Adding @entity3866 to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III XXXX .

@entity1 @entity137 @entity470 @entity3003 @entity1149 @entity1311 @entity1349 @entity4149 @entity420 @entity3866
PURPOSE: To test, in a single-arm, prospective, phase 2 trial, whether adding the @entity470 ( @entity470 ) @entity4149 kinase inhibitor @entity3866 to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable @entity1149 would improve survival and disease control without increasing @entity137 . METHODS AND MATERIALS: Forty-eight @entity1 with previously untreated @entity1149 received intensity modulated radiation therapy (63  Gy/35 fractions) on Monday through Friday, with chemotherapy ( @entity1311 45  mg/m  , @entity3003 area under the curve [AUC] = 2) on Mondays, for 7  weeks. All @entity1 also received the @entity470 @entity4149 kinase inhibitor @entity3866 (150  mg orally 1/d) on Tuesday-Sunday for 7  weeks, followed by consolidation @entity1311 - @entity3003 . The primary endpoint was time to progression; secondary endpoints were @entity1349 ( @entity1349 ), @entity137 , response, and disease control and whether any endpoint differed by @entity470 mutation status. RESULTS: Of 46 @entity1 evaluable for response, 40 were former or never-smokers, and 41 were evaluable for @entity470 mutations (37 wild-type [WT] and 4 mutated [all @entity420 ]). Median time to progression was 14.0  months and did not differ by @entity470 status. @entity137 was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve @entity1 (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0  months' follow-up (range, 3.6-76.5  months) for all @entity1 , median @entity1349 time was 36.5  months, and 1-, 2-, and 5-year @entity1349 rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve @entity1 had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). CONCLUSIONS: @entity137 and @entity1349 were promising, but time to progression did not meet expectations. The prevalence of distant failures underscores the need for effective systemic therapy.
