Skip to main content
Top
Published in: Advances in Therapy 3/2019

Open Access 01-03-2019 | Panitumumab | Original Research

Prospective Observational Cohort Study to Describe the Use of Panitumumab in Combination with Chemotherapy in Real-World Clinical Practice for Patients with Wild-Type RAS mCRC

Authors: Holger Hebart, Michael Kiehl, Jiri Tomasek, Tibor Csoszi, Reija Koukakis, George Kafatos, Anja Kuhn, Katja Bjorklof, Gaston Demonty, Tomas Buchler

Published in: Advances in Therapy | Issue 3/2019

Login to get access

Abstract

Introduction

This study aimed to better understand panitumumab use in real-life clinical practice in first- and second-line treatment of metastatic colorectal cancer in five European countries.

Methods

This is a combined analysis of two observational, non-interventional prospective cohort studies, one of which was conducted in Germany and France, the other in Bulgaria, Czech Republic, and Hungary. The studies observed patients with wild-type [Kirsten] rat sarcoma viral oncogene homolog ([K]RAS/RAS) metastatic colorectal cancer (mCRC), who had been treated with panitumumab in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in the first line or with panitumumab combined with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the second line following fluoropyrimidine-based chemotherapy. The planned duration of observation was 12 months from the first dose of panitumumab.

Results

A total of 332 patients treated with panitumumab + FOLFOX in the first line and 94 patients treated with panitumumab + FOLFIRI in the second line were analyzed. The median number of panitumumab infusions was 10.0 in first-line FOLFOX patients and 11.5 in second-line FOLFIRI patients; the median duration of panitumumab exposure was 5.7 and 6.9 months, respectively. The unadjusted overall response rate (complete or partial response) in patients with available post-baseline response assessment (n = 290) was 51.7% in first-line FOLFOX and 44.9% in second-line FOLFIRI patients. In the first-line setting, resectability was achieved in 9.3%. Reported hospitalizations were mostly cancer-related visits such as scheduled anticancer treatment administrations, tumor assessment visits, or interventions. The majority of adverse drug reactions were skin disorders, with 75.3% in first-line FOLFOX patients and 72.3% in second-line FOLFIRI patients.

Conclusion

Overall, the study results show that treatment patterns, clinical efficacy, and the safety profile of panitumumab in routine clinical practice were comparable to those in randomized controlled trials. The relatively low skin toxicity rate could be attributed to increasing experience in managing panitumumab-associated rash and some degree of underreporting.

Funding

Amgen.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11. 2013. http://globocan.iarc.fr. Accessed 15 Jan 2018. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer incidence and mortality worldwide: IARC CancerBase No. 11. 2013. http://​globocan.​iarc.​fr. Accessed 15 Jan 2018.
2.
go back to reference Kindler HL, Shulman KL. Metastatic colorectal cancer. Curr Treat Options Oncol. 2001;2(6):459–71.CrossRefPubMed Kindler HL, Shulman KL. Metastatic colorectal cancer. Curr Treat Options Oncol. 2001;2(6):459–71.CrossRefPubMed
3.
go back to reference Pazdur R, Coia L, Wagman LD, Ayoub JP. Colorectal and anal cancers. Cancer management: a multidisciplinary approach. Melville: PRR; 1999. p. 149–75. Pazdur R, Coia L, Wagman LD, Ayoub JP. Colorectal and anal cancers. Cancer management: a multidisciplinary approach. Melville: PRR; 1999. p. 149–75.
4.
go back to reference Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–422.CrossRefPubMed Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386–422.CrossRefPubMed
5.
go back to reference Cohenuram M, Saif MW. Panitumumab the first fully human monoclonal antibody: from the bench to the clinic. Anticancer Drugs. 2007;18(1):7–15.CrossRefPubMed Cohenuram M, Saif MW. Panitumumab the first fully human monoclonal antibody: from the bench to the clinic. Anticancer Drugs. 2007;18(1):7–15.CrossRefPubMed
6.
go back to reference Argiles G, Dienstmann R, Elez E, Tabernero J. Panitumumab: a summary of clinical development in colorectal cancer and future directions. Future Oncol. 2012;8(4):373–89.CrossRefPubMed Argiles G, Dienstmann R, Elez E, Tabernero J. Panitumumab: a summary of clinical development in colorectal cancer and future directions. Future Oncol. 2012;8(4):373–89.CrossRefPubMed
9.
go back to reference Peeters M, Siena S, Van Cutsem E, et al. Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy. Cancer. 2009;115(7):1544–54.CrossRefPubMed Peeters M, Siena S, Van Cutsem E, et al. Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy. Cancer. 2009;115(7):1544–54.CrossRefPubMed
10.
go back to reference Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(10):1626–34.CrossRefPubMed Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26(10):1626–34.CrossRefPubMed
11.
go back to reference Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28(31):4697–705.CrossRefPubMed Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28(31):4697–705.CrossRefPubMed
12.
go back to reference Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28(31):4706–13.CrossRefPubMed Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010;28(31):4706–13.CrossRefPubMed
13.
go back to reference Cohn AL, Shumaker GC, Khandelwal P, et al. An open-label, single-arm, phase 2 trial of panitumumab plus FOLFIRI as second-line therapy in patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2011;10(3):171–7.CrossRefPubMed Cohn AL, Shumaker GC, Khandelwal P, et al. An open-label, single-arm, phase 2 trial of panitumumab plus FOLFIRI as second-line therapy in patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2011;10(3):171–7.CrossRefPubMed
14.
go back to reference Mitchell EP, Piperdi B, Lacouture ME, et al. The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (skin toxicity evaluation protocol with panitumumab) by KRAS status. Clin Colorectal Cancer. 2011;10(4):333–9.CrossRefPubMed Mitchell EP, Piperdi B, Lacouture ME, et al. The efficacy and safety of panitumumab administered concomitantly with FOLFIRI or irinotecan in second-line therapy for metastatic colorectal cancer: the secondary analysis from STEPP (skin toxicity evaluation protocol with panitumumab) by KRAS status. Clin Colorectal Cancer. 2011;10(4):333–9.CrossRefPubMed
15.
go back to reference Kohne CH, Hofheinz R, Mineur L, et al. First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer. J Cancer Res Clin Oncol. 2012;138(1):65–72.CrossRefPubMed Kohne CH, Hofheinz R, Mineur L, et al. First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer. J Cancer Res Clin Oncol. 2012;138(1):65–72.CrossRefPubMed
16.
go back to reference Douillard JY, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369(11):1023–34.CrossRefPubMed Douillard JY, Oliner KS, Siena S, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369(11):1023–34.CrossRefPubMed
17.
go back to reference Hocking CM, Price TJ. Panitumumab in the management of patients with KRAS wild-type metastatic colorectal cancer. Ther Adv Gastroenterol. 2014;7(1):20–37.CrossRef Hocking CM, Price TJ. Panitumumab in the management of patients with KRAS wild-type metastatic colorectal cancer. Ther Adv Gastroenterol. 2014;7(1):20–37.CrossRef
19.
go back to reference Tejpar S, Stintzing S, Ciardiello F, et al. Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol. 2017;3(2):194–201. Tejpar S, Stintzing S, Ciardiello F, et al. Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol. 2017;3(2):194–201.
20.
go back to reference Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32(21):2240–7.CrossRefPubMed Schwartzberg LS, Rivera F, Karthaus M, et al. PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol. 2014;32(21):2240–7.CrossRefPubMed
21.
go back to reference Rivera F, Karthaus M, Hecht JR, et al. Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis. 2017;32(8):1179–90.CrossRefPubMedPubMedCentral Rivera F, Karthaus M, Hecht JR, et al. Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis. 2017;32(8):1179–90.CrossRefPubMedPubMedCentral
22.
go back to reference Douillard JY, Siena S, Cassidy J, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25(7):1346–55.CrossRefPubMed Douillard JY, Siena S, Cassidy J, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25(7):1346–55.CrossRefPubMed
23.
go back to reference Peeters M, Oliner KS, Price TJ, et al. Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res. 2015;21(24):5469–79.CrossRefPubMed Peeters M, Oliner KS, Price TJ, et al. Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer. Clin Cancer Res. 2015;21(24):5469–79.CrossRefPubMed
24.
go back to reference Lakomy R, Rogowski W, Piko B, Mihaylova Z, Pritzova E, Kvocekova L. Prospective noninterventional study on the use of panitumumab monotherapy in patients with recurrent or progressive colorectal cancer: the VECTIS study. Cancer Manage Res. 2015;7:311–8.CrossRef Lakomy R, Rogowski W, Piko B, Mihaylova Z, Pritzova E, Kvocekova L. Prospective noninterventional study on the use of panitumumab monotherapy in patients with recurrent or progressive colorectal cancer: the VECTIS study. Cancer Manage Res. 2015;7:311–8.CrossRef
25.
go back to reference Lerchenmueller CA, Groschek M, Kroening H, et al. Panitumumab in patients with chemorefractory metastatic colorectal cancer: final analysis from a community-based, observational study (VECTOR) in Germany. J Clin Oncol. 2013;31(suppl 4):abstr 550.CrossRef Lerchenmueller CA, Groschek M, Kroening H, et al. Panitumumab in patients with chemorefractory metastatic colorectal cancer: final analysis from a community-based, observational study (VECTOR) in Germany. J Clin Oncol. 2013;31(suppl 4):abstr 550.CrossRef
26.
go back to reference Douillard JY, Siena S, Peeters M, Koukakis R, Terwey JH, Tabernero J. Impact of early tumour shrinkage and resection on outcomes in patients with wild-type RAS metastatic colorectal cancer. Eur J Cancer. 2015;51(10):1231–42.CrossRefPubMed Douillard JY, Siena S, Peeters M, Koukakis R, Terwey JH, Tabernero J. Impact of early tumour shrinkage and resection on outcomes in patients with wild-type RAS metastatic colorectal cancer. Eur J Cancer. 2015;51(10):1231–42.CrossRefPubMed
27.
go back to reference Kripp M, Prasnikar N, Vehling-Kaiser U, et al. AIO LQ-0110: a randomized phase II trial comparing oral doxycycline versus local administration of erythromycin as preemptive treatment strategies of panitumumab-mediated skin toxicity in patients with metastatic colorectal cancer. Oncotarget. 2017;8(62):105061–71.CrossRefPubMedPubMedCentral Kripp M, Prasnikar N, Vehling-Kaiser U, et al. AIO LQ-0110: a randomized phase II trial comparing oral doxycycline versus local administration of erythromycin as preemptive treatment strategies of panitumumab-mediated skin toxicity in patients with metastatic colorectal cancer. Oncotarget. 2017;8(62):105061–71.CrossRefPubMedPubMedCentral
Metadata
Title
Prospective Observational Cohort Study to Describe the Use of Panitumumab in Combination with Chemotherapy in Real-World Clinical Practice for Patients with Wild-Type RAS mCRC
Authors
Holger Hebart
Michael Kiehl
Jiri Tomasek
Tibor Csoszi
Reija Koukakis
George Kafatos
Anja Kuhn
Katja Bjorklof
Gaston Demonty
Tomas Buchler
Publication date
01-03-2019
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 3/2019
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-019-0874-6

Other articles of this Issue 3/2019

Advances in Therapy 3/2019 Go to the issue