Practice Update: Oncology

CONFERENCE COVERAGE 22

ThreeMonths of Oxaliplatin-Based Chemotherapy Usually Suffices, With Less Neurotoxicity Than 6Months, in Stage 3 Colon Cancer A prospective, pooled analysis of nearly 13,000 patients enrolled six phase II trials showed that 6 months of oxaliplatin- based chemotherapy conferred less than 1% added benefit over 3 months. T his outcome of the International Duration Evaluation of Adjuvant chemotherapy (IDEA) was reported confidence interval 0.85–1.06; whereas 3 months of FOLFOX proved inferior to 6 months (hazard ratio 1.16, 95% confidence interval 1.06–1.26). overall study population of stage 3 patients. The clinical conclusion, however, given the reduction in neurotoxicity with a shorter duration of treatment, was that 3 months is almost identical to 6 months.

at the European Society for Medical Oncology (ESMO) 2017 Congress, from September 8–12. Axel Grothey, MD, of the Mayo Clinic, Rochester, Minnesota, explained that since 2004, 6 months of oxaliplatin-based chemotherapy has been the standard of care as adjuvant treatment for stage 3 colon cancer. Oxaliplatin is associated with cumulative neurotoxicities, so a shorter duration of adjuvant therapy could spare toxicity and substantially reduce costs. Dr. Grothey and the IDEA investigators analyzed six concurrently conducted, ran- domized, phase III trials: 1. UK Short Course Oncology Treatment (SCOT) 2. Three Or Six Colon Adjuvant (TOSCA) 3. C80702 4. IDEA France 5. Adjuvant Chemotherapy forcolon cancerwith HIgh EVidencE (ACHIEVE) 6. Hellenic Oncology Research Group (HORG) The noninferiority of 3 vs 6 months of adju- vant folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) was assessed. The primary end- point was disease-free survival, defined as the duration from enrollment to relapse, second colorectal cancer, and death from any cause. Noninferiority was declared when the ratio (3 vs 6 months), estimated by a stratified Cox model, was below 1.12. Noninferiority was examined within subgroups of regi- men and stage as preplanned. The analysis included 12,834 patients from 12 countries, accrued from June of 2007 through 2015. After 3263 (of 3390 expected) disease-free survival events, noninferior for the shorter duration of ther- apy, could not be confirmed for the overall study population (hazard ratio 1.07, 95% confidence interval 1.00–1.15). Noninferiority of 3 vs 6 months was seen for CAPOX (hazard ratio 0.95, 95%

Patients treated with CAPOX suffered from a higher rate of T4 colon cancer (24.3% vs 18.6%, P < .001) than those who received FOLFOX. No significant differences were seen, however, in N-stage, gender, or num- ber of lymph nodes examined. Significant, though small, differences were seen in age and performance sta- tus (1/2). Overall noninferiority results were independent of age (<70, ≥70 years) and gender. Dr. Grothey concluded that the IDEA results provide the basis for individual adjustments of adjuvant treatment duration based on risk of recurrence, patient preference, tox- icity, and the chemotherapy regimen used. Further analyses are warranted to explain the differential performance of CAPOX and FOLFOX with regard to the noninferiority question. The debate on whether to shorten adjuvant chemotherapy for colon cancer from 6 to 3 months took center stage in a special ses- sion at the ESMO 2017 Congress. Alberto Sobrero, MD, of the Ospedale San Martino, Genova, Italy, noted in a written release that study findings were practice-changing. The commonsense conclusion of IDEA is that it’s not worth going through the toxicity and inconven- ience of 6 months to gain less than 1% efficacy. Especially considering that toxic- ity is cut by at least 50% with the 3-month regimen. Dr. Sobrero added that most patients pre- fer the 3-month option, which confers much lower toxicity for very little loss in efficacy. In addition, overall there were minor differ- ences in efficacy between 3 and 6 months, high-risk patients should receive 6 months of chemotherapy. CAPOX should be pre- ferred over FOLFOX. Eric Van Cutsem, MD, of University Hospi- tals Leuven, Belgium, and main author of the ESMO consensus guidelines for the management of patients with metastatic colorectal cancer, noted in the written release that statistically, 3 months of treat- ment was slightly inferior to 6 months in the

He continued, in low-risk patients, the difference was so minor that the clinical conclusion is that 3 months of oxalipla- tin-based chemotherapy is as good as 6 months. Though statistically the differ- ence is small, this makes a huge clinical difference to patients with the reduction in neurotoxicity. Regarding the standard of care for adjuvant chemotherapy in stage 3 colon cancer, Dr. Van Cutsem noted that in high-risk patients, 6 months remains the standard, but in low- risk patients, 3 months should become the new standard duration of treatment. He confirmed that he uses this strategy with his stage 3 colon cancer patients. In high- risk stage 3 patients, he gives 6 months of FOLFOX unless the patient suffers neuro- toxicity, in which case he stops oxaliplatin but continues with fluorouracil for a total of 6 months. In patients with low-risk tumors, he gives 3 months of FOLFOX. www.practiceupdate.com/c/58224

PRACTICEUPDATE ONCOLOGY