Complete Study Results Comparing CTI's OPAXIO(TM) With Gemcitabine Or Vinorelbine In Performance Status (PS 2) NSCLC Patients

Main Category: Lung Cancer
Article Date: 07 Jul 2008 - 2:00 PDT

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Cell Therapeutics, Inc. (CTI) announced the publication of results from its randomized phase III trial comparing OPAXIO(TM) (paclitaxel poliglumex, CT-2103) with gemcitabine or vinorelbine for the treatment of PS 2 (performance status 2) patients with previously untreated non-small cell lung cancer (NSCLC) in the Journal of Thoracic Oncology (Volume 3, Number 7, July 2008). Results showed that overall survival was similar between the two arms (hazard ratio of 0.95; OPAXIO to control).

Patients treated with OPAXIO required less supportive care including fewer red blood cell transfusions, hematopoietic growth factors, and opioid analgesics than those patients receiving either gemcitabine or vinorelbine. There were relatively few non-hematopoietic grade 3 or 4 toxicities in either arm. Additionally, patients receiving OPAXIO required fewer clinic visits due to its administration schedule, once every three weeks, and short infusion time, compared to patients receiving either gemcitabine or vinorelbine.

The objective of the study, known as STELLAR 4, was to determine if OPAXIO would improve overall survival when compared with the standard single-agent treatments of gemcitabine or vinorelbine in PS 2 patients with advanced NSCLC who had not previously received chemotherapy. The trial did not meet the primary endpoint. Secondary objectives of the study included measuring the efficacy and safety of the treatments. OPAXIO did demonstrate similar overall survival and a reduction in the supportive care required by patients.

A total of 190 patients with advanced NSCLC were randomized to the comparator arm; 191 were randomized to the OPAXIO arm with a dosage of 175 mg/m^2, and 96 were randomized to the OPAXIO arm at a dosage of 235 mg/m^2. The OPAXIO dose was reduced to 175 mg/m^2 after 96 patients had been treated, because the Data Monitoring Committee noted an increase in deaths associated with neutropenia in patients who had received the 235 mg/m^2 dosage. The following data refers to those patients treated at the OPAXIO dose of 175 mg/m^2. The median number of cycles administered was 4, with a median of 3.5 in the control arm.

A total of 754 cycles of OPAXIO were administered, and 652 cycles were administered in the comparator arm. More patients in the OPAXIO arm received 6 cycles of treatment (38 percent versus 23 percent; p = 0.002). Progressive disease was the most common reason for not completing 6 cycles (55 percent in the OPAXIO arm and 59 percent in the comparator arm). Fewer OPAXIO patients (12 percent) discontinued treatment as a result of adverse events, compared to 17 percent of patients in the control arm. Survival, time to progression (TTP), and response rates were similar in both arms. Median overall survival was 7.3 months in the OPAXIO arm and 6.6 months in the control arm. The estimated 1-year survival rate was the same in both arms (26 percent), and the approximate 2-year survival rate was numerically higher in the OPAXIO arm (15 percent) than the comparator arm (10 percent). There was a lower requirement for red blood cell transfusions (p = 0.001), erythropoietin use (p = 0.014), myeloid growth factors (p = 0.032), and new narcotic analgesics (p = 0.034) in the OPAXIO arm when compared to the control arm. No significant differences were evident in quality of life based on FACT-LCS evaluations between the two arms. OPAXIO patients experienced fewer hematologic (p <0.001) and gastrointestinal (p = 0.004) adverse events. Neuropathy occurred more frequently in the OPAXIO arm compared with the control arm (30 percent versus 5 percent, (p <0.001)), and grade 3 neuropathy occurred in 4 percent of the OPAXIO patients, with no occurrences of grade 4 neuropathy. There was a lower incidence of alopecia in the OPAXIO arm (2 percent versus 5 percent respectively, p = 0.085), as well as fatigue (16 percent versus 25 percent, p= 0.055), asthenia (11 percent versus 16 percent, p = 0.169), and weight loss (7 percent versus 12 percent, p = 0.121).

Details of the Study

The phase III trial, reported by Mary E. R. O'Brien, M.D., F.R.C.P., et al, of the Royal Marsden Hospital and the Kent Cancer Centre in Surrey, UK, was a randomized, multi-center trial. The trial was conducted at 83 centers in ten countries, and randomized on a 1:1 ratio to evaluate the efficacy and safety of this regimen in patients with chemotherapy-naïve NSCLC. Patients with advanced stage IIIb/IV NSCLC and PS 2 were treated with OPAXIO on day 1 of a 21-day cycle, while patients receiving gemcitabine were treated on days 1, 8, and 15 of each 28-day cycle. Vinorelbine was administered on days 1, 8, and 15 of each 21-day cycle. Patients received up to six cycles of treatment, and were not treated until significant toxicities were under control (less than or equal to grade 1). The primary objective was effect on survival, and secondary objectives were determining the efficacy and safety of the treatments.

About OPAXIO(TM)

OPAXIO(TM) (paclitaxel poliglumex, CT-2103), which was previously branded as XYOTAX(TM), is an investigational, biologically enhanced, chemotherapeutic that links paclitaxel, the active ingredient in Taxol(R), to a biodegradable polyglutamate polymer, which results in a new chemical entity. When bound to the polymer, paclitaxel is rendered inactive, potentially sparing normal tissue's exposure to high levels of the active drug and its associated toxicities. Blood vessels in tumor tissue, unlike blood vessels in normal tissue, are porous to molecules like polyglutamate. Based on preclinical studies, it appears that OPAXIO is preferentially distributed to tumors due to their leaky blood vessels and trapped in the tumor bed allowing significantly more of the dose of chemotherapy to localize in the tumor than with standard paclitaxel. Once inside the tumor cell, enzymes metabolize the protein polymer, releasing the paclitaxel chemotherapy. Preclinical and clinical studies support that OPAXIO metabolism by lung cancer cells may be influenced by estrogen, which could lead to enhanced release of paclitaxel and efficacy in women with lung cancer compared to standard therapies. This is being studied in an ongoing phase III trial.

About Cell Therapeutics, Inc.

Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit http://www.celltherapeutics.com.

This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of OPAXIO include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with OPAXIO in particular including, without limitation, risks that the OPAXIO MAA may not result in a marketing approval in Europe, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling OPAXIO in the various countries in Europe if OPAXIO is approved for marketing in Europe, and the risk factors listed or described from time to time in the Company's filings with the Securities and Exchange Commission including, without limitation, the Company's most recent filings on Forms 10-K, 8-K, and 10-Q. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.

Cell Therapeutics, Inc.