SIDEBAR: Other Colorectal Cancer News from ASCO


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Additional noteworthy gastrointestinal cancer studies presented during oral abstract sessions at the 2012 ASCO Annual Meeting included the following trials in metastatic colorectal cancer.

Perifosine/Capecitabine Fails in Phase III Trial

Adding perifosine, an oral alkylphospholipid inhibitor that targets the Akt pathway, to oral capecitabine (Xeloda) did not significantly improve overall or progression-free survival, vs capecitabine alone, in the X-PECT study.1

The phase III X-PECT trial randomly assigned 468 patients with treatment-refractory metastatic colorectal cancer to the combination or capecitabine alone. Median overall survival was 6.4 months and 6.9 months, respectively, while progression-free survival was 10.9 weeks and 11.4 weeks. However, in a subset of patients with wild-type KRAS who discontinued oxaliplatin because of toxicity, the combination significantly increased progression-free survival from 6.6 weeks to 18.1 weeks (P = .003), reported Johanna C. Bendell, MD, of Sarah Cannon Research Institute, Nashville.

The results contradict those from an earlier randomized phase II trial, in which patients refractory to two prior therapies had a median overall survival of 17.7 months with the combination, vs 7.6 months with capecitabine alone (P = .0052).2 The possibility was raised that the phase II population may not have been less heavily pretreated and were therefore more similar to patients who responded in the phase III trial. An analysis of biomarkers is underway.

Tyrosine Kinase Inhibitors

Two other studies showed benefits for adding tyrosine kinase inhibitors to metastatic colorectal cancer regimens. In the phase III CORRECT trial of 760 highly refractory patients, the oral multikinase inhibitor regorafenib extended overall survival from 5.5 months with placebo to 6.6 months, a 23% reduction in risk (P = .0052).3 Coprincipal investigator Axel Grothey, MD, of the Mayo Clinic, suggested that regorafenib addresses an unmet need for patients with colorectal cancer who exhaust all recommended treatments while still fit enough for chemotherapy.

The phase III GERCOR DREAM trial evaluated the benefit of adding erlotinib (Tarceva) to bevacizumab as maintenance therapy in 700 previously untreated patients with metastatic colorectal cancer who responded to chemotherapy plus bevacizumab.4 Compared to bevacizumab alone, the combination improved median progression-free survival from 4.6 months to 5.8 months (P = .005), though diarrhea and skin toxicity were greater.

Resection of Primary Improves Outcomes

In patients with metastatic colorectal cancer and unresectable metastases, resection of the primary tumor was associated with improved outcomes in a pooled analysis involving individual patient data from four first-line chemotherapy trials.5 Among 810 total patients, a multivariate analysis showed that primary tumor resection (n = 478) was an independent predictor of better overall survival (HR = 0.63; P < .0001) and better progression-free survival (HR = 0.82; P = .0007). The effect of resection was lessened in patients with higher carcinoembryonic antigen levels or a colon (vs rectal) primary tumor. ■

Disclosure: Dr. Bendell reported no potential conflicts of interest. Dr. Grothey has served as an unpaid consultant or advisor for Bayer.

References

1. Bendell JC, Ervin TJ, Senzer NN, et al: Results of the X-PECT study: A phase III randomized double-blind placebo-controlled study of perifosine plus capecitabine versus placebo plus capecitabine in patients with refractory metastatic colorectal cancer. 2012 ASCO Annual Meeting. Abstract LBA3501. Presented June 3, 2012.

2. Bendell JC, Nemunaitis J, Vukelja SJ, et al: Randomized placebo-controlled phase II trial of perifosine plus capecitabine as second- or third-line therapy in patients with metastatic colorectal cancer. J Clin Oncol 29:4394-4400, 2011.

3. Van Cutsem E, Sobrero AF, Siena S, et al: Phase III CORRECT trial of regorafenib in metastatic colorectal cancer. 2012 ASCO Annual Meeting. Abstract 3502. Presented June 3, 2012.

4. Tournigand C, Samson B, Scheithauer W, et al: Bevacizumab with or without erlotinib as maintenance therapy, following induction first-line chemotherapy plus Bev, in patients with metastatic colorectal cancer: Efficacy and safety results of the International GERCOR DREAM phase III trial. 2012 ASCO Annual Meeting. Abstract LBA3500. Presented June 3, 2012.

5. Faron M, Bourredjem A, Pignon J, et al: Impact on survival of primary tumor resection in patients with colorectal cancer and unresectable metastasis: Pooled analysis of individual patients’ data from four randomized trials. 2012 ASCO Annual Meeting. Abstract 3507. Presented June 3, 2012.


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