A phase 2 trial of dacomitinib (PF‐00299804), an oral, irreversible pan‐HER (human epidermal growth factor receptor) inhibitor, in patients with advanced non–small cell lung cancer after failure of prior chemotherapy and erlotinib. Issue 8 (5th February 2014)

• Record Type: Journal Article
• Authors: Reckamp, Karen L.; Giaccone, Giuseppe; Camidge, D. Ross; Gadgeel, Shirish M.; Khuri, Fadlo R.; Engelman, Jeff A.; Koczywas, Marianna; Rajan, Arun; Campbell, Alicyn K.; Gernhardt, Diana; Ruiz‐Garcia, Ana; Letrent, Stephen; Liang, Jane; Taylor, Ian; O'Connell, Joseph P.; Jänne, Pasi A.
• Is Part Of: Cancer. Volume 120:Issue 8(2014)
• Page Start: 1145
• Page End: 1154
• Publication Date: 2014-02-05
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28561
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28561-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>This phase 2 trial (<ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> identifier NCT00548093) assessed the efficacy, safety, and impact on health‐related quality of life of dacomitinib (PF‐00299804), an irreversible tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptors (EGFR)/HER1, HER2, and HER4, in patients with <italic>KRAS</italic> wild‐type non–small cell lung cancer (NSCLC).</p> </sec> <sec id="cncr28561-sec-0002" sec-type="section"> <title>METHODS</title> <p>Patients with advanced NSCLC, progression on 1 or 2 regimens of chemotherapy and erlotinib, <italic>KRAS</italic> wild‐type or known <italic>EGFR‐</italic>sensitizing mutant tumor, and Eastern Cooperative Oncology Group performance status of 0 to 2 received 45 mg of dacomitinib once daily continuously in 21‐day cycles.</p> </sec> <sec id="cncr28561-sec-0003" sec-type="section"> <title>RESULTS</title> <p>A total of 66 patients enrolled (adenocarcinoma, n = 50; those without adenocarcinoma [nonadenocarcinoma], n = 16). The objective response rate (ORR) for patients with adenocarcinoma (primary endpoint) was 5% (2 partial responses; 1‐sided <italic>P</italic> = .372 for null hypothesis [H<sub>0</sub>]: ORR ≤ 5%) and 6% (1 partial response) for patients with nonadenocarcinoma. Responders included: 2 of 25 <italic>EGFR</italic> mutation‐positive tumors; 1 of 3 <italic>EGFR</italic> wild‐type with <italic>HER2</italic> amplification. Median progression‐free survival was 12 weeks overall (n = 66) and 18 weeks (n = 26) for patients with <italic>EGFR</italic> mutation‐positive tumors. Common treatment‐related adverse events were of grade 1 or 2 severity, manageable with standard supportive care, and included diarrhea (grade 3 [G3], 12%), acneiform dermatitis (G3, 6%), exfoliative rash (G3, 3%), dry skin (G3, 0%), fatigue (G3, 3%), and stomatitis (G3, 2%). Six patients (9%) discontinued due to treatment‐related adverse events. By patient report, NSCLC symptoms of dyspnea, cough, and pain (chest, arm/shoulder) showed improvement first observed after 3 weeks on therapy.</p> </sec> <sec id="cncr28561-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Dacomitinib demonstrated preliminary activity and acceptable tolerability in heavily pretreated patients, and may offer benefit in molecularly defined patient subsets. <bold><italic>Cancer</italic> 2014;120:1145–1154</bold>. © 2014 The Authors. <italic>Cancer</italic> published by Wiley Periodicals, Inc. on behalf of American Cancer Society.</p> </sec> </abstract>