AstraZeneca Eliminates Advanced Colorectal Cancer Claim For Recentin

AstraZeneca will no longer file marketing applications in the U.S. and Europe this fall for Recentin (cediranib) in first-line metastatic colorectal cancer after the oral VEGF inhibitor failed to show an overall survival benefit in the Phase III HORIZON II study, the company announced May 28.

Though there are no further plans to develop cediranib in mCRC, the biopharma isn't ready to throw the towel in on the compound altogether.

The next inflection point for cediranib comes with the forthcoming results of the Phase III REGAL study testing the drug in recurrent glioblastoma. The three-armed study, which has hit its recruitment goal of around 300 patients and is ongoing, tests cediranib as monotherapy and in combination with lomustine chemotherapy against chemotherapy alone. The primary endpoint is progression free survival, tracked via MRI. Secondary endpoints include overall survival and response rate at six months, as well as steroid-sparing effects.

Depending on how cediranib fares in that program, the company will go ahead with other tumor types, it said. AstraZeneca has U.S. and European filings for glioblastoma penciled in for the fourth quarter of this year, which had been the projection for mCRC as well.

Final results from a 31-patient Phase II study sponsored by the National Cancer Institute were published May 10. The study met the primary endpoint, with just over a quarter of the patients alive and progression-free at six months. Median PFS was 117 days, and median overall survival was 227 days.

In addition, cediranib demonstrated a steroid-sparing effect. Of 15 patients on corticosteroids at enrollment, 10 were able to reduce their dose, and the other five were able to discontinue altogether. The most common adverse events were hypertension, fatigue and diarrhea. Fifteen patients required at least one dose reduction and 15 required an interruption, but the interruptions were not associated with mortality or disease progression.

The HORIZON CRC Program Was Never Easy

The Phase II brain cancer results are more promising than early CRC studies. Data from the HORIZON program were not ready for presentation at the American Society of Clinical Oncology meeting in June, but they will be submitted to a future medical congress, the company said.

HORIZON II tested cediranib in combination with chemotherapy, either FOLFOX (folinic acid, 5FU and oxaliplatin) chemotherapy or XELOX (capecitabine and oxaliplatin). The primary endpoints were PFS, which it met, and overall survival, for which it failed to show improvement.

In the Phase II/III HORIZON III study, which tested cediranib with FOLFOX against bevacizumab (Roche/Genentech's Avastin ) plus FOLFOX, cediranib failed to show either superiority or non-inferiority in PFS. AstraZeneca reported those results in March.

Data from the HORIZON I study were inconclusive as to whether the compound should move into Phase III, but together with the Phase II portion of HORIZON III, the data were thought to justify advancement.

Cediranib had a Phase II setback in non-small cell lung cancer in 2008, when a study of the compound in combination with paclitaxel and carboplatin against chemotherapy alone showed a toxicity signal (¹ (Also see "AstraZeneca Recentin To Start Phase III For Colorectal Cancer, But Not NSCLC" - Pink Sheet, 1 Mar, 2008.)).

But while the company did not progress cediranib into Phase III for NSCLC at the time, AstraZeneca confirmed the drug is being carried in the pipeline for that indication with filings targeted for the U.S. and Europe in 2013. The company is set to update its pipeline at the time of its half-year earnings report, scheduled for July 29.

- Shirley Haley (² [email protected])