Top

Published in:

01-09-2013 | Review

The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials

Authors: F. Petrelli, K. Borgonovo, S. Barni

Published in: Targeted Oncology | Issue 3/2013

Abstract

Skin rash is an early and frequent phenomenon during treatment with anti-epidermal growth factor receptor monoclonal antibodies. The objective of this review is to assess the predictive value of skin rash in patients with advanced colorectal cancer treated with cetuximab and panitumumab. We searched PubMed and ASCO Meetings for publications reporting the correlation of skin rash with survival and/or response rate. Hazard ratios (HRs) with 95 % confidence intervals for progression and/or survival, and/or risk ratios (RRs) for response rate in patients with rash were obtained from publications and pooled in a meta-analysis. Fourteen publications (for a total of 3,833 patients) were included in this meta-analysis. The occurrence of skin toxicity represents a predictive factor for survival (HR 0.51; p < 0.00001) and progression (HR 0.58; p < 0.00001). Similarly, patients who developed moderate or severe rash had an increased chance of response (35 vs 13 %; RR 2.23, p < 0.00001). The occurrence of skin rash during treatment with cetuximab and panitumumab represents a significant predictor of the efficacy of these drugs. The hypothesis that, in patients who lack substantial skin toxicity, this treatment is not beneficial and requires early discontinuation deserves further study.

Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon J-L, Van Laethem J-L et al (2007) Open-label phase iii trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25(13):1658–1664PubMedCrossRef

Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R et al (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26(10):1626–1634PubMedCrossRef

Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D’Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360(14):1408–1417PubMedCrossRef

Lacouture ME, Anadkat MJ, Bensadoun RJ, Bryce J, Chan A, Epstein JB, Eaby-Sandy B, Murphy BA, MASCC Skin Toxicity Study Group (2011) Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer 19(8):1079–1095, Epub 2011 Jun 1PubMedCrossRef

Pinto C, Barone CA, Girolomoni G, Russi EG, Merlano MC, Ferrari D, Maiello E, American Society of Clinical Oncology, European Society of Medical Oncology (2011) Management of skin toxicity associated with cetuximab treatment in combination with chemotherapy or radiotherapy. Oncologist 16(2):228–238, Epub 2011 Jan 27PubMedCrossRef

Burtness B, Anadkat M, Basti S, Hughes M, Lacouture ME, McClure JS, Myskowski PL, Paul J, Perlis CS, Saltz L, Spencer S (2009) NCCN Task Force Report: management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. J Natl Compr Cancer Netw 7(Suppl 1):S5–S21, quiz S22-4

Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351(4):337–345PubMedCrossRef

Perez-Soler R, Chachoua A, Hammond LA et al (2004) Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol 22:3238–3247PubMedCrossRef

Van Cutsem E, Humblet Y, Gelderblom H et al Cetuximab dose-escalation study in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST): Pharmacokinetic and efficacy data of a randomized study. 2007 ASCO Gastrointestinal Cancers Symposium. Abstract 237

10.

Higgins JPT, Green S (editors) (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available from www.cochrane-handbook.org

11.

DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRef

12.

Gamucci T, Nelli F, Cianci G, Grassi G, Moscetti L, Sperduti I, Zeuli M, Cortesi E, D’Auria G, Pollera CF (2008) A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer: predictive value of early specific toxicities. Clin Colorectal Cancer 7(4):273–279PubMedCrossRef

13.

Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357(20):2040–2048PubMedCrossRef

14.

Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P, Mirtsching B, Cohn AL, Pippas AW, Azarnia N, Tsuchihashi Z, Mauro DJ, Rowinsky EK (2006) Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol 24(30):4914–4921PubMedCrossRef

15.

Lévi F, Karaboué A, Gorden L, Innominato PF, Saffroy R, Giacchetti S, Hauteville D, Guettier C, Adam R, Bouchahda M (2011) Cetuximab and circadian chronomodulated chemotherapy as salvage treatment for metastatic colorectal cancer (mCRC): safety, efficacy and improved secondary surgical resectability. Cancer Chemother Pharmacol 67(2):339–348PubMedCrossRef

16.

Paez D, Paré L, Espinosa I, Salazar J, del Rio E, Barnadas A, Marcuello E, Baiget M (2010) Immunoglobulin G fragment C receptor polymorphisms and KRAS mutations: are they useful biomarkers of clinical outcome in advanced colorectal cancer treated with anti-EGFR-based therapy? Cancer Sci 101(9):2048–2053PubMedCrossRef

17.

Park JH, Han SW, Oh DY, Im SA, Jeong SY, Park KJ, Kim TY, Bang YJ, Park JG (2011) Analysis of KRAS, BRAF, PTEN, IGF1R, EGFR intron 1 CA status in both primary tumors and paired metastases in determining benefit from cetuximab therapy in colon cancer. Cancer Chemother Pharmacol 68(4):1045–1055PubMedCrossRef

18.

Racca P, Fanchini L, Caliendo V, Ritorto G, Evangelista W, Volpatto R, Milanesi E, Ciorba A, Paris M, Facilissimo I, Macripò G, Clerico M, Ciuffreda L (2008) Efficacy and skin toxicity management with cetuximab in metastatic colorectal cancer: outcomes from an oncologic/dermatologic cooperation. Clin Colorectal Cancer 7(1):48–54PubMedCrossRef

19.

Jehn CF, Böning L, Kröning H, Possinger K, Lüftner D (2012) Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer. Br J Cancer 106(2):274–278PubMedCrossRef

20.

Koza I Sr, Wrba F, Vrbanec D et al (2009) Correlation of KRAS status with clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) treated first-line with FOLFOX6 + cetuximab (FX + C) or FOLFIRI + cetuximab (FF + C): The CECOG/CORE1.2.001 trial. J Clin Oncol 27:15s, suppl; abstr 4055CrossRef

21.

Berlin J, Van Cutsem E, Peeters M et al (2007) Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): A pooled analysis of five clinical trials. J Clin Oncol 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement): 4134

22.

Sobrero AF, Peeters M, Price TJ et al (2012) Final results from study 181: Randomized phase III study of FOLFIRI with or without panitumumab (pmab) for the treatment of second-line metastatic colorectal cancer (mCRC). J Clin Oncol 30 (suppl 4; abstr 387)

23.

Douillard YJ, Siena S, Tabernero J et al (2012) Final skin toxicity (ST) and patient-reported outcomes (PRO) results from PRIME: A randomized phase III study of panitumumab (pmab) plus FOLFOX4 (CT) for first-line metastatic colorectal cancer (mCRC). J Clin Oncol 30 (suppl 4; abstr 531)

24.

Price TJ, Sobrero AF, Wilson G et al (2010) Randomized, open-label, phase III study of panitumumab (pmab) with FOLFIRI versus FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC): Efficacy by skin toxicity (ST). J Clin Oncol 28:15s, suppl; abstr 3529

25.

Stintzing S, Kapaun C, Laubender RP et al (2012) Cetuximab-related skin toxicity in metastatic colorectal cancer (mCRC) patients and its correlation with molecular markers: Results from the German AIO CRC 0104 trial. J Clin Oncol 30 (suppl 4; abstr 491)

26.

Stintzing S, Kapaun C, Laubender RP et al (2013) Prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer patients and its correlation with parameters of the epidermal growth factor receptor signal transduction pathway: results from a randomized trial of the GERMAN AIO CRC Study Group. Int J Cancer 132(1):236–245PubMedCrossRef

27.

Van Cutsem E, Tejpar S, Vanbeckevoort D et al (2012) Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. J Clin Oncol 30(23):2861–2868PubMedCrossRef

28.

Lacouture ME (2006) Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 6:803–812PubMedCrossRef

29.

Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Molec Cell Biol 2:127–137CrossRef

30.

Sobrero A, Fehrenbacher L, Rivera F et al (2007) Randomized phase III trial of cetuximab plus irinotecan alone for metastatic colorectal cancer (mCRC) in 1298 patients who have failed prior oxaliplatin-based therapy: the EPIC trial. In AACR Meeting Abstracts, p 3536-a

31.

Van Cutsem E, Nowacki M, Lang I et al (2007) Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. J Clin Oncol, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 4000

32.

Petrelli F, Borgonovo K, Cabiddu M et al (2011) Cetuximab and panitumumab in KRAS wild-type colorectal cancer: a meta-analysis. Int J Color Dis 26(7):823–833CrossRef

Title: The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials
Authors: F. Petrelli
K. Borgonovo
S. Barni
Publication date: 01-09-2013
Publisher: Springer Paris
Published in: Targeted Oncology / Issue 3/2013
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-013-0257-x

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2013

Lung cancer-initiating cells: a novel target for cancer therapy

Is 1,25-dihydroxyvitamin D3 receptor expression a potential Achilles’ heel of CD44+ oral squamous cell carcinoma cells?

ASCO 2013: from the rediscovery of old recipes to targeted oncology

Bevacizumab-based treatment in colorectal cancer with a NRAS Q61K mutation

The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients

Clinical activity of sunitinib in patients with advanced desmoplastic round cell tumor: a case series

Keynote webinar | Spotlight on antibody–drug conjugates in cancer