A Single Institutional Experience with Panitumumab in Metastatic Colorectal Cancer

Sigurdis Haraldsdottir, Jeffrey S. Rose, Christina Wu, Lai Wei, Richard M. Goldberg, Tanios Bekaii-Saab

The Ohio State University Comprehensive Cancer Center, Columbus, USA..

DOI: 10.4236/jct.2012.326121                

Abstract

Introduction: Panitumumab is an EGFR inhibitor approved for use in metastatic refractory colorectal cancer. It is unclear whether patients who have progressed on cetuximab may benefit from subsequent panitumumab therapy. This retrospective analysis was conducted to describe the experience at The Ohio State University with panitumumab including in patients who have progressed on cetuximab. Methods: Patients who received at least 1 dose of panitumumab between September 2006 and December 2011 were identified using the hospital’s pharmacy database. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 was used to assess responses and Kaplan-Meier curves were used to estimate progression-free survival (PFS) and overall survival (OS). Results: Eighty-seven patients (median age 61 years) were identified. Sixty-seven percent of patients had tumors with wild-type KRAS, 3.4% had tumors with mutated KRAS and the KRAS status was unknown in 29.9%. Twenty-four percent of the patients had an ECOG performance status of 2 or above and 59.8% of patients had received ≥ 2 prior lines of chemotherapy. Thirty-two percent of patients received single-agent panitumumab while 68% received it in combination with chemotherapy. Of the patients with KRAS wild-type tumors, 10 (17.2%) had objective responses (3 complete, 7 partial) and 26 (44.8%) had stable disease. Median PFS and OS were 5.0 and 9.0 months. The presence of a rash, improved ECOG performance status and coadministration with either irinotecan or FOLFIRI, led to a significantly better OS in univariate analysis. Among patients who had clinical benefit with cetuximab, 71% had subsequent clinical benefit with panitumumab therapy. Conclusions: In our single institution analysis of patients who received panitumumab, the number of prior lines of therapy did not significantly affect OS, suggesting that panitumumab retains its efficacy in the 2^nd and 3^rd line setting. Additionally, panitumumab can benefit patients who previously had clinical benefit with cetuximab.

Keywords

Panitumumab; Cetuximab; EGFR Inhibitor; Metastatic Colorectal Cancer

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	R. Siegel, E. Ward, O. Brawley and A. Jemal, “Cancer Statistics, 2011: The Impact of Eliminating Socioeconomic and Racial Disparities on Premature Cancer Deaths,” CA: A Cancer Journal for Clinicians, Vol. 61, No. 4, 2011, pp. 212-236. doi:10.3322/caac.20121
[2]	H. K. Sanoff, D. J. Sargent, M. E. Campbell, R. F. Morton, C. S. Fuchs, R. K. Ramanathan, et al., “Five-Year Data and Prognostic Factor Analysis of Oxaliplatin and Irinotecan Combinations for Advanced Colorectal Cancer: N9741,” Journal of Clinical Oncology, Vol. 26, No. 35, 2008, pp. 5721-5727. doi:10.1200/JCO.2008.17.7147
[3]	A. Lievre, J. B. Bachet, D. Le Corre, V. Boige, B. Landi, J. F. Emile, et al., “KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer,” Cancer Research, Vol. 66, No. 8, 2006, pp. 3992-3995. doi:10.1158/0008-5472.CAN-06-0191
[4]	R. G. Amado, M. Wolf, M. Peeters, E. Van Cutsem, S. Siena, D. J. Freeman, et al., “Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients with Metastatic Colorectal Cancer,” Journal of Clinical Oncology, Vol. 26, No. 10, 2008, pp. 1626-1634. doi:10.1200/JCO.2007.14.7116
[5]	M. Peeters, T. J. Price, A. Cervantes, A. F. Sobrero, M. Ducreux, Y. Hotko, 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,” Journal of Clinical Oncology, Vol. 28, No. 31, 2010, pp. 4706-4713. doi:10.1200/JCO.2009.27.6055
[6]	J. Y. Douillard, S. Siena, J. Cassidy, J. Tabernero, R. Burkes, M. Barugel, 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,” Journal of clinical oncology, Vol. 28, No. 31, 2010, pp. 4697-4705. doi:10.1200/JCO.2009.27.4860
[7]	T. S. Maughan, R. A. Adams, C. G. Smith, A. M. Meade, M. T. Seymour, R. H. Wilson, et al., “Addition of Cetu- ximab to Oxaliplatin-Based First-Line Combination Chemotherapy for Treatment of Advanced Colorectal Cancer: Results of The Randomised Phase 3 MRC COIN Trial,” Lancet, Vol. 377, No. 9783, 2011, pp. 2103-2114. doi:10.1016/S0140-6736(11)60613-2
[8]	K. M. Tveit, T. Guren, B. Glimelius, P. Pfeiffer, H. Sorbye, S. Pyrhonen, et al., “Phase III Trial of Cetuximab with Continuous or Intermittent Fluorouracil, Leucovorin, and Oxaliplatin (Nordic FLOX) versus FLOX Alone in First-Line Treatment of Metastatic Colorectal Cancer: The NORDIC-VII Study,” Journal of clinical oncology, Vol. 30, No. 15, 2012, pp. 1755-1762. doi:10.1200/JCO.2011.38.0915
[9]	J. Taieb, T. S. Maughan, C. Bokemeyer, E. Van Cutsem, T. Brodowicz, G. Folprecht, et al., “Cetuximab Combined with Infusional 5-Fluorouracil/Folinic Acid (5-FU/FA) and Oxaliplatin in Metastatic Colorectal Cancer (mCRC): A Pooled Analysis of COIN and OPUS Study Data,” Journal of Clinical Oncology, Vol. 30, 2012, Abstract 3574.
[10]	J. Metges, J. Raoul, N. Achour, O. Capitain, A. Gourlaouen, J. Ramee, et al., “PANERB Study: Panitumumab after Cetuximab-Based Regimen Failure,” Journal of Clinical Oncology, Vol. 28, No. 15, 2010, p. e14000.
[11]	R. C. Wadlow, A. F. Hezel, T. A. Abrams, L. S. Blaszkowsky, C. S. Fuchs, M. H. Kulke, et al., “Panitumumab in Patients with KRAS Wild-Type Colorectal Cancer after Progression on Cetuximab,” The Oncologist, Vol. 17, No. 1, 2012, pp. e27-e34.
[12]	M. W. Saif, K. Kaley, E. Chu and M. S. Copur, “Safety and Efficacy of Panitumumab Therapy after Progression with Cetuximab: Experience at Two Institutions,” Clinical Colorectal Cancer, Vol. 9, No. 5, 2010, pp. 315-318. doi:10.3816/CCC.2010.n.046
[13]	D. Power, M. Shah, T. Asmis, J. Garcia and N. Kemeny, “Safety and Efficacy of Panitumumab Following Cetuximab: Retrospective Review of the Memorial Sloan-Kettering Experience,” Investigational New Drugs, Vol. 28, No. 3, 2010, pp. 353-360. doi:10.1007/s10637-009-9268-y
[14]	E. A. Eisenhauer, P. Therasse, J. Bogaerts, L. H. Schwartz, D. Sargent, R. Ford, et al., “New Response Evaluation Criteria in Solid Tumours: Revised RECIST Guideline (Version 1.1),” European Journal of Cancer, Vol. 45, No. 2, 2009, pp. 228-247. doi:10.1016/j.ejca.2008.10.026
[15]	D. J. Sargent, C. H. Kohne, H. K. Sanoff, B. M. Bot, M. T. Seymour, A. de Gramont, et al., “Pooled Safety and Efficacy Analysis Examining the Effect of Performance Status on Outcomes in Nine First-Line Treatment Trials Using Individual Data from Patients with Metastatic Colorectal Cancer,” Journal of Clinical Oncology, Vol. 27, No. 12, 2009, pp. 1948-1955. doi:10.1200/JCO.2008.20.2879
[16]	M. Peeters, S. Siena, E. Van Cutsem, A. Sobrero, A. Hendlisz, S. Cascinu, 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, Vol. 115, No. 7, 2009, pp. 1544-1554. doi:10.1002/cncr.24088
[17]	D. Cunningham, Y. Humblet, S. Siena, D. Khayat, H. Bleiberg, A. Santoro, et al., “Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer,” New England Journal of Medicine, Vol. 351, No. 4, 2004, pp. 337-345. doi:10.1056/NEJMoa033025
[18]	M. Yashiro, H. Qiu, T. Hasegawa, X. Zhang, T. Matsuzaki and K. Hirakawa, “An EGFR Inhibitor Enhances the Efficacy of SN38, an Active Metabolite of Irinotecan, in SN38-Refractory Gastric Carcinoma Cells,” British Journal of Cancer, Vol. 105, No. 10, 2011, pp. 1522-1532. doi:10.1038/bjc.2011.397
[19]	J. Franko, Q. Shi, C. D. Goldman, B. A. Pockaj, G. D. Nelson, R. M. Goldberg, et al., “Treatment of Colorectal Peritoneal Carcinomatosis with Systemic Chemotherapy: A Pooled Analysis of North Central Cancer Treatment Group Phase III Trials N9741 and N9841,” Journal of Clinical Oncology, Vol. 30, No. 3, 2011, pp. 263-267.
[20]	S. Tejpar, I. Celik, M. Schlichting, U. Sartorius, C. Bokemeyer and E. Van Cutsem, “Association of KRAS G13D Tumor Mutations with Outcome in Patients with Metastatic Colorectal Cancer Treated with First-Line Chemotherapy with or Without Cetuximab,” Journal of Clinical Oncology, Jun 25 2012 [Epub Ahead of Print].
[21]	C. Montagut, A. Dalmases, B. Bellosillo, M. Crespo, S. Pairet, M. Iglesias, et al., “Identification of a Mutation in the Extracellular Domain of the Epidermal Growth Factor Receptor conferring Cetuximab Resistance in Colorectal Cancer,” Nature Medicine, Vol. 18, No. 9, 2012, pp. 1445-1445. doi:10.1038/nm0912-1445b