scholarly journals Rationale and design of the POLEM trial: avelumab plus fluoropyrimidine-based chemotherapy as adjuvant treatment for stage III mismatch repair deficient or POLE exonuclease domain mutant colon cancer: a phase III randomised study

ESMO Open ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. e000638 ◽  
Author(s):  
David Lau ◽  
Eleftheria Kalaitzaki ◽  
David N Church ◽  
Hardev Pandha ◽  
Ian Tomlinson ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mismatch Repair ◽  
Early Stage ◽  
Randomised Trial ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Colon Cancers ◽  
Exonuclease Domain ◽  
The Uk

Background10%–15% of early-stage colon cancers harbour either deficient mismatch repair (dMMR), microsatellite instability high (MSI-H) or POLE exonuclease domain mutations, and are characterised by high tumour mutational burden and increased lymphocytic infiltrate. Metastatic dMMR colon cancers are highly sensitive to immune checkpoint inhibition, and recent data show POLE-mutant tumours are similarly responsive. We are conducting a phase III randomised trial to determine if the addition of the anti-PD-L1 antibody avelumab following adjuvant chemotherapy improves disease-free survival (DFS) in patients with stage III dMMR/MSI-H or POLE mutant colon cancer and is a cost-effective approach for the UK National Health Service (NHS).MethodsWe are recruiting patients with completely resected, stage III colon cancer confirmed to have dMMR/MSI-H, locally or POLE exonuclease domain mutation on central testing. Eligible patients are randomised in a 1:1 ratio to standard fluoropyrimidine-based chemotherapy (capecitabine, oxaliplatin for 12 weeks or capecitabine for 24 weeks) or chemotherapy, followed by avelumab (10 mg/kg, 2 weekly for 24 weeks). Stratification is by chemotherapy received and MMR/MSI-H status. The primary endpoint is DFS. Secondary endpoints include overall survival, toxicity, quality of life and health resource use. The 3-year DFS rate in the control arm is expected to be ~75%. Avelumab is expected to improve the 3-year DFS rate by 12% (ie, 87%). Target accrual is 402 patients, which provides 80% power to detect an HR of 0.48 for DFS at a two-sided alpha of 0.05. This national, multicentre phase III trial is sponsored by the Royal Marsden NHS Foundation Trust and it is anticipated that approximately 40 centres in the UK will participate. This study opened to recruitment in August 2018.Trial registration numberNCT03827044

POLEM: Avelumab plus fluoropyrimidine-based chemotherapy as adjuvant treatment for stage III dMMR or POLE exonuclease domain mutant colon cancer—A phase III randomized study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS3615-TPS3615 ◽  
Author(s):  
David Lau ◽  
David Cunningham ◽  
Angela Gillbanks ◽  
Richard Crux ◽  
Rachel Powell ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Randomized Study ◽  
Randomised Trial ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Colon Cancers ◽  
Metastatic Setting ◽  
Exonuclease Domain

TPS3615 Background: Colon cancer with deficient mismatch repair (dMMR) and POLE mutations are characterised by a high tumor mutational burden (TMB) and an immunogenic lymphocyte infiltrate. Approximately 12% of stage III colon cancer have dMMR. POLE mutations occur in 1% of colon cancers, but is enriched in patients <50 years of age. Colon cancer with high TMB have demonstrated to be sensitive to immune checkpoint inhibition in the metastatic setting. We are conducting a phase III randomised trial to determine if the addition of the anti-PD-L1 antibody, avelumab following adjuvant chemotherapy can improve disease free survival (DFS) in patients with stage III colon cancer with dMMR or POLE mutations. Methods: We are recruiting patients with curatively resected, stage III colon cancer which are dMMR or have a centrally confirmed POLE exonuclease domain mutation. Eligible patients are randomised in a 1:1 ratio to standard fluoropyrimidine-based chemotherapy (CAPOX [capecitabine, oxaliplatin] for 12 weeks or capecitabine for 24 weeks) or chemotherapy followed by avelumab (10mg/kg, 2 weekly for 24 weeks). Stratification is by chemotherapy received and MMR status. The primary endpoint is DFS. Secondary endpoints include overall survival, toxicity, quality of life, and health resource use. Exploratory objectives will investigate circulating, tumor and stool based biomarkers of avelumab benefit. The 3-year DFS rate in the control arm is expected to be ~75%. Avelumab is expected to improve the 3-year DFS rate by 12% (i.e. 87%). Target accrual is 402 patients which provides 80% power to detect a hazard ratio of 0.48 for DFS at a two–sided alpha of 0.05. This trial is a national, multi-centre phase III trial and it is anticipated that approximately 40 centres in the UK will participate. This study opened to recruitment in August 2018. Clinical trial information: NCT03827044.

Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial

2018 ◽  
Vol 36 (15) ◽  
pp. 1469-1477 ◽  
Author(s):  
Thierry André ◽  
Dewi Vernerey ◽  
Laurent Mineur ◽  
Jaafar Bennouna ◽  
Jérôme Desrame ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Health Care Providers ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Care Providers ◽  
Free Survival ◽  
Stage Iii Colon Cancer ◽  
Disease Free

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

QIM19-124: Does Virtual Navigation Improve Care Continuity and Compliance in Patients With Early Stage Colon Cancer?

2019 ◽  
Vol 17 (3.5) ◽  
pp. QIM19-124
Author(s):  
Dayna Crawford ◽  
Brook Blackmore ◽  
Jeremy Ortega ◽  
Erica Williams
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Stage I ◽  
Stage Iii ◽  
Nccn Guidelines ◽  
Care Continuity ◽  
Colon Cancers ◽  
Follow Up Care

Background: Colon cancer is the 3rd most common cancer in men and women combined, with an occurrence rate of 4.49% for men and 4.15% for women. The 2018 expectation is 50,630 deaths related to colon cancer in the United States (American Cancer Society Facts and Figures 2018). Early detection is increasing with nearly 45% of colon cancers diagnosed as stage I/II (Sarah Cannon Cancer Registry 2015). Treatment for early stage I/II colon cancer patients usually involves surgery then surveillance. On-site navigators perform their duties by patient need and barriers to care. Late stage III/IV colon cancer patients require more assistance and face more barriers, which often leaves early stage I/II patients without an advocate. This disparity can lead to lower rates of follow-up care for early stage I/II patients. Sarah Cannon created a program for virtual colon navigation (VCN) to determine if early stage I/II patients benefit from a virtual navigator who offers support by phone throughout their disease process. Objectives: The goal was to increase early stage I/II patients’ knowledge of their cancer and convey the importance of compliance with follow-up care, such as repeat colonoscopy as recommended by their physician and NCCN Guidelines. Methods: By developing software that utilizes artificial intelligence, Sarah Cannon created an automated process to identify colon cancer patients at the time of diagnosis. This technology then routes positive pathology reports to a VCN who contacts the early stage I/II patients by telephone, ensuring patient connection to the suitable physician for treatment. The VCN helps patients understand their diagnosis, provides education, assesses barriers to care, connects to resources, provides emotional support, and offers assistance with follow-up for physician visits, imaging and procedures such as colonoscopies, based upon NCCN Guidelines and physician guidelines. The VCN also connects stage III/IV patients with an on-site navigator in their region for more hands-on navigation. Results: Through September 2018, Sarah Cannon navigated 734 colon cancers, 332 stage I/II and 402 stage III/IV. With our increased capacity, Sarah Cannon/HCA maintained a 98% rate of follow-up care with new diagnoses of all stages of colon cancer. Conclusions: The VCN program allowed Sarah Cannon/HCA to improve care continuity and compliance based upon NCCN Guidelines for early stage I/II colon cancer patients throughout 5 regions and 37 facilities.

Adjuvant FOLFIRI with or without cetuximab in patients with resected stage III colon cancer: NCCTG Intergroup phase III trial N0147.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 363-363 ◽  
Author(s):  
J. Huang ◽  
D. J. Sargent ◽  
M. R. Mahoney ◽  
S. N. Thibodeau ◽  
T. C. Smyrk ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Clin Oncol ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Stage Iii Colon Cancer ◽  
Kras Status ◽  
Secondary Endpoints ◽  
Resected Stage

363 Background: Irinotecan (CPT-11) has demonstrated antitumor activity against metastatic colorectal cancer used alone or with 5-fluorouracil (5FU)/leucovorin (LV). Two arms with CPT-11, 5FU, and LV (FOLFIRI) +/- cetuximab (Cmab) were originally included in N0147. However, after CALGB 89803 (J Clin Oncol. 25:3456, 2007), PETACC-3 (J Clin Oncol. 27:3117, 2009), and Accord02 (Ann Oncol. 20:674, 2009) showed no benefit to the three-drug combination in adjuvant therapy, the CPT-11 arms of N0147 were discontinued. We report the outcomes for patients given FOLFIRI +/- Cmab. Methods: Following a signed informed consent patients with resected stage III colon cancer were randomized to one of 6 arms including 12 biweekly cycles of CPT-11 180 mg/m2 d1 with LV 400 mg/m2, 5FU 400 mg/m2 bolus IV, then 46-hr IV 5FU 2,400 mg/m2 on d1-2 without (Arm B, FOLFIRI) or with Cmab (Arm E) 400 mg/m2 d1 cycle 1 then Cmab at 250 mg/m2 d1 and 8. Primary endpoint was 3-year disease-free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Results: 156 patients (Arm B-111, Arm E-45) were enrolled; median follow-up on 81 patients in Arm B was 60.3 months and 58.2 months in Arm E for 41 patients. wtKRAS (vs mt) status was associated with improved DFS (HR=0.6 [95% CI 0.4-1.1], p = 0.09) and OS (HR 0.7 [95% CI 0.4-1.5], p = 0.38). The addition of Cmab improved DFS and OS in the overall group and within wtKRAS pts. Grade greater than III non-hematologic adverse effects were significantly increased in the Cmab arm (46% vs. 64%, p = 0.05). Conclusions: In this randomized phase III trial adjuvant FOLFIRI resulted in a 3-year DFS lower than that expected for FOLFOX. Trends for improved DFS and OS with the addition of Cmab were observed in patients with resected stage III colon cancer patients, regardless of KRAS status. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer. [Table: see text] [Table: see text]

Six months versus twelve months of capecitabine as adjuvant chemotherapy for stage III (Dukes' C) colon cancer: Initial safety report for the open-label randomized phase III study (JFMC37-0801).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3607-3607 ◽  
Author(s):  
Katsuyuki Kunieda ◽  
Sotaro Sadahiro ◽  
Hideyuki Mishima ◽  
Chikuma Hamada ◽  
Shigetoyo Saji ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Treatment Duration ◽  
Disease Free Survival ◽  
Chemotherapeutic Agents ◽  
Phase Iii ◽  
Stage Iii ◽  
Serious Adverse Events ◽  
Phase Iii Trial ◽  
Stage Iii Colon Cancer

3607 Background: The standard treatment duration of adjuvant chemotherapy (CT) in patients (pts) with stage III colon cancer is 6 months. On the other hand, no clinical trial showed the optimal treatment duration of oral chemotherapeutic agents in adjuvant setting for colon cancer. Sargent et al have reported that 83% of recurrences in stage II and III pts have occurred within the first 3 years after surgery and peak was observed around one year after surgery. Therefore, to clarify the benefit of 12 months administration of Capecitabine, we designed randomized phase III trial for a comparison of 6 months treatment and 12 months treatment of capecitabine as adjuvant CT for stage III colon cancer. Methods: JFMC37 is a multicenter, randomized Phase III trial. Patients with fully resected Stage III colon or recto sigmoid cancer were eligible. Capecitabine was administered orally as tablets, 2,500 mg/m²/day for 14 days followed by a 7-days rest. Treatment is continued to 8 cycles (6 months) in arm A (A) or 16 cycles (12 months) in arm B (B). Patients were randomized 1:1 to A or B. Data size was estimated by disease free survival as primary endpoint. The statistical design is based on superiority hypothesis; 5-yrs DFS is 60% in arm A, 67% in arm B ;unilateral α=0.05, 1-β=0.8;and planed accrual is 1200 pts. Results: Between September 2008 to December 2009, 1304 patients were enrolled and then randomized. Both arms were well balanced for mean age: (A) 64.1, (B) 63.8; ECOG PS (%0/1): (A) 95.0/5.0, (B) 97.1/2.9; involvement of lymph nodes (%N0/N1/N2): (A) 77.1/19.9/3.1, (B) 76.6/19.7/3.7. Treatment completion rate for A and B were 68.2% and 43.4%. Incidences of serious adverse events (SAEs) over 1% were neutropenia: (A) 2.6%, (B) 3.8%, diarrhea: (A) 2.9%, (B) 2.1%, loss of appetite: (A) 1.3%, (B) 1.0%, fatigue: (A) 1.8%, (B) 1.2%, hand-hoot syndrome: (A) 16.4%, (B) 22.1%. Conclusions: There were no obvious differences in SAEs between arm A and arm B. Although twelve months of capecitabine showed a tendency to increase G3/4 hand-foot syndrome, we concluded that incidence of SAEs were acceptable and comparable to previously report.

Chemotherapy treatment patterns for early-stage breast cancer (ESBC): Decreasing use of anthracycline-based regimens.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 141-141
Author(s):  
Katherine M. Serrurier ◽  
Jimmy Hwang ◽  
Joseph P. McGuire ◽  
Ann C. Griffin ◽  
Michelle E. Melisko ◽  
...  
Keyword(s):  
Cancer Registry ◽  
Early Stage ◽  
Prospective Trial ◽  
Marked Change ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Publication Date ◽  
Time Periods ◽  
The Impact

141 Background: Anthracyclines (A), given in sequence or combination with other agents, have been the mainstay of adjuvant chemotherapy (CTX) for ESBC for more than two decades. Recent molecular studies have questioned the value of A for lower risk disease. A single prospective trial presented in 2005 and published in 2006 (Jones et al) compared docetaxel and cyclophosphamide (TC) to doxorubicin and cyclophosphamide and reported improved disease free survival (2006) and overall survival (2009) with TC. We sought to understand the impact of this study on the type of CTX regimens used to treat ESBC. Methods: Using the UCSF Cancer Registry database and including patients who received at least one cycle of CTX at UCSF, we recorded use of A or non-anthracycline (NA) based CTX regimens in women with ESBC and correlated type of CTX with tumor stage, receptor status, and age. Based on the publication date of TC we looked at the use of A versus NA based CTX during two time periods, 2000-2005 and 2006-2010. Results: 1,116 patients met criteria for inclusion; 17 were excluded due to inadequate information. Patient characteristics were: median age 49 (range 21-78), stage I (24%), stage II (56%), and stage III (20%), 50% hormone receptor (HR) +, 25% HER2 +, 17% HR-/HER2-. From 2000-2010, 80% received A CTX. Overall use of A decreased from 95% to 65%, while use of NA based CTX increased from 5% to 35%. The table compares use of NA CTX during the two time periods by clinical variables. Conclusions: Use of NA CTX increased significantly over the 2nd half of the last decade in all cases except those patients with stage III disease. The timing of this marked change correlates with publication of TC, and emphasizes the impact of positive phase III trials on treatment practice. This study was supported by the UCSF Cancer Registry. [Table: see text]

A randomized phase III trial of S-1/oxaliplatin (SOX) versus UFT/leucovorin as adjuvant chemotherapy for high-risk stage III colon cancer: The ACTS-CC 02 trial.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 484-484 ◽  
Author(s):  
Takao Takahashi ◽  
Eiji Sunami ◽  
Tetsuya Kusumoto ◽  
Mitsuyoshi Ota ◽  
Yoshiyuki Sakamoto ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Primary Endpoint ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Disease Stage ◽  
Stage Iiic ◽  
Stage Iii Colon Cancer

484 Background: The ACTS-CC 02 trial was designed to verify the superiority of postoperative adjuvant chemotherapy with S-1/oxaliplatin (SOX) over UFT/leucovorin (LV), one of the standard oral fluoropyrimidine regimens in Japan, in terms of disease-free survival (DFS) in patients (pts) with high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). The results of the safety analysis have been reported previously (Clin Colorectal Cancer, 2018). We now present the 3-year DFS results as the primary endpoint. Methods: Pts who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300–600 mg/day of UFT according to body surface area [BSA] and 75 mg/day of LV on days 1-28, every 35 days, 5 courses) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80–120 mg/day of S-1 according to BSA on days 1-14, every 21 days, 8 courses). The primary endpoint was DFS. Results: From April 2010 through October 2014, a total of 966 pts were enrolled at 260 institutions. The full analysis set, excluding pts who withdrew informed consent before protocol treatment, comprised 478 and 477 pts in the UFT/LV group and SOX group, respectively. The median age was 65.0 years. The ECOG PS was 0 in 94.0%, and the disease stage was IIIA/IIIB/IIIC in 1.3%/50.2%/48.6%. The 3-year DFS rate was 60.6% in the UFT/LV group and 62.7% in the SOX group (HR: 0.90; 95% CI: 0.74-1.09; p = 0.28); the superiority of SOX was not demonstrated. In stage IIIB, the 3-year DFS rate was 69.3% and 68.5% in the UFT/LV group and SOX group, respectively (HR: 1.01; 95% CI: 0.74-1.37; p = 0.95). In Stage IIIC, the 3-year DFS rate was 50.6% and 55.8% in the UFT/LV group and SOX group, respectively (HR: 0.82, 95% CI: 0.63-1.06; p = 0.12). Notably, in the N2b subgroup, the 3-year DFS rate was 46.0% and 54.7% in the UFT/LV group and SOX group, respectively (HR: 0.76, 95% CI: 0.55-1.05; p = 0.10). Conclusions: SOX was not shown to be superior to UFT/LV in pts with high-risk stage III colon cancer. However, the oxaliplatin-based regimen was suggested to be more effective in advanced disease, such as stage IIIC and N2b. Clinical trial information: JapicCTI-101073.

Review of completed and ongoing trials of capecitabine-based adjuvant therapy in patients with early-stage colon cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 495-495
Author(s):  
J. Cassidy ◽  
N. Scotto ◽  
E. Diaz-Rubio
Keyword(s):  
Colon Cancer ◽  
Adjuvant Treatment ◽  
Early Stage ◽  
Single Agent ◽  
Phase Iii ◽  
Stage Iii ◽  
Treatment Regimens ◽  
Phase Iii Trials ◽  
Early Stage Colon Cancer ◽  
Resected Stage

495 Background: Capecitabine is an established alternative to 5-FU in gastrointestinal cancers. In metastatic colorectal cancer, capecitabine is non-inferior to 5-FU and capecitabine + oxaliplatin (XELOX) is non-inferior to FOLFOX4. Capecitabine is also an effective adjuvant treatment for early-stage colon cancer. Here we review the evidence available from completed studies of adjuvant capecitabine and describe ongoing trials in this setting. Methods: The X-ACT trial included 1,987 patients (pts) with resected stage III disease receiving either capecitabine (n=1,004) or bolus 5-FU/LV (n=983). NO16968 included 1,886 pts with resected stage III disease receiving either XELOX (n=944) or 5-FU/LV (n=942). The primary efficacy endpoint of both trials was DFS. Other large phase III trials of capecitabine in high-risk stage II/stage III pts include AVANT (XELOX + bevacizumab vs. FOLFOX4 ± bevacizumab), QUASAR2 (capecitabine vs. capecitabine + bevacizumab), SCOT (capecitabine or 5-FU/LV + oxaliplatin 12w vs. 24w), and a Japanese study of single-agent capecitabine. Results: In X- ACT, capecitabine was at least equivalent to 5-FU/LV in terms of DFS (HR=0.88; 95% CI, 0.77–1.01) and OS (HR=0.86; 95% CI, 0.74–1.01). In a preplanned multivariate analysis, capecitabine led to significantly superior DFS (p=0.02) and OS (p=0.02) vs. bolus 5-FU/LV [Twelves et al. WCGIC 2010]. In NO16968, DFS was significantly superior for XELOX vs. 5-FU/LV (HR=0.80; 95% CI, 0.69–0.93; p=0.0045) [Haller et al. ECCO-ESMO 2009]. There was a trend towards improvement in OS with XELOX (HR=0.87; 95% CI, 0.72–1.05; p=0.1486); follow-up is ongoing. Capecitabine-based therapy had an acceptable safety profile in both trials [Twelves et al. NEJM 2005; Schmoll et al. JCO 2007]. Data have yet to be reported from the AVANT, QUASAR2, SCOT and Japanese trials, although results from these trials in over 15,000 pts are awaited with interest. Conclusions: Adjuvant capecitabine is non-inferior to 5-FU/LV when given as monotherapy and superior to 5-FU/LV when given in combination with oxaliplatin. Capecitabine should be considered as a standard component of adjuvant treatment regimens for pts with stage III disease. [Table: see text]

Smoking status and prognosis in patients with stage III colon cancer: A correlative analysis of NCCTG phase III trial N0147.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3526-3526
Author(s):  
Amanda I. Phipps ◽  
Qian Shi ◽  
Paul J. Limburg ◽  
Garth D. Nelson ◽  
Daniel J. Sargent ◽  
...  
Keyword(s):  
Physical Activity ◽  
Colon Cancer ◽  
Alcohol Consumption ◽  
Braf Mutation ◽  
Smoking Status ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Smoking History ◽  
Mutation Status

3526 Background: Prior observational studies have suggested that smoking is associated with poorer overall survival after colon cancer (CC) diagnosis. Using data from N0147, a phase III randomized adjuvant trial of patients with stage III CC, we assessed the relationship between smoking status and cancer outcomes (disease-free survival (DFS) and time to recurrence (TTR)), accounting for possible heterogeneity by patient and tumor characteristics. Methods: Patients completed a risk factor questionnaire at baseline prior to randomization to FOLFOX or FOLFOX+cetuximab (N=1968). Information was collected on smoking and other lifestyle factors, including alcohol consumption, body mass index (BMI), and physical activity. Multivariate Cox models assessed the association between smoking history and the primary trial outcome of DFS, as well TTR, adjusting for other lifestyle and clinical factors. The median follow-up was 3.5 years. Results: Overall, 52% of patients were former or current smokers. Compared to never smokers, ever smokers experienced significantly shorter DFS [3-year DFS: 70% vs 74%, hazard ratio (HR)=1.21, 95% confidence interval (CI): 1.02-1.42]. This association persisted after adjusting for age, sex, tumor subsite, number of nodes involved, T-stage, mismatch repair deficiency, BRAF mutation status, performance score, physical activity, BMI, and alcohol consumption (HR=1.23, 95% CI: 1.02-1.49). There was significant interaction in this association by BRAF mutation status (p=0.02): smoking was associated with shorter DFS in BRAF wildtype CC patients (HR=1.25, 95% CI: 1.04-1.51) but not in BRAF mutant CC patients (HR=0.72, 95% CI: 0.47-1.10). Patterns of association with smoking, overall and by BRAF status, were identical in analyses of TTR. Conclusions: Overall, smoking was significantly associated with shorter DFS and TTR in CC patients. These adverse relationships were most evident in patients with BRAF wildtype CC.

Sign in / Sign up

Export Citation Format

Share Document