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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
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%
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).
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
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.
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.
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