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Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib.
Lung Cancer 2017; 113:51-58LC

Abstract

OBJECTIVES

In a phase Ib trial, afatinib plus cetuximab demonstrated promising clinical activity (objective response rate [ORR]: 29%; median progression-free survival [PFS]: 4.7 months) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with acquired resistance to erlotinib or gefitinib. Here, a separate cohort exploring afatinib plus cetuximab after progression on afatinib is reported.

MATERIALS AND METHODS

Patients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib received afatinib 40mg daily until progression, followed by afatinib daily plus cetuximab 500mg/m2 every 2 weeks until progression or intolerable adverse events (AEs). Endpoints included safety, ORR, and PFS.

RESULTS

Thirty-seven patients received afatinib monotherapy. Two (5%) patients responded; median PFS was 2.7 months. Thirty-six patients transitioned to afatinib plus cetuximab. Four (11%) patients responded; median PFS was 2.9 months. Median PFS with afatinib plus cetuximab for patients who received afatinib monotherapy for ≥12 versus <12 weeks was 4.9 versus 1.8 months (p=0.0354), and for patients with T790M-positive versus T790M-negative tumors was 4.8 versus 1.8 months (p=0.1306). Fifty percent of patients receiving afatinib plus cetuximab experienced drug-related grade 3/4 AEs. The most frequent drug-related AEs (any grade) were diarrhea (70%), rash (49%), and fatigue (35%) with afatinib monotherapy and rash (69%), paronychia (39%), and dry skin (36%) with afatinib plus cetuximab.

CONCLUSION

Sequential EGFR blockade with afatinib followed by afatinib plus cetuximab had a predictable safety profile and demonstrated modest activity in patients with EGFR mutation-positive NSCLC with resistance to erlotinib or gefitinib. CLINICALTRIALS.

GOV IDENTIFIER

NCT01090011.

Authors+Show Affiliations

Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN, USA. Electronic address: leora.horn@vanderbilt.edu.Yale University School of Medicine and Yale Cancer Center, 333 Cedar Street, FMP 127, New Haven, CT, USA. Electronic address: scott.gettinger@yale.edu.University of Colorado Cancer Center, 12801 E. 17th Avenue, Aurora, CO, USA. Electronic address: ross.camidge@ucdenver.edu.Vrije Universiteit VU Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Electronic address: EF.Smit@vumc.nl.Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 300 E66th Street, Room 1033, New York, NY, USA. Electronic address: janjigiy@mskcc.org.Foundation Medicine, Inc., 150 Second Street, Cambridge, MA, USA. Electronic address: vmiller@foundationmedicine.com.Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN, USA. Electronic address: william.pao@vanderbilt.edu.Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, Biberach, Germany. Electronic address: matthias.freiwald@boehringer-ingelheim.com.Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: jean.fan@boehringer-ingelheim.com.Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: bushi.wang@boehringer-ingelheim.com.Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: vikramkchand@gmail.com.University of Groningen and University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands. Electronic address: h.j.m.groen@umcg.nl.

Pub Type(s)

Clinical Trial, Phase I
Journal Article

Language

eng

PubMed ID

29110849

Citation

Horn, Leora, et al. "Continued Use of Afatinib With the Addition of Cetuximab After Progression On Afatinib in Patients With EGFR Mutation-positive Non-small-cell Lung Cancer and Acquired Resistance to Gefitinib or Erlotinib." Lung Cancer (Amsterdam, Netherlands), vol. 113, 2017, pp. 51-58.
Horn L, Gettinger S, Camidge DR, et al. Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib. Lung Cancer. 2017;113:51-58.
Horn, L., Gettinger, S., Camidge, D. R., Smit, E. F., Janjigian, Y. Y., Miller, V. A., ... Groen, H. J. M. (2017). Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib. Lung Cancer (Amsterdam, Netherlands), 113, pp. 51-58. doi:10.1016/j.lungcan.2017.08.014.
Horn L, et al. Continued Use of Afatinib With the Addition of Cetuximab After Progression On Afatinib in Patients With EGFR Mutation-positive Non-small-cell Lung Cancer and Acquired Resistance to Gefitinib or Erlotinib. Lung Cancer. 2017;113:51-58. PubMed PMID: 29110849.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib. AU - Horn,Leora, AU - Gettinger,Scott, AU - Camidge,D Ross, AU - Smit,Egbert F, AU - Janjigian,Yelena Y, AU - Miller,Vincent A, AU - Pao,William, AU - Freiwald,Matthias, AU - Fan,Jean, AU - Wang,Bushi, AU - Chand,Vikram K, AU - Groen,Harry J M, Y1 - 2017/08/31/ PY - 2017/03/01/received PY - 2017/06/30/revised PY - 2017/08/15/accepted PY - 2017/11/8/entrez PY - 2017/11/8/pubmed PY - 2018/6/26/medline KW - Afatinib KW - Cetuximab KW - EGFR KW - NSCLC KW - Phase Ib SP - 51 EP - 58 JF - Lung cancer (Amsterdam, Netherlands) JO - Lung Cancer VL - 113 N2 - OBJECTIVES: In a phase Ib trial, afatinib plus cetuximab demonstrated promising clinical activity (objective response rate [ORR]: 29%; median progression-free survival [PFS]: 4.7 months) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with acquired resistance to erlotinib or gefitinib. Here, a separate cohort exploring afatinib plus cetuximab after progression on afatinib is reported. MATERIALS AND METHODS: Patients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib received afatinib 40mg daily until progression, followed by afatinib daily plus cetuximab 500mg/m2 every 2 weeks until progression or intolerable adverse events (AEs). Endpoints included safety, ORR, and PFS. RESULTS: Thirty-seven patients received afatinib monotherapy. Two (5%) patients responded; median PFS was 2.7 months. Thirty-six patients transitioned to afatinib plus cetuximab. Four (11%) patients responded; median PFS was 2.9 months. Median PFS with afatinib plus cetuximab for patients who received afatinib monotherapy for ≥12 versus <12 weeks was 4.9 versus 1.8 months (p=0.0354), and for patients with T790M-positive versus T790M-negative tumors was 4.8 versus 1.8 months (p=0.1306). Fifty percent of patients receiving afatinib plus cetuximab experienced drug-related grade 3/4 AEs. The most frequent drug-related AEs (any grade) were diarrhea (70%), rash (49%), and fatigue (35%) with afatinib monotherapy and rash (69%), paronychia (39%), and dry skin (36%) with afatinib plus cetuximab. CONCLUSION: Sequential EGFR blockade with afatinib followed by afatinib plus cetuximab had a predictable safety profile and demonstrated modest activity in patients with EGFR mutation-positive NSCLC with resistance to erlotinib or gefitinib. CLINICALTRIALS. GOV IDENTIFIER: NCT01090011. SN - 1872-8332 UR - https://www.unboundmedicine.com/medline/citation/29110849/Continued_use_of_afatinib_with_the_addition_of_cetuximab_after_progression_on_afatinib_in_patients_with_EGFR_mutation_positive_non_small_cell_lung_cancer_and_acquired_resistance_to_gefitinib_or_erlotinib_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169-5002(17)30487-7 DB - PRIME DP - Unbound Medicine ER -