Randomized phase II trial of erlotinib beyond progression in advanced erlotinib-responsive non-small cell lung cancer

Balazs Halmos, Nathan A. Pennell, Pingfu Fu, Shumaila Saad, Shirish Gadgeel, Gregory A. Otterson, Tarek Mekhail, Michael Snell, J. Philip Kuebler, Neelesh Sharma, Afshin Dowlati

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)therapy isclearly beneficial in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance develops uniformly and the benefit of continuation of EGFRTKI therapy beyond progression remains unclear. Materials and Methods. This was a randomized phase II study of chemotherapy (arm A: pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) (arm B) in patients with progressive NSCLC following clinical benefit from erlotinib. In arm B, chemotherapy was given with erlotinib at an oral daily dose of 150 mg on days 2-19 of each cycle to minimize negative pharmacodynamic interactions. The primary endpoint was that continuation of erlotinib in this patient population could extend progression-free survival (PFS) by 50%. Results. A total of 46 patients were randomized (arm A: 24; arm B: 22). Patient characteristics were well balanced except there were more female patients in arm A (p =.075). The median PFS of patients in arm A was 5.5 months and for those in arm B, 4.4 months (p =.699). The response rates were 13% and 16% in arms A and B, respectively (p =.79). EGFR status data were available for 39 of the 46 patients and no significant difference in PFS was seen for continuing ERL beyond progression in mutation-positive patients. Substantially more toxicity was seen in arm Bthanarm A. Conclusion. There was added toxicity but no benefit with the continuation of ERL beyond progression along with chemotherapy as compared with chemotherapy alone.

Original languageEnglish (US)
Pages (from-to)1298-1303
Number of pages6
JournalOncologist
Volume20
Issue number11
DOIs
StatePublished - Aug 25 2015
Externally publishedYes

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Non-Small Cell Lung Carcinoma
Drug Therapy
Epidermal Growth Factor Receptor
Disease-Free Survival
docetaxel
Pemetrexed
Erlotinib Hydrochloride
Protein-Tyrosine Kinases
Mutation
Therapeutics
Population

Keywords

  • Epidermal growth factor receptor
  • Erlotinib
  • Non-small cell lung cancer
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Randomized phase II trial of erlotinib beyond progression in advanced erlotinib-responsive non-small cell lung cancer. / Halmos, Balazs; Pennell, Nathan A.; Fu, Pingfu; Saad, Shumaila; Gadgeel, Shirish; Otterson, Gregory A.; Mekhail, Tarek; Snell, Michael; Kuebler, J. Philip; Sharma, Neelesh; Dowlati, Afshin.

In: Oncologist, Vol. 20, No. 11, 25.08.2015, p. 1298-1303.

Research output: Contribution to journalArticle

Halmos, B, Pennell, NA, Fu, P, Saad, S, Gadgeel, S, Otterson, GA, Mekhail, T, Snell, M, Kuebler, JP, Sharma, N & Dowlati, A 2015, 'Randomized phase II trial of erlotinib beyond progression in advanced erlotinib-responsive non-small cell lung cancer', Oncologist, vol. 20, no. 11, pp. 1298-1303. https://doi.org/10.1634/theoncologist.2015-0136
Halmos, Balazs ; Pennell, Nathan A. ; Fu, Pingfu ; Saad, Shumaila ; Gadgeel, Shirish ; Otterson, Gregory A. ; Mekhail, Tarek ; Snell, Michael ; Kuebler, J. Philip ; Sharma, Neelesh ; Dowlati, Afshin. / Randomized phase II trial of erlotinib beyond progression in advanced erlotinib-responsive non-small cell lung cancer. In: Oncologist. 2015 ; Vol. 20, No. 11. pp. 1298-1303.
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abstract = "Background. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)therapy isclearly beneficial in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance develops uniformly and the benefit of continuation of EGFRTKI therapy beyond progression remains unclear. Materials and Methods. This was a randomized phase II study of chemotherapy (arm A: pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) (arm B) in patients with progressive NSCLC following clinical benefit from erlotinib. In arm B, chemotherapy was given with erlotinib at an oral daily dose of 150 mg on days 2-19 of each cycle to minimize negative pharmacodynamic interactions. The primary endpoint was that continuation of erlotinib in this patient population could extend progression-free survival (PFS) by 50{\%}. Results. A total of 46 patients were randomized (arm A: 24; arm B: 22). Patient characteristics were well balanced except there were more female patients in arm A (p =.075). The median PFS of patients in arm A was 5.5 months and for those in arm B, 4.4 months (p =.699). The response rates were 13{\%} and 16{\%} in arms A and B, respectively (p =.79). EGFR status data were available for 39 of the 46 patients and no significant difference in PFS was seen for continuing ERL beyond progression in mutation-positive patients. Substantially more toxicity was seen in arm Bthanarm A. Conclusion. There was added toxicity but no benefit with the continuation of ERL beyond progression along with chemotherapy as compared with chemotherapy alone.",
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AU - Saad, Shumaila

AU - Gadgeel, Shirish

AU - Otterson, Gregory A.

AU - Mekhail, Tarek

AU - Snell, Michael

AU - Kuebler, J. Philip

AU - Sharma, Neelesh

AU - Dowlati, Afshin

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AB - Background. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)therapy isclearly beneficial in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, acquired resistance develops uniformly and the benefit of continuation of EGFRTKI therapy beyond progression remains unclear. Materials and Methods. This was a randomized phase II study of chemotherapy (arm A: pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) (arm B) in patients with progressive NSCLC following clinical benefit from erlotinib. In arm B, chemotherapy was given with erlotinib at an oral daily dose of 150 mg on days 2-19 of each cycle to minimize negative pharmacodynamic interactions. The primary endpoint was that continuation of erlotinib in this patient population could extend progression-free survival (PFS) by 50%. Results. A total of 46 patients were randomized (arm A: 24; arm B: 22). Patient characteristics were well balanced except there were more female patients in arm A (p =.075). The median PFS of patients in arm A was 5.5 months and for those in arm B, 4.4 months (p =.699). The response rates were 13% and 16% in arms A and B, respectively (p =.79). EGFR status data were available for 39 of the 46 patients and no significant difference in PFS was seen for continuing ERL beyond progression in mutation-positive patients. Substantially more toxicity was seen in arm Bthanarm A. Conclusion. There was added toxicity but no benefit with the continuation of ERL beyond progression along with chemotherapy as compared with chemotherapy alone.

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