title: 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.
abstract: BACKGROUND
  This phase 2 trial (ClinicalTrials.gov 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 KRAS wild-type non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with advanced NSCLC, progression on 1 or 2 regimens of chemotherapy and erlotinib, KRAS wild-type or known EGFR-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.
  
  
  RESULTS
  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 P = .372 for null hypothesis [H0 ]: ORR ≤ 5%) and 6% (1 partial response) for patients with nonadenocarcinoma. Responders included: 2 of 25 EGFR mutation-positive tumors; 1 of 3 EGFR wild-type with HER2 amplification. Median progression-free survival was 12 weeks overall (n = 66) and 18 weeks (n = 26) for patients with EGFR 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.
  
  
  CONCLUSIONS
  Dacomitinib demonstrated preliminary activity and acceptable tolerability in heavily pretreated patients, and may offer benefit in molecularly defined patient subsets.
authors: City of Hope, Duarte, California.
authors: Karen L
authors: KL
authors: Reckamp
authors: Giuseppe
authors: G
authors: Giaccone
authors: D Ross
authors: DR
authors: Camidge
authors: Shirish M
authors: SM
authors: Gadgeel
authors: Fadlo R
authors: FR
authors: Khuri
authors: Jeff A
authors: JA
authors: Engelman
authors: Marianna
authors: M
authors: Koczywas
authors: Arun
authors: A
authors: Rajan
authors: Alicyn K
authors: AK
authors: Campbell
authors: Diana
authors: D
authors: Gernhardt
authors: Ana
authors: A
authors: Ruiz-Garcia
authors: Stephen
authors: S
authors: Letrent
authors: Jane
authors: J
authors: Liang
authors: Ian
authors: I
authors: Taylor
authors: Joseph P
authors: JP
authors: O'Connell
authors: Pasi A
authors: PA
authors: Jänne
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D052999:Quinazolinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D011799:Quinazolines; D052999:Quinazolinones; C525726:dacomitinib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors
keywords: PF-00299804; adenocarcinoma; dacomitinib; erlotinib; non-small cell lung cancer; nonadenocarcinoma