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Phase II clinical trial with axitinib as maintenance therapy in patients (p) with metastatic colorectal carcinoma (CRC)

Date

08 Oct 2016

Session

Poster Display

Presenters

Cristina Gravalos

Citation

Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370

Authors

C. Gravalos1, A. Carrato2, M. Tobeña3, E. Grande Pulido2, G. Soler4, J. Vieitez5, L. Robles6, M. Valladares-Ayerbes7, E. Polo8, M.L. Limon9, M.J. Safont10, C. Lopez11, P. García Alfonso12, E. Aranda13

Author affiliations

  • 1 Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 2 Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 3 Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08026 - Barcelona/ES
  • 4 Medical Oncology, ICO Hospital Duran i Reynals, Hospitalet/ES
  • 5 Medical Oncologist, Hospital Universitario Central de Asturias, Oviedo/ES
  • 6 Medical Oncology, University Hospital 12 De Octubre, 28031 - Madrid/ES
  • 7 Medical Oncology, Hospital Universitario a Coruna - a Corunac, A Coruna/ES
  • 8 Medical Oncology, Hospital Miguel Servet, Zaragoza/ES
  • 9 Medical Oncology, Hospital Universitario Virgen del Rocio, Sevilla/ES
  • 10 Medical Oncology, Hospital General Universitario Valencia, Valencia/ES
  • 11 Medical Oncology, Hospital Universitario Marques de Valdecilla, Santander/ES
  • 12 Medical Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 13 Medical Oncology, Reina Sofía Hospital, University of Córdoba, Maimonides Institute of Biomedical Research (IMIBIC). Spanish Cancer Network (RTICC), Instituto de Salud Carlos III,, 14004 - Cordoba/ES
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Resources

Background

The prognosis of advanced CRC p has improved during last years. Nevertheless, treatment options in this situation are still limited. Maintenance therapy with bevacizumab has been stablished as standard of care after bevacizumab plus fluropyrimidine based chemotherapy. Axitinib is a novel drug targeting VEGFR1, 2 and 3, with contradictory results in CRC

Methods

In this phase 2 randomized double blinded trial, axitinib (5 mg/bid) was compared to placebo in metastatic CRC p who had not progressed after 6-8 months of first line treatment with chemotherapy with or without bevacizumab or cetuximab. The primary objective was progression-free survival (PFS) at 6 months. Secondary objectives included overall survival (OS), response rate (RR) and safety

Results

A total of 49 p were included: 25 cohort A (axitinib) and 24 cohort B (placebo). Baseline characteristics were well balanced. Mean age was 66 years (Standard Deviation (SD) ±10.35); 33 (67%) were men; ECOG Performance status was 0 for 19 p and 1 for 30 p. PFS at 6 months was 40% (Confidence Interval (CI) 95% 21.28, 58.12) for cohort A and 8.33% (CI95% 1.44, 23.30) for cohort B; p-value p = 0.01. Median PFS was 4.96 months in cohort A and 3.16 months for cohort B; Hazard Ratio (HR) 0.46 (0.2515, 0.8565), p = 0.0116. Median OS was 27.61 months in cohort A (CI: 14.96; 38.94), and 19.99 months (CI: 12.08; 27.35) in cohort B, p = 0.3279. The study was prematurely closed due to lack of accrual; however p-value of the log-rank contrast was significant. Regarding safety, grade 3-4 treatment related toxicities were experienced by 7 p (28%) in cohort A and 1 p (4%) in cohort B. The most frequent grade 3-4 treatment related toxicities were hypertension in 6% and 2%; diarrhea in 4% and 0%, asthenia in 2% and 0% in cohort A and B, respectively. There were no toxic deaths

Conclusions

Maintenance treatment with axitinib in advanced CRC with no progression after first line chemotherapy is associated with a significantly increased PFS when compared to placebo. Axitinib was well tolerated with few SAEs. The initially estimated sample size was not reached, but the study drug should be further studied in this setting since promising efficacy data were met

Clinical trial identification

EudraCT: 2011-002384-16

Legal entity responsible for the study

Spanish Cooperative Group for the Digestive Tumour Therapy

Funding

Pfizer, New York, NY, USA

Disclosure

A. Carrato: Consultant or advisore role: Amgen, Merck, Roche. M. Valladares-Ayerbes: Consultant or advisory role: Amgen, Bayer. C. Lopez: Consultant or advisory role Amgen, Pfizer, Celgene, Sanofi, Roche, Novartis, Ipsen. P. García Alfonso: Advisory role: Roche, Merck, Amgen, Sanofi, Lilly y Bayer. E. Aranda: advisory role from Amgen, Bayer, Celgene, Merk, Roche and Sanofi. All other authors have declared no conflicts of interest.

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