CHICAGO — Most patients with low-risk stage III colon cancer will likely have their oxaliplatin-based adjuvant chemotherapy regimen cut in half, based on findings of the largest prospective trial on the issue to date, reported here at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting.
The IDEA (International Duration Evaluation of Adjuvant therapy) collaboration pooled results from six prospective studies involving nearly 13,000 patients to show similar efficacy and dramatically reduced side effects with only 3 months compared with 6 months of oxaliplatin and intravenous 5-fluorouracil (FOLFOX) or oral capecitabine (CAPOX) adjuvant therapy.
The result: a consensus statement released by the IDEA investigators "which I hope will make inroads into guidelines in clinical practice," announced IDEA investigator Axel Grothey, MD, from the Mayo Clinic Cancer Center in Rochester, Minnesota, during a press briefing at the meeting.
For the 60% of patients who have low-risk tumors "we do not recommend more than 3 months of chemotherapy with an oxaliplatin-based regimen," he said. "That applies to 20,000 patients per year in the US, and you can easily see that translates to hundreds of thousands of patients worldwide."
"This is a great day for patients throughout the world," commented ASCO expert Nancy Baxter, MD, who is from St Michael's Hospital in Toronto, Ontario, Canada. "Now, today, up to 60% of my patients with stage III colon cancer will be able to stop after 3 months of therapy and be able to get on with their lives and have a lower risk of permanent problems, such as numbness of their hands and feet. Less is more," she said.
The results are practice-changing, added Richard Schilsky, MD, chief medical officer at ASCO. "I would predict that beginning next week in clinic, patients are going to be prescribed shorter courses of adjuvant chemotherapy if they have a low-risk colon cancer."
"This is an important advance with major clinical impact," Wafik S. El-Deiry, MD, PhD, from Fox Chase Cancer Center, Philadelphia, Pennsylvania, told Medscape Medical News. "It will be a welcome change to only need to get 3 months of oxaliplatin-containing adjuvant therapy. People will experience less long-lasting neurotoxicity and will be able to resume their normal lives sooner."
For more than a decade, standard treatment for stage III colon cancer has been associated with dose-dependent oxaliplatin-related neurotoxicity, such as nerve damage, numbness, tingling, and pain, "which can really persist for the rest of the patient's life," noted Dr Grothey.
But investigating the risks and benefits of shorter treatment duration was a daunting prospect.
"What we're really talking about here is balancing less toxicity with a potential for higher risk of recurrence. We needed a high number of patients to really have a precise estimate," he said.
Funding for such an undertaking could not come from industry. "Who is interested in shortening the duration of therapy from a commercial perspective?" Instead, funding came from the National Institutes of Health (NIH). "These trials, which have immediate impact for patient care, which are critical for patient care, can only be conducted with a publicly funded clinical trial system," he said.
"This study is a great example of how NIH funding can have a major and immediate impact on the lives of cancer patients," agreed Dr Baxter.
Details of the Results
The study randomly assigned 12,834 patients to 6 or 3 months of FOLFOX or CAPOX based on clinician/patient choice (this was not a comparison of the two regimens) to examine noninferiority of the shorter regimen.
It showed a dramatic reduction of neurotoxicity with 3 months of treatment (FOLFOX, 17%; CAPOX, 15%) compared with 6 months (48% and 45%, respectively; P < .0001).
"There was three times more toxicity with 6 months compared to 3 months, which was highly statistically significant," said Dr Grothey.
However, the efficacy analysis, based on 3-year disease-free survival, just failed to meet the prespecified noninferiority threshold, defined as an upper hazard ratio limit of 1.12.
"When you do the math, we compromise, we potentially reduce disease-free survival by 0.9% at 3 years. Noninferiority was not achieved, but the difference in efficacy is very small," he said.
Subgroup analysis of low- and high-risk groups based on tumor stage and lymph node involvement showed that 3 months of treatment was adequate for patients with a low- but not a high-risk tumor burden.
"For the high-risk patient I think we can make an assessment based on tolerability of therapy, patient preference, risk of recurrence, and choice of therapy," he said.
However, when analyzed by treatment type, "it seems that 3 months of CAPOX was adequate for all patients regardless of stage, whereas with FOLFOX you needed 6 months of therapy for high-risk tumors."
Table. Three-Year Disease-Free Survival
|Subgroup||3 Months of Treatment (%)||6 Months of Treatment (%)|
Dr El-Deiry commented: "It will be important to remember that the results apply to T1-3N1 colon cancer and not T4 or N2 disease or after curative surgery for metastatic stage IV disease. The results are about colon cancer and not rectal cancer, whereas in the past both have generally been treated similarly in the adjuvant setting for stage III disease. It is also important to remember that the findings are about oxaliplatin-containing adjuvant therapy and not 5-fluorouracil or capecitabine adjuvant monotherapy. There are many patients, including older patients, who receive monotherapy with 5-fluorouracil or capecitabine, and for those patients this study will not justify reduction to 3 months of adjuvant therapy for colon cancer even if they have T1-3N1 disease."
The IDEA study was funded by grants from the Medical Research Council, National Institute for Health Research, National Cancer Institute, Italian Agency for Drugs, Japanese Foundation for Multidisciplinary Treatment of Cancer, French Ministry of Health, and French National Cancer Institute. Dr Grothey reports a consulting or advisory role (institutional) with Genentech/Roche, Bayer, Sanofi, Bristol-Myers Squibb, Lilly, Boston Biomedical, Amgen; travel, accommodations, and expenses from Genentech/Roche, Bayer, Bristol-Myers Squibb, Boston Biomedical, Amgen, Boehringer Ingelheim; and research funding (institutional) from Genentech/Roche, Bayer, Pfizer, Eisai, Sanofi, Lilly, Boston Biomedical, and Boehringer Ingelheim. Dr Baxter and Dr El-Deiry have disclosed no relevant financial relationships.
American Society of Clinical Oncology (ASCO) 2017 Annual Meeting. Abstract LBA1. Presented June 4, 2017.
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Cite this: Less Is More: Patients With Colon Cancer Get a Chemo Break - Medscape - Jun 04, 2017.