A Randomized Phase 2 Trial of Consolidation Chemotherapy After Preoperative Chemoradiation Therapy Versus Chemoradiation Therapy Alone for Locally Advanced Rectal Cancer: KCSG CO 14-03

Kim, Sun Young; Joo, Jungnam; Kim, Tae Won; Hong, Yong Sang; Kim, Jeong Eun; Hwang, In Gyu; Kim, Beom Gyu; Lee, Moon Hyoung; Kim, Ji Won; Oh, Ho Suk; Ahn, Joong Bae; Zang, Dae Young; Kim, Dae Yong; Oh, Jae Hwan; Baek, Ji Yeon

doi:10.1016/j.ijrobp.2018.04.013

Cited by 51 publications

(74 citation statements)

References 34 publications

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“…Although the pCR rate in this study was lower than reported in both groups (4.9% and 14.3%), consolidation chemotherapy was related to enhanced tumor regression. The pCR rates in our study are lower due to that the patients in our study are unusually adverse in that 65% are cT4 which normally is associated with a low chance of achieving a pCR ( Kim et al, 2018 ). Improved pCR and downstaging rates could be the result of the study treatment, but we cannot exclude that it may also have been affected by a significant delay of surgery in group CCT compared with group nCRT.…”

Section: Discussioncontrasting

confidence: 55%

“…Also, the multivariable analysis which used logistic regression also suggested that the probability of pCR patients was significantly higher in the group CCT compared to the standard treatment group (Odds Ratio = 4.91, 95% CI [1.01– 23.79], P = 0.048 adjusted for cT-stage, cN-stage and categories of time interval) ( Table 4 ). In a randomized phase II clinical trial, Kim et al (2018) implemented a randomized phase II study, which suggested pCR and DS rate could be marginally improved with two cycles XELOX consolidation chemotherapy after preoperative CRT before TME. The interval time between the two groups were both 6–10 weeks but included a difference of only 10 days.…”

Section: Discussionmentioning

confidence: 99%

“…The results showed that adding consolidation chemotherapy after CRT and delaying surgery increased the pCR rate without increasing surgical complications ( Garcia-Aguilar et al, 2015 ; Marco et al, 2018 ). Kim et al (2018) found that pCR and DS rate could be marginally improved with two cycles XELOX consolidation chemotherapy after preoperative CRT before TME. Will the above phase II trials result be the same in the real-world?…”

Section: Introductionmentioning

confidence: 98%

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Consolidation chemotherapy may improve pathological complete response for locally advanced rectal cancer after neoadjuvant chemoradiotherapy: a retrospective study

Cui

Dou

Sun

et al. 2020

PeerJ

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Background Patients with locally advanced rectal cancer (LARC) have an improved prognosis if achieved a pathological complete response (pCR) on account of neoadjuvant chemoradiation therapy (nCRT). However, the proportion of patients achieving pCR is only 8–24%. The purpose of this study was to explore whether the addition of consolidation chemotherapy to nCRT could improve pCR rate in patients with LARC. Materials and Methods The subjects were 144 individuals with clinical stage II (T3–4, N0) or III (any T, N1–2) LARC who had received neoadjuvant CRT followed by total mesorectal excision (TME). Eighty-three patients in the consolidation chemotherapy group received two cycles XELOX between CRT and TME, while 61 patients in the standard treatment group without consolidation chemotherapy. The pCR (ypT0N0), tumor downstaging (ypT0-2N0) after TME and adverse events (AEs) during and post treatment were compared between the treatment groups using multivariable logistic regression analysis. To adjust the unbalanced variables for the primary endpoint, logistic regression analysis and stratified analysis were performed. Results The consolidation chemotherapy group improved pCR rate (19.3% vs 4.9%, p = 0.01) and tumor downstaging rate (45.8% vs 24.6%, p = 0.009) compared to the standard treatment group. After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, patients with consolidation chemotherapy were more likely to reach pCR (adjusted odds ratio 4.91, 95% CI [1.01–23.79], p = 0.048). AEs during and post treatment in the two groups were 54.1% vs 49.3% (p = 0.57), respectively. In addition, the incidence of any grade 1–2 AEs in the two groups was 93.4% vs 95.1% (p = 0.93), while the incidence of grade 3 AEs was 1.6% versus 2.4% (p = 0.74), respectively. No grade 4 AEs occurred in two groups. Conclusions The addition of neoadjuvant consolidation chemotherapy after CRT significantly increased the pCR rate and did not increase the AEs during and post treatment and in patients with LARC.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Consolidation chemotherapy may improve pathological complete response for locally advanced rectal cancer after neoadjuvant chemoradiotherapy: a retrospective study

Cui

Dou

Sun

et al. 2020

PeerJ

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“…Advise: ypT0–1N0 no adjuvant treatment. ypT ≥ 2 or ypN ≥ 1: 6 cycles FOLFOX NR 19 Induction FOLFIRINOX CRT: Capecitabine 50 Gy (25 × 2) 52 Induction FOLFIRINOX CRT: Capecitabine 50 Gy (25 × 2) 51 Induction FOLFIRINOX CRT: Capecitabine 60 Gy (30 × 2) Fokas 37 2019 Germany CAO/ARO/AIO-12 2015–2018 Phase II cT3 < 6 cm from anal verge, cT3b in midrectum (≥ 6 to 12 cm), cT4, or any N+ 2 156 Induction: 5FU + oxaliplatin CRT: 5FU + oxaliplatin 50.4 Gy (28 × 1.8) Not recommended 6–12 150 CRT: 5FU + Oxaliplatin Consolidation: 5FU + oxaliplatin 50.4 Gy (28 × 1.8) Chemoradiotherapy and consolidation chemotherapy versus standard fluoropyrimidine-based chemoradiation Kim 38 2018 South Korea KCSG CO 14-03 2014–2016 Phase II cT3–4 2 55 Capecitabine 50.4 Gy (28 × 1.8) ypStage 0–1: 6 cycles CAP ypStage II–III: 6 cycles CAPOX 6–10 53 CRT: Capecitabine Consolidation: Capecitabine + oxaliplatin 50.4 Gy (28 × 1.8) 8–10 Moore 39 2017 Australia WAIT 2012–2014 Phase III NS 2 24 ...…”

Section: Resultsmentioning

confidence: 99%

“…: CAPOX 50.4 Gy Adj. : ypStage 0–I: 6 × CAP, ypStage II–III: 6 × CAPOX 17 92.5 44 Overall 5 (11.4) 44 8.8 6 (13.6) 39 (88.6) Moore 39 2017 5FU 45 Gy + 5.4 Adj. : – 20.8 91.7 24 NR NR 24 10.6 10 (41.7) 6 (25.0) 22 (91.7) NR NR NR CRT: 5FU Cons.…”

Section: Resultsmentioning

confidence: 99%

Pathological Complete Response Following Different Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis

et al. 2020

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Background Pathological complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) is associated with better survival, less local recurrence, and less distant failure. Furthermore, pCR indicates that the rectum may have been preserved. This meta-analysis gives an overview of available neoadjuvant treatment strategies for LARC and analyzes how these perform in achieving pCR as compared with the standard of care. Methods Pubmed, Embase, and Cochrane Central bibliographic databases were searched. Randomized controlled trials in which patients received neoadjuvant treatment for MRI-staged nonmetastatic resectable LARC were included. The primary outcome was pCR, defined as ypT0N0. A meta-analysis of studies comparing an intervention with standard fluoropyrimidine-based chemoradiation (CRT) was performed. Results Of the 17 articles included in the systematic review, 11 were used for the meta-analysis. Addition of oxaliplatin to fluoropyrimidine-based CRT resulted in significantly more pCR compared with fluoropyrimidine-based CRT only (OR 1.46), but at the expense of more ≥ grade 3 toxicity. Other treatment strategies, including consolidation/induction chemotherapy and short-course radiotherapy (SCRT), did not improve pCR rates. None of the included trials reported a benefit in local control or OS. Five-year DFS was significantly worse after SCRT-delay compared with CRT (59% vs. 75.1%, HR 1.93). Conclusions All included trials fail to deliver high-level evidence to show an improvement in pCR compared with standard fluoropyrimidine-based CRT. The addition of oxaliplatin might result in more pCR but at the expense of more toxicity. Furthermore, this benefit does not translate into less local recurrence or improved survival.

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Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy

Turri,

Ostuzzi,

Vita

et al. 2024

JAMA Netw Open

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ImportanceTreatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates.ObjectiveTo assess the efficacy and tolerability of TNT protocols for LARC.Data SourcesMEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024.Study SelectionRandomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria.Data Extraction and SynthesisTwo authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)–compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach.Main Outcomes and MeasuresThe primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival.ResultsOf 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63).Conclusions and RelevanceIn this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments.

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A Randomized Phase 2 Trial of Consolidation Chemotherapy After Preoperative Chemoradiation Therapy Versus Chemoradiation Therapy Alone for Locally Advanced Rectal Cancer: KCSG CO 14-03

Cited by 51 publications

References 34 publications

Consolidation chemotherapy may improve pathological complete response for locally advanced rectal cancer after neoadjuvant chemoradiotherapy: a retrospective study

Consolidation chemotherapy may improve pathological complete response for locally advanced rectal cancer after neoadjuvant chemoradiotherapy: a retrospective study

Pathological Complete Response Following Different Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis

Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy

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