Æterna Zentaris Partner Keryx Reports a Statistically Significant Benefit in
Survival from Updated Results of a Randomized, Double-Blind,
Placebo-Controlled Phase 2 Study of Perifosine (KRX-0401) in the Treatment of
Advanced Metastatic Colon Cancer
Data Reported at the 2010 ASCO GI Cancers Symposium Demonstrate a Statistically Significant Improvement in Both Time to Tumor Progression and Overall Survival in the Perifosine + Capecitabine Arm Versus Placebo + Capecitabine Arm
QUÉBEC CITY,
Study Design
In this randomized, double-blind, placebo-controlled study conducted at 11 centers across the
The patients in the study were heavily pre-treated, with the arms well-balanced in terms of prior treatment regimens. The median number of prior treatment regimens for all 38 patients was two, with prior treatment regimens for the P-CAP arm versus CAP arm shown in the table below. Notably, all of the patients (with the exception of one CAP arm patient) had been treated with FOLFIRI and/or FOLFOX, almost 80% treated with Avastin(R), and half treated with an EGFR antibody:
------------------------------------------------------------------------- Prior RX P-CAP CAP All Patients (n equals 20) (n equals 18) (n equals 38) ------------------------------------------------------------------------- FOLFIRI 18 (90%) 16 (89%) 34 (89%) ------------------------------------------------------------------------- FOLFOX 15 (75%) 13 (72%) 28 (74%) ------------------------------------------------------------------------- FOLFIRI & FOLFOX 13 (65%) 12 (67%) 25 (66%) ------------------------------------------------------------------------- Avastin(R) 15 (75%) 15 (83%) 30 (79%) ------------------------------------------------------------------------- EGFR Antibody (1) 9 (45%) 10 (56%) 19 (50%) ------------------------------------------------------------------------- 5-FU Refractory Status 14 (70%) 13 (72%) 27 (71%) ------------------------------------------------------------------------- Third Line or greater 18 (90%) 16 (89%) 34 (89%) ------------------------------------------------------------------------- (1) Prior treatment with Erbitux(R) and/or Vectibix(R)
The primary endpoint of this study was to measure Time to Progression (TTP). Overall Response Rate (ORR), defined as Complete Responses (CR) + Partial Responses (PR) by RECIST, and Overall Survival (OS) were measured as secondary endpoints.
Study Results
The P-CAP arm demonstrated a statistically significant advantage for TTP and OS, as well as for the percentage of patients achieving Stable Disease lasting 12 or more weeks (SD) or better, as compared to the CAP arm. The P-CAP arm demonstrated a greater than 60% improvement in OS, a more than doubling of median TTP, and almost a doubling of the percentage of patients achieving SD or better. In addition, the ORR was 20% (including one CR, and durable responses) in the P-CAP arm vs 7% in the CAP arm. The updated efficacy results for all evaluable patients are as follows:
------------------------------------------------------------------------- ORR % greater than or equal to SD CR / PR (min 12 wks) (Duration of n (%) Group n Response) p equals 0.036 ------------------------------------------------------------------------- 20% 1 CR (34 mos - ongoing) P-CAP 20 3 PR (21, 19, 11 mos) 15 (75%) ------------------------------------------------------------------------- 7% CAP 15 1 PR (7 mos) 6 (40%) ------------------------------------------------------------------------- ------------------------------------------------------------------------- Median TTP Median OS* Weeks Months Group p equals 0.0012 p equals 0.0136 ------------------------------------------------------------------------- P-CAP 28 (95% CI (12-48)) 18 (95% CI (10.8-25.7)) ------------------------------------------------------------------------- CAP 11 (95% CI (9-15.9)) 11 (95% CI (5.3-16.9)) ------------------------------------------------------------------------- *Survival is calculated from date of randomization until the date of death from any cause, whether or not additional therapies were received after removal from treatment. NOTE: Kaplan-Meier method used to calculate both TTP and OS. In addition, TTP and Progression Free Survival (PFS) are identical for all patients in the study.
Of notable interest, and for the first time presented, were data showing a highly statistically significant benefit in median OS (more than doubling) and TTP for the subset of patients who were refractory to a 5-FU (Fluorouracil) chemotherapy-based treatment regimen. 5-FU is a core component of the standard of care FOLFIRI and FOLFOX regimens, and capecitabine is a 5-FU pro-drug. These results are shown below:
------------------------------------------------------------------------- greater than or equal to SD (min 12 wks) 5-FU Ref n (%) Group n (%) p equals 0.066 ------------------------------------------------------------------------- P-CAP 14 (70%) 1 PR / 8 SD (64%) ------------------------------------------------------------------------- CAP 11 (73%) 0 PR / 3 SD (27%) ------------------------------------------------------------------------- ------------------------------------------------------------------------- Median TTP Median OS Weeks Months Group p equals 0.0004 p equals 0.0088 ------------------------------------------------------------------------- P-CAP 18 (95% CI (12-36)) 15.3 (95% CI (8.4-26)) ------------------------------------------------------------------------- CAP 10 (95% CI (6.6-11)) 6.8 (95% CI (4.8-11.7)) -------------------------------------------------------------------------
All 38 patients were evaluable for safety. The P-CAP combination was well-tolerated with Grade 3 and Grade 4 adverse events of (greater than) 10% incidence for P-CAP arm versus CAP arm as follows: anemia (15% vs. 0%), fatigue (0% vs. 11%), abdominal pain (5% vs. 11%) and hand-foot syndrome (30% vs. 0%). Of note, incidence of Grade 1 and Grade 2 hand-foot syndrome was similar in both the P-CAP and CAP arms (25% vs. 22%, respectively). Hand-foot syndrome is a reported adverse event with capecitabine monotherapy. Patients who remained on treatment longer in the Phase 2 study had a greater chance to develop hand-foot syndrome as illustrated by a median time to onset of Grade 3 and Grade 4 hand-foot syndrome in the P-CAP arm of 19 weeks.
Commenting on the data,
Juergen Engel, Ph.D., President and CEO at Æterna Zentaris stated, "This is a very positive development to begin the Year 2010. We now have a lot of options to create value for our shareholders with our late-stage compounds in oncology, perifosine and AEZS-108, as well as in endocrinology with AEZS-130, thanks to the successful collaboration with our partner Keryx and the continuous interest of dedicated investigators. We now look forward to the further development of perifosine."
A copy of the abstract is available upon request.
About Colorectal Cancer
According to the American Cancer Society, colorectal cancer is the third most common form of cancer diagnosed in the
About Perifosine (KRX-0401)
Perifosine is a novel oral anticancer agent that modulates several key signal transduction pathways, including Akt, MAPK, and JNK that have been shown to be critical for the survival of cancer cells. Perifosine has demonstrated both safety and clinical efficacy in several tumor types, both as a single agent and in combination with novel therapies. Perifosine is currently in a Phase 3 trial, under Special Protocol Assessment (SPA), in multiple myeloma for which it has received Orphan Drug and Fast Track designations from the FDA in this indication. Perifosine is also in Phase 2 clinical trials for several other tumor types.
About Æterna Zentaris Inc.
Æterna Zentaris Inc. is a late-stage drug development company specialized in oncology and endocrinology. News releases and additional information are available at www.aezsinc.com.
Forward-Looking Statements
This press release contains forward-looking statements made pursuant to the safe harbor provisions of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements involve known and unknown risks and uncertainties, which could cause the Company's actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of the Company to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. Investors should consult the Company's quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned not to rely on these forward-looking statements. The Company does not undertake to update these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments except if we are required by a governmental authority or applicable law.
For further information: For further information: Investor Relations: Dennis Turpin, SVP and CFO, (418) 652-8525, ext. 242, [email protected]; Media Relations: Paul Burroughs, Director of Communications, (418) 652-8525, ext. 406, [email protected]
Share this article