End Points for Colon Cancer Adjuvant Trials: Observations and Recommendations Based on Individual Patient Data From 20,898 Patients Enrolled Onto 18 Randomized Trials From the ACCENT Group

Sargent, Daniel J.; Patiyil, Smitha; Yothers, Greg; Haller, Daniel G.; Gray, Richard; Benedetti, Jacqueline; Buyse, Marc; Labianca, Roberto; Seitz, Jean François; O’Callaghan, Christopher J.; Francini, Guido; Grothey, Axel; O’Connell, Michael J.; Catalano, Paul J.; Kerr, David; Green, Erin; Wieand, Harry S.; Goldberg, Richard M.; Gramont, Aimery de

doi:10.1200/jco.2006.10.4323

Cited by 217 publications

(149 citation statements)

References 20 publications

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“…The correlation between treatment effects on PFS and OS in each trial was only moderate (trial-level decision coefficient R 2 adjusted for estimation errors was 0.61), which is the same strength of relationship seen in the literature-based analysis [14]. Correlations between PFS and PS were lower for AGC than for those in patients with advanced colorectal cancer [10] or for those seen in studies of adjuvant treatment for colorectal cancer or gastric cancer [20,21]. These results suggest that PFS is not a good surrogate for OS in patients undergoing firstline chemotherapy for AGC.…”

Section: Discussionsupporting

confidence: 54%

Correlation between overall survival and other endpoints in clinical trials of second-line chemotherapy for patients with advanced gastric cancer

et al. 2013

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Background The correlation between progression-free survival (PFS) or time to progression (TTP) and overall survival (OS) has been evaluated in patients with advanced gastric cancer (AGC) who received first-line chemotherapy. No corresponding analysis has been done in patients who have undergone second-line chemotherapy. Methods We evaluated the correlation between PFS, TTP, objective response rate (ORR), disease control rate (DCR), and OS in patients with AGC who underwent second-line chemotherapy. Correlations were evaluated by Spearman rank correlation coefficient (q). Results Sixty-four trials, including 10 randomized studies, were selected for analysis. Median PFS/TTP moderately correlated with OS (q = 0.56). The correlation tended to be stronger in non-Asian trials (q = 0.74) than in Asian trials (q = 0.37). ORR and DCR did not strongly correlate with OS (q = 0.38 for ORR; q = 0.54 for DCR). The hazard ratio of PFS and OS in each of the arms of the 10 randomized studies also showed a low correlation (q = 0.36). Conclusions PFS/TTP, ORR, and DCR did not correlate sufficiently with OS to be used as surrogate endpoints in patients with AGC who have undergone second-line chemotherapy. Further research is needed based on individual patient data from ongoing randomized trials.

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Section: Discussionsupporting

confidence: 54%

Correlation between overall survival and other endpoints in clinical trials of second-line chemotherapy for patients with advanced gastric cancer

et al. 2013

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“…Moreover, we have a relatively long follow up period with the median followup time in this study being 4.31 years. Notably, 3-year DFS is a strong predictor of OS for 5FU-containing combination chemotherapy (Sargent et al, 2007) and it is agreed by various regulatory authorities to be adopted as the candidate for primary end point for adjuvant cancer trials. Therefore, we believe our data are mature enough to shed light in this important topic.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Tolerability of Adjuvant Oral Capecitabine plus Intravenous Oxaliplatin (XELOX) in Asian Patients with Colorectal Cancer: 4-Year Analysis

Chiu

Tang²,

Leung³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Although FOLFOX (infusional fluorouracil/leucovorin plus oxaliplatin) is established as a standard chemotherapeutic regimen, the long term efficacy of adjuvant XELOX (oral capecitabine plus intravenous oxaliplatin) in Asian colorectal cancer (CRC) patients remains anecdotal. Moreover, uncertainties persist as to whether pharmacogenetic differences in Asian populations preclude equally tolerable and effective administration of these drugs. Method: One hundred consecutive patients with resected colorectal cancer received adjuvant XELOX (oxaliplatin 130 mg/m 2 on day 1 plus capecitabine 900 mg/m 2 twice daily on day 1 to 14 every 3 weeks for 8 cycles) at Queen Mary Hospital, Hong Kong. Endpoints monitored during follow-up were disease-free survival (DFS) and disease recurrence, overall survival (OS) and adverse events (AEs). Results: The median patient age was 56 years, 56% were diagnosed with rectal cancer and 44% with colonic cancer. After a median follow-up of 4.3 years (95% confidence interval, 3.2-4.7), 24 recurrences were confirmed including 13 patients who died due to progressive disease. Four-year DFS was 81% in colon cancer patients and 67% in rectal cancer patients (p=0.06 by log-rank test). For the cohort as a whole, OS was 90% at 3 years and 84% at 5 years. Treatment-related AEs led to early withdrawal in four patients. The commonest non-hematological AEs were neuropathy (91%), hand-foot syndrome (49%) and diarrhea (46%), while the commonest grade 3/4 AEs were neutropenia (11%) and diarrhea (10%). Conclusion: These results confirm the favourable long term survival benefit with good tolerability in using adjuvant XELOX in treating East Asian colorectal cancer patients.

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“…As with the similar GASTRIC and ACCENT databases in gastric and adjuvant colorectal cancer [11,12], the patientlevel approach adopted in the ARCAD database provides a more informative and statistically robust basis for research than could be achieved through meta-analyses based on published literature or summary statistics. Compared with these methodologies, the individual-patient approach reduces publication and reporting bias, gives access to the most recent data, permits data checking, and, crucially, affords greater scope for novel analyses [13,14].…”

Section: Gastrointestinal Cancermentioning

confidence: 99%

The ARCAD Clinical Trials Program: An Update and Invitation

Sargent

Buyse

Matheson³

et al. 2012

The Oncologist

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It is widely accepted that traditional models of clinical investigation are becoming unsustainable in oncology and that trials must become more efficient in matching effective treatments to the patients most likely to benefit. In 2008, gastrointestinal oncologists from many countries began a collaboration to improve the design and conduct of clinical trials in their field, through the auspices of a French/U.S. charitable foundation, ARCAD. Whether this model of academic collaboration will be judged a success will depend on the quality of its scientific output during the next few years and whether this output, alongside that of other scientists, groups, and institutions, ultimately leads to more efficient trials and improved treatment options for patients.

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End Points for Colon Cancer Adjuvant Trials: Observations and Recommendations Based on Individual Patient Data From 20,898 Patients Enrolled Onto 18 Randomized Trials From the ACCENT Group

Cited by 217 publications

References 20 publications

Correlation between overall survival and other endpoints in clinical trials of second-line chemotherapy for patients with advanced gastric cancer

Correlation between overall survival and other endpoints in clinical trials of second-line chemotherapy for patients with advanced gastric cancer

Efficacy and Tolerability of Adjuvant Oral Capecitabine plus Intravenous Oxaliplatin (XELOX) in Asian Patients with Colorectal Cancer: 4-Year Analysis

The ARCAD Clinical Trials Program: An Update and Invitation

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