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Lung Cancer. 2017 Nov;113:51-58. doi: 10.1016/j.lungcan.2017.08.014. Epub 2017 Aug 31.

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.

Author information

1
Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN, USA. Electronic address: leora.horn@vanderbilt.edu.
2
Yale University School of Medicine and Yale Cancer Center, 333 Cedar Street, FMP 127, New Haven, CT, USA. Electronic address: scott.gettinger@yale.edu.
3
University of Colorado Cancer Center, 12801 E. 17th Avenue, Aurora, CO, USA. Electronic address: ross.camidge@ucdenver.edu.
4
Vrije Universiteit VU Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Electronic address: EF.Smit@vumc.nl.
5
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 300 E66th Street, Room 1033, New York, NY, USA. Electronic address: janjigiy@mskcc.org.
6
Foundation Medicine, Inc., 150 Second Street, Cambridge, MA, USA. Electronic address: vmiller@foundationmedicine.com.
7
Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN, USA. Electronic address: william.pao@vanderbilt.edu.
8
Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, Biberach, Germany. Electronic address: matthias.freiwald@boehringer-ingelheim.com.
9
Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: jean.fan@boehringer-ingelheim.com.
10
Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: bushi.wang@boehringer-ingelheim.com.
11
Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: vikramkchand@gmail.com.
12
University of Groningen and University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands. Electronic address: h.j.m.groen@umcg.nl.

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.

KEYWORDS:

Afatinib; Cetuximab; EGFR; NSCLC; Phase Ib

PMID:
29110849
DOI:
10.1016/j.lungcan.2017.08.014
[Indexed for MEDLINE]
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