ASCO NEWS: CLINICAL TRIALS UPDATE 6.22.11
Clinical trials for newly diagnosed patients
Interim analysis from ICON7, which used avastin in the maintenance setting following addition to carboplatin and taxol in newly diagnosed patients, confirmed the significant advantage in progression free survival (PFS) previously shown (19.8 vs. 17.4 months) and a trend for increased overall survival (OS) in the total patient population (HR of 0.85). New analysis showed that a sub-group of patients with poor prognosis (i.e., stage III suboptimal debulking status or stage IV) had greater benefit from avastin maintenance therapy (OS: 36.6 mos vs. 28 mos.; HR of 0.64). Final analysis is expected in 2013.
Clinical trials for treatment of recurrent disease
In the OCEANS phase III trial, recurrent platinum-sensitive patients at first relapse were given carboplatin/gemzar plus avastin with continuation avastin. There was a significant PFS advantage for patients in the avastin arm (ie., 12.4 vs. 8.4 mos.) and the preliminary analysis of still-not-mature data showed an OS of 35.5 vs. 29.9 mos. in favor of the avastin arm.
Results from a number of phase II trials were reported. Comparison of responses of the different agents tested is difficult at this stage of clinical development because the number of patients treated is not large and the characteristics of the patients in each of the trials can be quite different (e.g., number of prior treatments, length of time following platinum-based therapy, etc). However, promising early results were reported for several drugs, including olaparib and iniparib that target the DNA repair enzyme, poly-ADP-ribose polymerase (PARP), a new angiogenesis inhibitor, and drugs that are comprised of cytotoxic chemotherapies linked to either a metabolite (EC145) to target to the tumor or a macromolecule (NKTR-102) to stabilize it in the blood stream.
Olaparib was given in a phase II trial as maintenance therapy to patients who had maintained partial or complete responses to platinum-based therapy and had received at least two prior platinum-based therapies. Olaparib showed significant disease control with PFS 8.4 vs. 4.8 mos. in the placebo group.
Iniparib was given in two phase II trials in combination with gemcitabine and carboplatin. In platinum platinum-sensitive patients, iniparib had a 70% partial response (PR) and 30% stable disease (SD) with PFS of 9.5 mos. In platinum-resistant patients, iniparib showed 25% PR, 50% SD with PFS 6.4 mos.
A new angiogenesis inhibitor, Aflibercept, is called a VEGF Trap and is a VEGF receptor fusion protein that acts as a decoy to bind VEGF. It was given in combination with docetaxel in the recurrent setting and showed responses in 77% of platinum-sensitive and 45% platinum-resistant patients. PFS was 6.2 mos. and OS 24.3 mos.
EC145 is folate-vinca alkaloid conjugate that is taken into the tumor by the folate receptor, which is highly expressed in 80% of ovarian cancers. EC145 thereby delivers a cytotoxic drug to the cancer cell that expresses this receptor. Tumors that have the folate receptor are imaged by scanning for technetium-labeled folate (EC20). EC145 was given to platinum-resistant patients in combination with Doxil and PFS of 21.7 wks vs. 11.7 wks were observed in the unselected patient population; 24 wks vs. 6.1 wks in the EC20 positive population.
NKTR-102 is a macromolecular conjugate of the topoisomerse 1 inhibitor irinotecan that stabilizes the drug to allow a more steady and continuous availability to the tumor than occurs with the free drug. 20% of the platinum-resistant and refractory patients who had already progressed on Doxil responded with a PFS of 5.4 mos. and OS 13.9 mos.
