Less can be more for many colorectal cancer patients.
Most patients with stage III colon cancer may be treated with a shorter schedule of adjuvant chemotherapy, according to the results of a large Phase 3 trial. In particular, treatment with 3-month therapy was as effective for patients with low-risk stage III treatment as treatment for 6 months.
A low-risk disease accounts for approximately 60% of stage III colon carcinoma.
The findings were originally presented at the annual meeting of the American Society of Clinical Oncology (ASCO) 2017 and reported at this time by Medscape Medical News . The study has now been published in the New England Journal of Medicine .
The results are changing in practice, commented Richard Schilsky, MD, ASCO's Chief Medical Officer, as the results were presented at the meeting. "I would predict that patients will be prescribed shorter courses of adjuvant chemotherapy in the clinic next week if they have a low-risk colorectal cancer."
ASCO expert Nancy Baxter, MD, from St. Michael's Hospital in Toronto, Ontario, Canada, said: "Less is more."
"This is a great day for patients around the world," she said. "Today, up to 60% of my patients with Stage III colon cancer can stop after 3 months of therapy and be able to continue with their lives and have a lower risk of permanent problems such as numbness of hands and feet."
Based In this study, the National Comprehensive Cancer Network guidelines for colorectal cancer were recently amended to allow patients with stage III colon cancer to be treated at a lower risk with a shorter schedule of adjuvant chemotherapy. 1
Since 2004, standard treatment for stage III colon cancer has been a six-month adjuvant treatment with oxaliplatin plus a fluoropyrimidine. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy would reduce the risk of adverse events and reduce health expenditure.
Led by Axel Grothey, MD of the Mayo Clinic Cancer Center, Rochester, Minn., USA The International Duration Evaluation of Adjuvant Therapy (IDEA) study outlined the results of six prospective studies involving 12,834 patients with stage III colon cancer together. In the parallel Phase 3 trials, non-inferior adjuvant therapy with FOLFOX (fluorouracil), leucovorin and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) was administered for 3 months versus 6 months.
The primary endpoint was disease-free survival at 3 years. Non-inferiority of 3 months of therapy compared to 6 months was achieved when the upper limit of the two-sided 95% confidence interval (CI) did not exceed the hazard ratio (HR) 1.12.
However, after 3263 cases with either recurrence of the disease or death were reported in the cohort, non-inferiority of 3 months treatment versus 6 months could not be confirmed in the total study population (HR 1.07; 95% CI, 1, 00 to 1.15). The 3-year rates of disease-free survival were 74.6% for the 3-month regimen and 75.5% for the 6-month regimen.
Non-inferiority only in subgroups
Non-inferiority of a 3-month regimen was observed in the subgroup of patients treated with the CAPOX regimen (HR, 0.95, 95% CI, 0, 85 – 1.06). The 3-year rates of disease-free survival were 75.9% for the 3-month regimen and 74.8% for the 6-month regimen.
Non-inferiority was not observed in FOLFOX-treated patients. In this subgroup, 6 months of adjuvant therapy was superior to 3 months (HR, 1.16, 95% CI, 1.06-1.26; P = 0.001 for the superiority of 6-month therapy). The difference in the three-year disease-free survival for the two groups was 2.4 percentage points for all combined stages (73.6% vs. 76.0%).
An exploratory analysis of combination treatments for low-risk patients (T1, T2 or T3 and N1 tumors) also found that 3-month regimens were not inferior to 6-month regimens. Disease-free 3-year survival rates were 83.1% and 83.3%, respectively (HR, 1.01, 95% CI, 0.90-1.12).
For patients with high-grade T4 tumors, N2 tumors, or both, the disease-free survival rate for 6-month treatment was superior to that of 3 months (64.4% vs. 62.7%) for the combined treatments (HR , 1.12; 95% CI, 1.03-1.23; P = .01 for superiority).
The 3-month regimen was associated with significantly lower side effects regardless of chemo. This was especially true for neurotoxicity grade 2 or higher. Rates were significantly lower in the 3-month treatment group (16.6% for FOLFOX and 14.2% for CAPOX) than in the 6-month treatment group (47.7% for FOLFOX and 44.9% for CAPOX). The incidence of other events including diarrhea, neutropenia, thrombocytopenia, nausea, mucositis, fatigue, and hand-foot syndrome was also significantly lower with the 3-month regimen.
Better Markers, Less Toxic Treatments
In an accompanying editorial, Schilsky notes that "the enigma of adjuvant chemotherapy for cancer is that the oncologist does not readily recognize the presence or absence of cancer or its response to a single patient Can notice treatment. "
He points out that the tumor never recurs, it remains unclear whether the treatment was effective or unnecessary. "Therefore, the most effective use of adjuvant chemotherapy depends primarily on multi-dimensional risk assessment in each patient."
The results of the current study will help to guide discussions between oncologists and their patients about the complex issues involved with adjuvant therapy. To really optimize the use of this treatment, Schilsky emphasizes, "We need two things: better markers to assess the risk of recurrence and the likelihood of benefit and more effective, less toxic treatments."
"Until we see these two improvements In key areas, the results of the IDEA collaboration provide useful information that helps oncologists discuss the duration of adjuvant therapy that best meets their patients' goals, preferences, and tolerances. "
The IDEA study was funded by grants from the Medical Research Council, the National Institute for Health Research, the National Cancer Institute, the Italian Drug Administration, the Japanese Multidisciplinary Cancer Fund, the French Ministry of Health and the French National Cancer Institute, Dr. Grothey and several co-authors Relations with the Indust disclosed in the original article, and Baxter has not disclosed any relevant financial relationships onships. Dr. Schilsky received grants and non-financial support from AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, Genentech, Merck and Pfizer outside of the submitted work.
N Engl J Med. Published on March 29, 2018. Abstract, Editorial
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