Phase II multicenter study of erlotinib with radiation therapy (RT) for elderly patients (pts) with esophageal carcinoma (EC): Final report.

135Background: Elderly pts with comorbidities have limited Rx options for localized EC. High EGFR expression correlates with poor response to RT. We examined the safety and efficacy of erlotinib, an oral EGFR tyrosine kinase inhibitor with RT in these pts.Methods: Pts older than 65 yrs ineligible for platinum based Rx with carcinoma of the thoracic esophagus or gastroesophageal junction received erlotinib 150mg PO QD for one year starting D1 of RT [50.4 Gy D1-28 (M-F) at 1.8 Gy per fraction]. Assessments- mucosal response by EGD 4-8 wks post RT; RECIST response by CT q3mo. Endpoints: Primary- overall survival (OS), secondary- quality of life (QOL) using the FACT-E QOL tool, progression free survival (PFS) and toxicity; correlative- pre-treatment tumor EGFR and pEGFR expression by immunohistochemistry (IHC).Results: The study was closed after 17 of planned 35 pts were included due to poor accrual. Baseline characteristics: median age 78 yrs (66-91); gender M/F: 11/6; ECOG PS 0/1/2=2/12/3; stage I-1, II=5, III=7 and IVa= 4; histology: adenocarcinoma 16, squamous cell 1; dysphagia at baseline 13/17 (76%). Median OS was 7.3 months (95% CI: 4.5-22.3) with 12 pts dead (5 alive, 3 still on treatment). Reason for coming off study (n=14): disease progression (n=6), toxicity (n=5), withdrew consent, completed one year of treatment, death from unrelated cause (n=1 each). There were 2 mucosal CRs and one residual carcinoma in situ, 3 partial endoscopic responses of the 9 pts who had post RT endoscopy. Estimated PFS is 5.3 months (95% CI: 2.4-11). Sites of progression- distant 3, locoregional 6, unknown 5 and too early 3. Estimated one year survival is 26 %, 3 pts lived >12 months. Smoking status- current/past/never 3/12/2. Treatment related toxicities (any grade n=or>5) were, rash (16), fatigue (16), diarrhea (11), lymphopenia (10), anorexia (7) and dehydration (6) and 21 grade 3/4 toxicities occurred. IHC results- EGFR, neg: 1/16; pos: 15/16 and pEGFR, neg: 2/16; pos:14/16.Conclusions: For elderly pts with localized EC and no chemotherapy options, erlotinib monotherapy with RT is a tolerable therapy with modest activity. Further studies are needed to define the role of EGFR inhibition with RT in EC.No significant financial relationships to disclose.