Is there a benefit of oxaliplatin in combination with neoadjuvant chemoradiotherapy for locally advanced rectal cancer? An updated meta-analysis: trial

Is there a benefit of oxaliplatin in combination with neoadjuvant chemoradiotherapy for locally advanced rectal cancer? An updated meta-analysis

Phase meta-analysisN = 5,782

Population

Patients with stage II or III rectal cancer in seven randomised trials

Design

Published meta-analysis of published data (PubMed and Cochrane Library screened in May 2021 for trials published to March 2021, plus ESMO, ESTRO, ASCO, ASTRO and ESSO conference abstracts) of randomised trials adding oxaliplatin to preoperative chemoradiotherapy or perioperative chemotherapy for locally advanced rectal cancer: seven trials (ACCORD-12, CAO/ARO/AIO-04, FOWARC, JIAO, NSABP R-04, PETACC-6 and STAR-01, as listed in the open-access full text) with 5782 stage II or III patients, 2727 given oxaliplatin plus fluorouracil and 3055 given fluorouracil alone. The primary endpoint was disease-free survival.

Primary endpoint

DFS

Arms

Fluoropyrimidine alone (control, n = 3,055): Fluorouracil-based or capecitabine-based regimens without oxaliplatin (pooled across the included trials)
Oxaliplatin plus fluoropyrimidine (experimental, n = 2,727): Oxaliplatin added to fluorouracil-based or capecitabine-based regimens (pooled across the included trials)

People

Des Guetz G

DFSHR 0.90 (95% CI 0.81–0.99)OSHR 0.94 (95% CI 0.83–1.06)Δ pCR+3.2 pointsΔ Local recurrence−1.1 points

Show the numbers

Results reported for Is there a benefit of oxaliplatin in combination with neoadjuvant chemoradiotherapy for locally advanced rectal cancer? An updated meta-analysis
Endpoint	Analysis	Oxaliplatin plus fluoropyrimidine	Fluoropyrimidine alone	Effect
DFSSeven randomised trials, 5782 patientsDisease-free survival, pooled hazard ratio of oxaliplatin plus fluorouracil versus fluorouracil alone	exploratoryDes 2021	—	—	HR 0.90 (95% CI 0.81–0.99)P=0.03
OSSeven randomised trials, 5782 patientsOverall survival, pooled hazard ratio of oxaliplatin plus fluorouracil versus fluorouracil alone	exploratoryDes 2021	—	—	HR 0.94 (95% CI 0.83–1.06)P=0.53
pCRSeven randomised trials reporting pCR (5386 patients)Pathological complete response, pooled rates	exploratoryDes 2021	17.9%	14.7%	P=0.002Risk ratio 1.21 (95% CI 1.07-1.37) in the full text; the abstract labels it an odds ratio of 1.21 (1.07-1.37).
Local recurrenceFour randomised trials reporting local recurrence (3635 patients)Local recurrence, pooled rates	exploratoryDes 2021	7%	8.1%	P=0.19Risk ratio 0.86 (95% CI 0.68-1.08), not statistically significant.

Results reported for Is there a benefit of oxaliplatin in combination with neoadjuvant chemoradiotherapy for locally advanced rectal cancer? An updated meta-analysis
Endpoint	Analysis	Oxaliplatin plus fluoropyrimidine	Fluoropyrimidine alone	Effect
DFSSeven randomised trials, 5782 patientsDisease-free survival, pooled hazard ratio of oxaliplatin plus fluorouracil versus fluorouracil alone	exploratoryDes 2021	—	—	HR 0.90 (95% CI 0.81–0.99)P=0.03
OSSeven randomised trials, 5782 patientsOverall survival, pooled hazard ratio of oxaliplatin plus fluorouracil versus fluorouracil alone	exploratoryDes 2021	—	—	HR 0.94 (95% CI 0.83–1.06)P=0.53
pCRSeven randomised trials reporting pCR (5386 patients)Pathological complete response, pooled rates	exploratoryDes 2021	17.9%	14.7%	P=0.002Risk ratio 1.21 (95% CI 1.07-1.37) in the full text; the abstract labels it an odds ratio of 1.21 (1.07-1.37).
Local recurrenceFour randomised trials reporting local recurrence (3635 patients)Local recurrence, pooled rates	exploratoryDes 2021	7%	8.1%	P=0.19Risk ratio 0.86 (95% CI 0.68-1.08), not statistically significant.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
DFS	0.9	0.81–0.99
OS	0.94	0.83–1.06

Appears in

2010 Oxaliplatin with preoperative chemoradiation: four phase 3 trials

Sources

Des Guetz G, Landre T, Bollet MA, Mathonnet M, Quéro L. Is There a Benefit of Oxaliplatin in Combination with Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer? An Updated Meta-Analysis. Cancers (Basel). 2021;13(23).
PubMed DOI