Faculty Opinions recommendation of Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment for patients with advanced colorectal cancer: a double-blind, randomized phase III study (HORIZON III).

PurposeThis phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI).Patients and MethodsA total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity.ResultsMedian PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of ≥ grade 3 hypertension than mIFL+Bev.ConclusionFOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.

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Capecitabine plus irinotecan versus 5-FU/FA/irinotecan +/− celecoxib in first line treatment of metastatic colorectal cancer. Safety results of the prospective multicenter EORTC phase III study 40015

Journal of Clinical Oncology ◽

10.1200/jco.2005.23.16_suppl.3525 ◽

2005 ◽

Vol 23 (16_suppl) ◽

pp. 3525-3525 ◽

Cited By ~ 12

Author(s):

C.-H. Kohne ◽

J. de Greve ◽

C. Bokemeyer ◽

I. Lang ◽

P. Vergauwe ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Phase Iii ◽

Line Treatment ◽

First Line ◽

Phase Iii Study ◽

First Line Treatment

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Double-blind, randomized, parallel group, phase III study to demonstrate equivalent efficacy and comparable safety of CT-P6 and trastuzumab, both in combination with paclitaxel, in patients with metastatic breast cancer (MBC) as first-line treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.629 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 629-629 ◽

Cited By ~ 12

Author(s):

Young-Hyuck Im ◽

Petro Odarchenko ◽

Daniela Grecea ◽

Dmitry Komov ◽

Chernobay Valentynovych Anatoliy ◽

...

Keyword(s):

Median Time ◽

Data Monitoring Committee ◽

Metastatic Breast ◽

Pooled Analysis ◽

Phase Iii ◽

Line Treatment ◽

First Line ◽

Double Blind ◽

Phase Iii Study ◽

First Line Treatment

629 Background: CT-P6(C) is an anti-HER2 MoAb, a biosimilar to trastuzumab (T). This trial is a global phase III study to compare C with T, both in combination with paclitaxel (P) as first-line treatment in women with HER2+ MBC. Methods: 475 patients with centrally confirmed HER2+ MBC were randomized to receive either C+P (n=244) or T+P (n=231). Patients had to have a baseline LVEF ≥50% and no history of serious cardiac disease. Study medication was as follows: C or T 8 mg/kg i.v. (day 1), followed by 3-weekly C or T 6 mg/kg. P (175 mg/m23-weekly) was co-administered. The primary endpoint was overall response rate (ORR) as determined by independent review. Pooled analysis with data from phase I/IIb (NCT01084863) and III studies (NCT01084876) was predefined and endorsed by the EMA. Patient safety was monitored throughout the study by an independent data monitoring committee. Treatment was continued until disease progression, death or patient’s withdrawal. Results: In the pooled ITT population, ORR was 57% for C+P and 62% for T+P (difference: 5%; 95% CI: -0.14, 0.04) during the first 8 cycles of treatment. The limits of the 95% CIs for the difference in the proportions of responders were contained within the pre-defined range [-0.15, 0.15] required for equivalence. Median time to progression and median time to response were 11.07 vs. 12.52 months (P =0.10), and 1.38 vs. 1.38 months (P =0.37) for C+P and T+P, respectively. Frequency of treatment-related AEs is shown in the Table. Conclusions: Equivalence of C and T was observed for ORR in patients with HER2+ MBC in combination with P as first-line therapy. Secondary efficacy endpoints also supported the comparability between C and T. C was well tolerated with a safety profile comparable to that of T. Clinical trial information: NCT01084876. [Table: see text]

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