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Donald Richards, MD, PhD 1,2 ; Darren M. Kocs,MD 1,3 ;

Results of Docetaxel Plus Oxaliplatin (DOCOX) +/- Cetuximab in Patients with Metastatic Gastric and/or Gastroesophageal Junction Adenocarcinoma: Results of a Randomized Phase II Study. Donald Richards, MD, PhD 1,2 ; Darren M. Kocs,MD 1,3 ;

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Donald Richards, MD, PhD 1,2 ; Darren M. Kocs,MD 1,3 ;

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  1. Results of Docetaxel Plus Oxaliplatin (DOCOX) +/- Cetuximab in Patients with Metastatic Gastric and/or Gastroesophageal Junction Adenocarcinoma: Results of a Randomized Phase II Study Donald Richards, MD, PhD1,2; Darren M. Kocs,MD1,3; Alexander I. Spira, MD1,4; A. David McCollum, MD1,5; Kristi Boehm, MS1; Feng Zhan, PhD1; Lina Asmar, PhD1 1US Oncology Research, LLC, The Woodlands, TX; 2Tyler Cancer Center, Tyler, TX; 3Texas Oncology, PA, Round Rock, TX; 4Virginia Cancer Specialists, PC , Fairfax, VA; 5Baylor-Charles Sammons Cancer Center, Dallas, TX ASCO, 2011

  2. Abstract Background Advanced adenocarcinoma of the gastroesophageal junction and adenocarcinoma of the stomach are standardly treated by combination chemotherapy resulting in minimal improvements in survival. This noncomparative study evaluated the value of adding cetuximab (C) to combination chemotherapy.

  3. Abstract Continued Methods • Primary objective - Progression-free survival (PFS). • Secondary objectives: 1-yr survival, response rate, time to response (TTR), duration of response (DOR), correlation of KRAS type of mutation to response, safety. • Treatment: • Arm 1: DOCOX=docetaxel 60 mg/m2 + oxaliplatin 130 mg/m2 on Day 1 of each 21-day cycle. • Arm 2: DOCOX+C = DOCOX with C 400 mg/m2 first dose then 250 mg/m2 weekly • Inclusion: stage IV adenocarcinoma of the GEJ/stomach; measurable disease; ECOG 0-2; and normal renal, hepatic, and marrow function. • Exclusion: Prior Tx other than adjuvant radiation with 5-FU/leucovorin. • Tissue was collected to correlate responses with KRAS status.

  4. Abstract Continued • Results • 150 pts enrolled; 75/arm. • Demographics Arm 1/2: male 79%/80%, median age 61.7/64.0 yrs; disease site: gastric 44%/41%, GEJ 51%/55%, both 5%/4%; 95%/96% had surgery, and 7%/5% had radiation. • Response rates/arm: 26.5%/34.7%. Median PFS: 4.2/5.1 mo (95% C.I. 3.0-5.4 - 4.3-5.9); 1-yr survival: 39.7%/32.4%; median overall survival: 9.0/9.4 mo; median TTR: 1.3/1.4 mo, and median DOR: 7.3/7.2 mo. • AEs: Most frequent Grade 3-4 treatment-related AEs (%) included neutropenia (48.5/43.1), diarrhea (11.8/16.7), febrile neutropenia (13.2/18.1), fatigue (11.8/15.3). Discontinuation due to AEs 21/35 or progressive disease 37/31. AEs were mainly GI, hematologic, or neuropathic. • KRAS:Both treatment regimens seem to be more effective in the wild type KRAS than in the mutated type.

  5. Abstract Continued • Conclusions • The addition of C to DOCOX may improve RR minimally • No significant improvement in PFS, OS, or 1-yr survival • C did not produce clinically significant benefit when added to the backbone of DOCOX. • Toxicities were consistent with the known safety profiles of the study drugs. • Treatment regimens were more effective in wild type than in mutated KRAS • This research was supported, in part, by grants from sanofi-aventis, Bridgewater, NJ, and Lilly/ImClone, Indianapolis, IN.

  6. Study Objectives • Primary Objective • To determine the progression-free survival produced by the combination of docetaxel (Taxotere) + oxaliplatin (Eloxatin) (Arm 1 - DOCOX) versus DOCOX + cetuximab (ERBITUX) (Arm 2 - DOCOX+C) • Secondary Objectives • 1-year survival • Response rate (CR+PR) • Time to response • Duration of response (DOR) • Correlation of KRAS mutation type (mutant vs wild) to response • (in patients with available tissue) • Toxicity

  7. Treatment Schedule Arm 1 Arm 2

  8. Treatment Schedule Continued • *400 mg/m2 on Day 1 of Cycle 1 only; 250 mg/m2 for all other doses. • Cycles continued until disease progression or intolerable toxicity. • Pts were followed for 2 years.

  9. Patient Characteristics (ITT Population)

  10. Results

  11. Results Continued Kaplan-Meier Curves of Progression-Free Survival (PFS) (ITT Population) Median PFS 4.2 5.1

  12. Results Continued Kaplan-Meier Curves of Overall Survival (OS) (ITT Population) Median OS 9.0 9.4

  13. Responses

  14. Responses Continued Kaplan-Meier Curves of Duration of Response (DOR) (Evaluable Population) Median DOR 7.3 7.2

  15. Treatment-Related AEs *Pts received at least 1 dose of study drug.

  16. KRAS Analysis Best Overall Responses by KRAS Status

  17. Conclusions • Addition of C to DOCOX may improve RR minimally. • There appears to be no significant improvement in PFS, OS, or 1-year survival. • C did not produce a clinically significant benefit when added to DOCOX. • Toxicities were consistent with the known safety profiles of the study drug. • DOCOX and DOCOX+C seem to have a greater effect in patients with wild-type versus mutated-type KRAS.

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