the Galician Oncological Research Group (GGIO)
Publication date: 01-04-2020
Publisher: Springer International Publishing
Keywords: Neutropenia
Gastric Cancer
Gastric Cancer
Cetuximab
Panitumumab
Cytostatic Therapy
Published in: Clinical and Translational Oncology / Issue 4/2020
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-019-02151-6

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