Dakhil, Shaker R.

453 Background: A 12-gene assay (Oncotype DX Colon Cancer) has been clinically validated as a predictor of recurrence risk in stage 2 colon cancer patients following surgery. We conducted the first prospective study to characterize the impact of Recurrence Score results on medical oncologists’ recommendations regarding adjuvant chemotherapy in T3, Mismatch Repair-proficient (MMR-P) stage 2 colon cancer patients. Methods: Consecutive patients with resected stage 2A colon cancer who were candidates for adjuvant chemotherapy were consented and enrolled by 105 medical oncologists from 17 sites in the Mayo Clinic Cancer Research Consortium. Each patient’s tumor specimen was assessed by the Recurrence Score test (quantitative RT-PCR) and MMR (IHC). Prior to and after receiving these results, physicians completed surveys indicating their planned treatments given hypothetical or known MMR results, recorded as Observation (Obs), 5FU-based chemotherapy (5FU), or 5FU + Oxaliplatin (Oxal). Change in treatment recommendation intensity from baseline to follow-up was defined as: increased if change from Obs to 5FU +/- Oxal or from 5FU to 5FU+Oxal, decreased if change from 5FU + Oxal to 5FU or Obs, or from 5FU to Obs, or no change. Results: 187 of 221 patients enrolled were evaluable including 141 who were MMR-P (avg age 63, 65% ECOG PS 0, med tumor size 5 cm, 11% high grade, 91% with 12+ nodes examined). In the primary analysis treatment recommendations changed for 63 (45%) of 141 MMR-P patients, with intensity decreasing for 47 (33%) and increasing for 16 (11%). Recommendations for chemotherapy (5-FU +/- Oxal) decreased from 73 (52%) patients pre-assay to 42 (30%) post-assay. Increased treatment intensity was more likely at higher Recurrence Score values and decreased intensity at lower Recurrence Score values (p=0.011), and any change was more likely when MMR status was unknown at baseline (p = 0.041). Conclusions: In this prospective study, quantitative recurrence risk information provided by the Recurrence Score test was associated with treatment recommendation changes for 45% of T3 MMR-P stage II colon cancer patients. Use of the 12-gene assay may lead to overall reductions in chemotherapy.

391 Background: Prior economic analysis of a 12-gene assay (Oncotype DX), compared with patterns of care reported in the NCCN database of patients with stage II, T3, DNA mismatch repair proficient (MMR-P) colon cancer, predicted that the assay would save medical costs and improve patient well-being (Hornberger et al., Value Health, 2012). This study assessed the validity of those findings with actual adjuvant chemotherapy (aCT) recommendations. Methods: Outcomes and costs were estimated for patients with stage II, T3, MMR-P colon cancer using a Markov model. A study of 141 patients from 17 sites in the Mayo Clinic Cancer Research Consortium collected data on aCT recommended before and after knowledge of the 12-gene assay results (Srivastava et al. abstract). Quality-adjusted life years (QALY) and medical resource use after recurrence were computed using guideline-validated state-transition probability estimation methods. Risk of progression and incidence of adverse events with different aCT regimens were based on published literature. Drug and administration costs for aCT were obtained from 2012 Medicare fee schedules. One-way sensitivity analyses were conducted to evaluate parameter influence on economic impact. Results: After receiving the 12-gene assay results, physician recommendations in favor of aCT decreased 22% (95% CI 11%-32%; McNemar test p<0.001) from 73 (52%) to 42 (30%) patients. Oxaliplatin aCT and 5-FU monotherapy recommendations each declined 11%. Average aCT costs decreased $5,738 for drugs, $668 for administration, and $3,268 for adverse events management. Overall, average total direct medical costs decreased $4,203. The net effect on average patient well-being was a gain of 0.083 QALYs. Total medical costs are most influenced by change in aCT recommendations, 5-FU monotherapy efficacy, and oxaliplatin drug acquisition cost. Savings are expected to persist even if the cost of oxaliplatin dropped by >75% due to generic substitution. Conclusions: The 12-gene assayhas been shown to alter aCT recommendations for patients with stage II, T3, MMR-P colon cancer. This study provides real-world confirmation that these changes in aCT reduce direct medical costs and improve patient well-being.

PURPOSE: To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia. PATIENTS AND METHODS: Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 2.5 mg twice a day plus placebo, or (3) both agents. Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight. RESULTS: Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status. A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P = .0001) for appetite and 11% versus 3% (P = .02) for ≥ 10% baseline weight gain. Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone. The Functional Assessment of Anorexia/Cachexia Therapy questionnaire, which emphasizes anorexia-related questions, demonstrated an improvement in quality of life (QOL) among megestrol acetate–treated and combination-treated patients. The single-item Uniscale, a global QOL instrument, found comparable scores. Toxicity was also comparable, with the exception of an increased incidence of impotence among men who received megestrol acetate. CONCLUSION: In the doses and schedules we studied, megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone. Combination therapy did not appear to confer additional benefit.

271 Background: Epidermal growth factor inhibitors show some benefit in the treatment of advanced pancreatic cancer. A trial to evaluate the incorporation of Pmab into a conventional multimodality regimen and continuation as maintenance therapy was conducted in pts with LA disease. Methods: Pts with ECOG PS 0-1, preserved organ function and tumor encompassed within standard radiation fields were eligible. Pmab 6 mg/kg on days 1, 15, 29 and continuous infusion 5-FU 225 mg/m2/d or capecitabine 825 mg/m2 were given with RT. Pts then received weekly gemcitabine 1000 mg/m2 and Pmab on days 1, 15 for three 4-week cycles. Maintenance Pmab was then continued for additional 6 months. RT consisted of 45 Gy to the tumor and regional nodes with a 5.4 Gy boost using conformal techniques. Primary endpoint of one-year survival (OS) with secondary endpoints progression-free survival (PFS), confirmed tumor response, and adverse events (at least possibly related) are reported. Results: 51 pts (23 M: 28 F) were enrolled with a median age of 65 (range: 43-84). Twenty-two pts (43%) received at least 1 cycle of post-chemo-RT, while 29 patients only received chemo-RT. All 51 pts have ended treatment with pts going off study because of: progression (39%), adverse events (27%), refusal (25%), and other reasons (8%). Frequently occurring maximum grade 3/4 AEs across the entire treatment course (chemo-RT + post-chemo-RT chemo) are shown below. With a median follow-up of 12.3 months, survival at 12 months is 50.2% (95% CI: 37.9-66.5%), median survival 12.1 mos (95% CI: 6.8-15.9) and median PFS 7.4 mos (95% CI: 3.7-8.6). Confirmed response rate was 5.9% (1-CR, 2-PR). Conclusions: The addition of Pmab to a conventional chemo-RT regimen provides benefit in terms of median survival. This is similar to reports of other EGFR inhibitors in LA disease. Adverse events, especially during the chemo-RT portion, were considerable and affected administration of subsequent systemic maintenance therapy. [Table: see text]

CRA9015 Background: Hot flashes are a common symptom during the menopause transition or following breast cancer treatment that can negatively impact the quality of life for many women. Preliminary data have suggested that flaxseed, a rich source of dietary lignans, may be a potentially effective treatment for hot flashes. Methods: A phase III randomized, placebo controlled trial was conducted to evaluate the efficacy of flaxseed in reducing hot flashes. Postmenopausal women were randomly assigned to a flaxseed bar (providing 410 mg of lignans) for 6 weeks vs a placebo bar. Participants completed daily prospective, self report hot flash diaries during the baseline week and then began eating one study bar per day for 6 weeks, while continuing to record their daily hot flashes. The intra-patient difference in hot flash activity between baseline and the last treatment week was the primary endpoint. Side effects of the bars were evaluated through self report and CTC assessment. Results: Between October and December 2009, 188 women were enrolled onto this trial. Mean hot flash scores were reduced by 4.9 units in the flaxseed group and 3.5 in the placebo group (p=0.29). In both groups, a little over a third of the women received a 50% reduction in their hot flash scores. Only one side effect was significantly different between groups, that being grade 1 pruritis, which was more common (7%) in the placebo group versus 1% in the flaxseed group. Both groups reported increased abdominal distension, flatulence, diarrhea and nausea. Adherence and ability to detect treatment assignment did not differ between groups. Conclusions: The results of this trial do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were likely due to the fiber content in the flaxseed and placebo bars.