Phase I/II trial of cetuximab and erlotinib in patients with lung adenocarcinoma and acquired resistance to erlotinib Journal Article


Authors: Janjigian, Y. Y.; Azzoli, C. G.; Krug, L. M.; Pereira, L. K.; Rizvi, N. A.; Pietanza, M. C.; Kris, M. G.; Ginsberg, M. S.; Pao, W.; Miller, V. A.; Riely, G. J.
Article Title: Phase I/II trial of cetuximab and erlotinib in patients with lung adenocarcinoma and acquired resistance to erlotinib
Abstract: Purpose: In patients with epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma, treatment with erlotinib or gefitinib is associated with a 75% radiographic response rate and progressionfree survival of approximately 12 months. The most common mechanism of acquired resistance to erlotinib is development of a secondary mutation in EGFR, suggesting that these tumors continue to depend on EGFR signaling. We hypothesized that combined EGFR blockade would overcome acquired resistance to erlotinib in patients with lung adenocarcinoma. To evaluate the toxicity and efficacy of cetuximab and erlotinib in patients with acquired resistance to erlotinib, we conducted this phase I/II clinical trial. Experimental Design: Patients with lung adenocarcinoma and clinically defined acquired resistance to erlotinib were treated with erlotinib 100 mg daily, along with cetuximab every 2 weeks in three escalating dose cohorts (250 mg/m2, 375 mg/m2, and 500 mg/m2). The recommended phase II dose was then evaluated in a two-stage trial, with a primary end point of objective response rate. Results: A total of 19 patients were enrolled. The most common toxicities for the combination of cetuximab and erlotinib were rash, fatigue, and hypomagnesemia. The recommended phase II dose identified was cetuximab 500 mg/m2 every 2 weeks and erlotinib 100 mg daily. At this dose and schedule, no radiographic responses were seen (0 of 13, 0%, 95% CI, 0-25). Conclusions: Combined EGFR inhibition, with cetuximab 500 mg/m2every 2 weeks and erlotinib 100 mg daily, had no significant activity in patients with acquired resistance to erlotinib. © 2011 AACR.
Keywords: adult; clinical article; treatment outcome; aged; overall survival; fatigue; erlotinib; drug dose reduction; drug withdrawal; hypophosphatemia; recommended drug dose; side effect; edema; progression free survival; phase 2 clinical trial; anemia; leukopenia; mucosa inflammation; nausea; thrombocytopenia; epidermal growth factor receptor; creatinine blood level; cetuximab; alanine aminotransferase blood level; aspartate aminotransferase blood level; drug dose escalation; hyperglycemia; hypomagnesemia; rash; hyperkalemia; hypokalemia; hyponatremia; lung adenocarcinoma; phase 1 clinical trial; drug treatment failure; bilirubin blood level; hypernatremia; partial thromboplastin time; paronychia; conjunctivitis; receptor down regulation
Journal Title: Clinical Cancer Research
Volume: 17
Issue: 8
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2011-04-15
Start Page: 2521
End Page: 2527
Language: English
DOI: 10.1158/1078-0432.ccr-10-2662
PROVIDER: scopus
PUBMED: 21248303
DOI/URL:
Notes: --- - "Export Date: 23 June 2011" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Michelle S Ginsberg
    158 Ginsberg
  2. Lee M Krug
    211 Krug
  3. Christopher G Azzoli
    105 Azzoli
  4. William Pao
    141 Pao
  5. Naiyer A Rizvi
    156 Rizvi
  6. Maria C Pietanza
    115 Pietanza
  7. Vincent Miller
    261 Miller
  8. Yelena Yuriy Janjigian
    145 Janjigian
  9. Gregory J Riely
    344 Riely
  10. Mark Kris
    597 Kris