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First-line chemotherapy
combined with cetuximab
or bevacizumab for KRAS
wild-type advanced or
metastatic colorectal cancer
JAMA: The Journal of the American Medical Association
Take-home message
•
This study evaluated the addition of cetuximab versus bevacizumab
to FOLFOX6 or FOLFIRI in 1137 patients with previously untreated
advanced or metastatic KRAS wild-type colorectal cancer. Median OS
was 30.0 months in the cetuximab-chemotherapy group and 29.0 months
in the bevacizumab-chemotherapy group (HR, 0.88; P = 0.08). Median PFS
was 10.5 months in the cetuximab-chemotherapy group and 10.6 months
in the bevacizumab-chemotherapy (HR, 0.95; P = 0.45). Response rates
were not significantly different for cetuximab and bevacizumab (59.6%
vs 55.2%, respectively; difference, 4.4%; P = 0.13).
•
There is no significant difference between the addition of cetuximab
or bevacizumab to chemotherapy with regard to OS or PFS in patients
with untreated advanced or metastatic KRAS wild-type colorectal cancer.
Abstract
IMPORTANCE
Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic
drugs provides clinical benefit to patients with advanced or metastatic colorectal can-
cer, but the optimal choice of the initial biologic therapy in previously untreated patients
is unknown.
OBJECTIVE
To determine if the addition of cetuximab vs bevacizumab to the combination
of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of
leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy
in advanced or metastatic KRAS wild-type (wt) colorectal cancer.
DESIGN, SETTING, AND PARTICIPANTS
Patients (≥18 years) enrolled at community and
academic centers throughout the National Clinical Trials Network in the United States
and Canada (November 2005–March 2012) with previously untreated advanced or
metastatic colorectal cancer whose tumors were KRAS wt chose to take either the
mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized
to receive either cetuximab (n=578) or bevacizumab (n=559). The last date of follow-up
was December 15, 2015.
INTERVENTIONS
Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI
chemotherapy regimen chosen by the treating physician and patient.
MAIN OUTCOMES AND MEASURES
The primary end point was overall survival. Secondary
objectives included progression-free survival and overall response rate, site-reported
confirmed or unconfirmed complete or partial response.
RESULTS
Among 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of
patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviv-
ing patients was 47.4 months (range, 0–110.7 months), and 82% of patients (938 of 1137)
experienced disease progression. The median overall survival was 30.0 months in the
cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy
group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77–1.01; P=0.08). The median
progression-free survival was 10.5 months in the cetuximab-chemotherapy group and
10.6 months in the bevacizumab-chemotherapy group with a stratified HR of 0.95 (95%
CI, 0.84–1.08; P=0.45). Response rates were not significantly different, 59.6% vs 55.2%
for cetuximab and bevacizumab, respectively (difference, 4.4%, 95% CI, 1.0–9.0%, P=0.13).
CONCLUSIONS AND RELEVANCE
Among patients with KRAS wt untreated advanced or met-
astatic colorectal cancer, there was no significant difference in overall survival between
the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment.
Effect of first-line chemotherapy combined with cetuximab or bevacizumab on over-
all survival in patients with KRAS wild-type advanced or metastatic colorectal cancer:
a randomized clinical trial.
JAMA
2017 Jun 20;317(23)2392-2401, AP Venook, D Nied-
zwiecki, HJ Lenz, et al.
Clinical implications of
monitoring circulating
tumor DNA in patients
with colorectal cancer
Clinical Cancer Research
Take-home message
•
This longitudinal cohort study was designed
to evaluate the predictive value of circu-
lating tumor DNA (ctDNA) for recurrence
in 45 patients who underwent resection
for colorectal cancer. A total of 371 plasma
samples were analyzed. Samples from 27
patients were positive for ctDNA postop-
eratively in the 14 who had relapsed but in
none of the non-relapsing patients. Relapse
was detected at a lead time of 9.4 months
compared with detection using CT imaging.
The ctDNA levels appeared to correlate with
changes in tumor volume.
•
The authors concluded that ctDNA serves
as a reliable marker of residual disease and
identifies patients at very high risk of relapse.
Abstract
PURPOSE
We investigated if detection of circulating tumor
DNA (ctDNA) after resection of colorectal cancer (CRC)
identifies the patients with the highest risk of relapse, and
furthermore, whether longitudinal ctDNA analysis allows
early detection of relapse and informs about response
to intervention.
EXPERIMENTAL DESIGN
In this longitudinal cohort study we
used massively parallel sequencing to identify somatic
mutations and used these as ctDNA markers to detect
minimal residual disease and to monitor changes in tumor
burden during a three year follow-up period.
RESULTS
A total of 45 patients and 371 plasma samples
were included. Longitudinal samples from 27 patients
revealed ctDNA post-operatively in all relapsing patients
(n=14), but not in any of the non-relapsing patients. ctDNA
detected relapse with an average lead-time of 9.4 months
compared to CT imaging. Of 21 patients treated for local-
ized disease, six had ctDNA detected within 3 months
post-surgery. All six later relapsed compared to four of
the remaining patients (Hazard ratio (HR), 37.7, 95% con-
fidence interval (CI), 4.2–335.5; P<0.001). The ability of a
3 month ctDNA analysis to predict relapse was confirmed
in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5–15.7;
P=0.007). Changes in ctDNA levels induced by relapse
intervention (n=19) showed good agreement with changes
in tumor volume (Kappa=0.41, Spearman’s rho=0.4).
CONCLUSIONS
Postoperative ctDNA detection provides
evidence of residual disease and identifies patients at
very high risk of relapse. Longitudinal surveillance enables
early detection of relapse and informs about response to
intervention. These observations have implications for the
post-operative management of CRC patients.
Clinical implications of monitoring circulating tumor DNA
in patients with colorectal cancer.
Clin Cancer Res
2017
Jun 09;[EPub Ahead of Print], LV Schøler, T Reinert, MW
Ørntoft, et al.
COLON & RECTUM
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