Mitchell-Richards, Kisha

1 Background: To determine whether changing chemotherapy (CT) during pre-op chemoradiation (CRT) based on response to induction CT by 18F-fluoro-deoxyglucose PET imaging can lead to improved pathologic complete response (pCR) in patients (pts) with resectable esophageal and gastroesophageal junction (GEJ) adenocarcinomas. Methods: 257 eligible pts were enrolled, underwent baseline PET scan, and were randomized to one of 2 induction CT arms: Modified FOLFOX-6 (oxaliplatin, leucovorin, 5-FU), days 1, 15, 29 or Carboplatin/Paclitaxel (CP), days 1, 8, 22, 29. Repeat PET was performed days 36-42; change in max standardized uptake value (SUV) from baseline was assessed. PET non-responders (≤35% decrease in SUV – PET-NR) crossed over to alternative CT regimen during CRT (50.4Gy/28 fractions). PET responders (>35% decrease in SUV – PET-R) continued on same CT during CRT. Pts underwent surgery 6 wks post-CRT. Pts evaluable if had surgery, disease progression (PD), death due to disease, were unresectable or had adverse event (AE). Primary endpoint was pCR in PET-NR who crossed over to alternative CT (expected 5% under H0 to 20% under Ha). Results: Pre-audit PET response data after induction CT and pCR rates after CRT and surgery are shown in the table. For PET-NR who crossed over to alternative CT during CRT, pCR was 15.6%; 95% CI (0.08, 0.26). Conclusions: Efficacy criteria were met for an improvement in pCR rates among pts who were PET-NR after induction CT and received alternative CT during CRT for esophageal and GEJ adenoca. Pts receiving induction and concurrent CP had an unexpectedly low pCR. Support: U10CA180821, U10CA180882 Clinical trial information: NCT01333033. [Table: see text]

Abstract Background: Overexpression of COX-2 has been associated with worse outcome in NSCLC. In C30203, we found that administration of the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved outcome (progression free and overall survival, PFS, OS) in pts with moderate to high COX-2 expression by immunohistochemistry (IHC). C30801 was designed to prospectively confirm that finding. Patients and Methods: Pts with NSCLC (stage IIIb with pleural effusion, IV 6th ed) were pre-registered and biopsy specimens analyzed for COX-2 by IHC. Pts with COX-2 expression > or = 2, PS 0-2 and normal organ function were eligible. Chemotherapy was determined by histology: carboplatin (AUC = 6), pemetrexed (500 mg/m2) d 1, q21 days for pts with non-squamous NSCLC; carboplatin(AUC=5.5) d1, gemcitabine (1000 mg/m2) d 1,8 for pts with squamous histology. Randomization was to celecoxib (400 mg bid) (Arm A) or placebo (Arm B). The primary endpoint was to demonstrate improvement in PFS in patients with COX-2 index >=4 with hazard ratio of 0.645. Results: The study was halted by the DSMB for futility after 312 of the planned 322 pts were randomized. The current analysis is based upon the first 300 pts. There were no significant differences between the groups (Table). There was a possible harmful effect for COX-2 inhibition in the COX-2 2-3 subset (OS HR = 1.75, p =.0977). Toxicity was similar for both arms. Subset analyses evaluating histology, chemotherapy regimen, incremental COX-2 expression did not demonstrate any advantage for COX-2 inhibition. Conclusions: 1. COX-2 expression by IHC failed to select pts who could benefit from selective COX-2 inhibition. 2. COX-2 inhibition did not significantly increase toxicity associated with chemotherapy or increase cardiovascular morbidity. 3. We will evaluate other possible determinants of toxicity and response to COX-2 inhibition. OutcomeArm AArm BCOX-2 2-3 (n=37)COX-2 > or = 4 (n=111)COX-2 2-3 (n=46)COX-2 > or = 4 (n=106)PFS (months)4.404.934.606.11OS (months)9.0310.5814.8512.68 Citation Format: Martin J. Edelman, Xiaofei Wang, Lydia Hodgson, Richard T. Cheney, Maria Baggstrom, Thomas Sachdev, Ajeet Gajra, Erin Bertino, Karen Reckamp, Julian Molina, Joan Schiller, Kisha Mitchell-Richards, Paula Friedman, Jon Ritter, Everett Vokes, Alliance for Clinical Trials in Oncology. Phase III randomized, placebo controlled trial of COX-2 inhibition in addition to standard chemotherapy for advanced non-small cell lung cancer (NSCLC):CALGB 30801 (Alliance). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT238. doi:10.1158/1538-7445.AM2014-CT238