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Molecular Cancer Therapeutics
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Spotlight on Clinical Response

Response to Erlotinib in Patients with EGFR Mutant Advanced Non–Small Cell Lung Cancers with a Squamous or Squamous-like Component

Paul K. Paik, Anna M. Varghese, Camelia S. Sima, Andre L. Moreira, Marc Ladanyi, Mark G. Kris and Natasha Rekhtman
Paul K. Paik
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 2Department of Epidemiology and Biostatistics, and 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; 4Department of Medicine, Weill Cornell Medical College, New York, New York
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 2Department of Epidemiology and Biostatistics, and 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; 4Department of Medicine, Weill Cornell Medical College, New York, New York
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Anna M. Varghese
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 2Department of Epidemiology and Biostatistics, and 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; 4Department of Medicine, Weill Cornell Medical College, New York, New York
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 2Department of Epidemiology and Biostatistics, and 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; 4Department of Medicine, Weill Cornell Medical College, New York, New York
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Camelia S. Sima
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 2Department of Epidemiology and Biostatistics, and 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; 4Department of Medicine, Weill Cornell Medical College, New York, New York
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Andre L. Moreira
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 2Department of Epidemiology and Biostatistics, and 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; 4Department of Medicine, Weill Cornell Medical College, New York, New York
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Marc Ladanyi
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 2Department of Epidemiology and Biostatistics, and 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; 4Department of Medicine, Weill Cornell Medical College, New York, New York
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Mark G. Kris
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 2Department of Epidemiology and Biostatistics, and 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; 4Department of Medicine, Weill Cornell Medical College, New York, New York
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 2Department of Epidemiology and Biostatistics, and 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; 4Department of Medicine, Weill Cornell Medical College, New York, New York
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Natasha Rekhtman
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, and 2Department of Epidemiology and Biostatistics, and 3Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York; 4Department of Medicine, Weill Cornell Medical College, New York, New York
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DOI: 10.1158/1535-7163.MCT-12-0163 Published November 2012
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    Figure 1.

    Radiographic response to erlotinib in patients with adenosquamous and solid pseudosquamous adenocarcinomas harboring EGFR mutations. †, denotes solid (pseudosquamous) adenocarcinomas; other cases are carcinomas with a squamous component (confirmed or presumed adenosquamous carcinomas).

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    Figure 2.

    Kaplan–Meier survival curve for progression-free survival (PFS) in patients with EGFR-mutant adenosquamous and solid pseudosquamous adenocarcinomas treated with erlotinib. NR, not reached; TTP, time to progression.

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    Figure 3.

    Kaplan–Meier survival curve for overall survival (OS) in patients with EGFR-mutant adenosquamous and solid pseudosquamous adenocarcinomas treated with erlotinib. NR, not reached.

Tables

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  • Table 1.

    Clinicopathologic findings for patients with EGFR-mutant adenosquamous carcinomas

    PatientaAgeGenderRaceSmoking statusStagebBiopsy #1cBiopsy #1 mutationBiopsy #2cBiopsy #2 mutationLines of therapyEGFR TKI lineBest response to EGFR TKITTP on TKI (months)OS (months)
    1 (1)61MWhiteNeverIVSquamous (L1)dexon 19 delAdenosquamous (LLL lung)exon 19 del32nd linePR12.127.5
    2 (2)71FWhiteNeverIVSquamous (RLL lung)dexon 19 delAdenocarcinoma (RLL lung)exon 19 del21st lineUnavailable19.632.9+
    3 (3)58FWhiteNeverIVSquamous (RUL lung)exon 19 delAdenosquamous (LLL lung)†exon 19 del32nd lineSD23.632.2+
    4 (4)45FHispanicNeverIVSquamous (sacrum)exon 19 delAdenocarcinoma (pleural fluid)exon 19 del22nd lineUnavailableUnavailable15.3
    5 (5)46MAsianNeverIVSquamous (R lung)exon 19 delAdenocarcinoma (SC LN)exon 19 del11st linePR5.0+6.6+
    6 (6)73MWhiteFormer (25 PY)IVSquamous (adrenal)exon 19 delAdenocarcinoma (SC LN)insufficient23rd lineUnavailableUnavailable29.8
    7 (10)58MAsianNeverIVSquamous (bronchus)L858RSquamous (T8)insufficient11st linePR1.92.5
    8 (new)76MWhiteNeverIVeSquamous (R lung)dinsufficientAdenocarcinoma (L lung)exon 19 del11st linePR5.35.3+
    9 (new)68MWhiteNeverIVSquamous (L lung)L858RNoneN/A44th linePR2.8+24.0+
    10 (new)30FAsianNeverIVAdenosquamous (R lung)L858RNoneN/A21st linePR8.410.9+
    11 (new)50MWhiteNeverIVAdenosquamous (L lung)exon 19 delNoneN/A11st linePR9.2+9.6+

    Abbreviations: SC LN, supraclavicular lymph node; PR, partial response; SD, stable disease; PY, pack years; TTP, time to progression.

    • NOTE: The majority of patients were diagnosed with squamous cell carcinoma in at least 1 sample.

    • ↵aIn parentheses are corresponding patient IDs in reference 8.

    • ↵bStage at the time of TKI treatment.

    • ↵cBiopsy numbers are not chronological: biopsy #1 represents the index case (EGFR mutant SCC).

    • ↵dAcquired resistance biopsy.

    • ↵ePrevious stage IIA treated with induction cisplatin + pemetrexed followed by LLL lobectomy, with subsequent development of bilateral pulmonary nodules and a recurrent parenchymal lesion at the lobectomy site.

  • Table 2.

    Clinicopathologic findings for patients with EGFR-mutant solid pseudosquamous adenocarcinomas

    PatientaAgeGenderRaceSmoking statusStagebInitial diagnosis (site)MutationRe-reviewLines of therapyEGFR TKI lineBest response to EGFR TKITTP on TKI (months)OS (months)
    12 (11)89FAsianNeverIVSquamous (lung)L858RAdenocarcinoma11st lineSD7.616.5
    13 (12)53FWhiteFormer (31)IVcSquamous (lung)exon 19 delAdenocarcinoma11st linePR12.420.6+

    NOTE: Both patients were initially diagnosed with squamous cell carcinomas.

    Abbreviation: TTP, time to progression.

    • ↵aIn parentheses are corresponding patient IDs in reference 8.

    • ↵bStage at the time of TKI treatment.

    • ↵cPrevious stage IB s/p adjuvant cisplatin + docetaxel followed by RLL lobectomy, which was subsequently followed by a metastatic recurrence.

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Molecular Cancer Therapeutics: 11 (11)
November 2012
Volume 11, Issue 11
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Response to Erlotinib in Patients with EGFR Mutant Advanced Non–Small Cell Lung Cancers with a Squamous or Squamous-like Component
Paul K. Paik, Anna M. Varghese, Camelia S. Sima, Andre L. Moreira, Marc Ladanyi, Mark G. Kris and Natasha Rekhtman
Mol Cancer Ther November 1 2012 (11) (11) 2535-2540; DOI: 10.1158/1535-7163.MCT-12-0163

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Response to Erlotinib in Patients with EGFR Mutant Advanced Non–Small Cell Lung Cancers with a Squamous or Squamous-like Component
Paul K. Paik, Anna M. Varghese, Camelia S. Sima, Andre L. Moreira, Marc Ladanyi, Mark G. Kris and Natasha Rekhtman
Mol Cancer Ther November 1 2012 (11) (11) 2535-2540; DOI: 10.1158/1535-7163.MCT-12-0163
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