XYOTAX(TM) Significantly Prolongs Survival in Poor Performance Status (PS2) Non-small Cell Lung Cancer Patients Compared to Standard Treatment With Vinorelbine
Sunday May 15, 7:00 am ET
Phase III Trials Demonstrate XYOTAX Offers Less Toxic, More Convenient Treatment Option over Current Therapies for PS2 Lung Cancer
ORLANDO, Fla., May 15 /PRNewswire/ -- In an oral session and at a meeting of the STELLAR trial investigators at the 2005 Annual Meeting of the American Society of Clinical Oncology (ASCO), Corey J. Langer, M.D., of Fox Chase Cancer Center, reported preliminary data from two phase III studies of XYOTAX for the first-line treatment of non-small cell lung cancer (NSCLC) patients with poor performance status 2 (PS2). Both studies were designed to determine if XYOTAX could improve survival while reducing serious side effects when compared to standard single agents, gemcitabine or vinorelbine (STELLAR 4) or when used with a second chemotherapeutic agent, carboplatin (STELLAR 3).
In the study known as STELLAR 4, patients who received single-agent XYOTAX experienced a 40 percent improvement in overall survival which was statistically significant when compared to patients who received one of the control agents, vinorelbine. Vinorelbine is the only single agent approved in the United States for treating first-line lung cancer. On study deaths were also significantly reduced among XYOTAX recipients compared to patients receiving gemcitabine or vinorelbine. In addition, XYOTAX patients had a significant reduction in nausea/vomiting and in severe (grade 3/4) side effects, including infections, pneumonia, and neutropenia, when compared to patients treated with vinorelbine. While numbness and tingling in hands and feet was higher among patients receiving XYOTAX, the occurrence of Grade 3 neuropathy was low (4 percent). Significantly more XYOTAX patients were able to complete full six doses of therapy than patients receiving vinorelbine. XYOTAX patients had a higher incidence of poor prognostic risk factors, including multiple sites of metastatic disease, advanced stage IV disease, and multiple co-morbid conditions when compared to the vinorelbine control arm. There were no major differences in post-study therapies between the treatment arms.
In the study known as STELLAR 3, the combination of XYOTAX/carboplatin yielded similar rates of overall survival in the first-line treatment of PS2 patients with NSCLC as the current standard paclitaxel/carboplatin; 31 percent of patients on either treatment arm survived one year. With the exception of low platelets, a side effect that was higher among XYOTAX recipients, XYOTAX was better tolerated, with a significant reduction in joint pains, cardiac events and hair loss while providing a more convenient infusion (48 minutes vs. 228 minutes) than the current standard paclitaxel/carboplatin therapy. Mild nausea and vomiting were significantly higher among XYOTAX recipients, possibly due to the lack of routine anti-emetic pre-medications that were standard in the control arm. Severe (grade 3-4) nausea and vomiting was comparable between the two arms.
"These are the first dedicated phase III trials in treating PS2 patients with lung cancer and they demonstrate that for platinum based doublet therapy, XYOTAX arguably provides an easier to administer, better tolerated, more convenient first-line treatment for PS2 patients over paclitaxel," stated Langer. "As a single agent, XYOTAX offers this underserved patient population a better tolerated, less toxic treatment option than chemotherapeutic agents currently available for these frail patients. Compared to vinorelbine, XYOTAX also has been shown to be more effective."
"We believe the survival advantage seen with XYOTAX over the approved agent vinorelbine, the overall significant reduction in on-study deaths, along with the significant reduction in clinically important disease symptoms and toxicities associated with standard agents (gemcitabine, vinorelbine, paclitaxel and or docetaxel) provides a route for potential registration as a single agent in the first-line treatment setting for PS2 non-small cell lung cancer patients. This is a population of patients that have an unmet medical need for less toxic and effective therapy," noted Jack Singer, M.D., Chief Medical Officer.
Updated STELLAR 4 Trial Results
The STELLAR 4 trial is a randomized pivotal trial of XYOTAX versus standard single-agent therapy with either gemcitabine or vinorelbine for the first-line treatment of poor performance status (PS2) patients with NSCLC. CTI previously reported that XYOTAX resulted in a non-significant increase in median survival when compared to the control patients who received either gemcitabine or vinorelbine (7.3 months vs. 6.6 months, p=0.75). When each drug in the control arm of the study was analyzed individually on an intent to treat basis, XYOTAX resulted in a significant prolongation of survival compared to patients randomized to receive treatment with vinorelbine (n=32, log rank p=0.012, HR 0.60). Twenty-six percent of XYOTAX recipients were alive at one year compared to seven percent of patients who received vinorelbine. At two years, 15 percent of XYOTAX patients were alive compared to none of the vinorelbine recipients and 12 percent of gemcitabine recipients. Patients treated with XYOTAX had a significant reduction in on-study deaths compared to patients treated with either gemcitabine or vinorelbine (14 percent vs. 23 percent, p=0.023). Consistent with previously reported safety results for STELLAR 4, patients receiving treatment with XYOTAX had a significant reduction in a number of potentially life threatening side effects (grade 3/4) compared to control patients. The incidence of serious (grade 3) neuropathy was higher in the XYOTAX patients (4 percent) but neither control drug is typically associated with neuropathy as a common side effect. Complete results of this trial including lung cancer symptom scores will be presented at the International Association for the Study of Lung Cancer (IASLC) meeting in July.
STELLAR 3 Trial Results
STELLAR 3, is a phase III clinical trial comparing the effect of standard paclitaxel/carboplatin to XYOTAX/carboplatin in the first-line treatment of PS2 lung cancer. The one-year survival rate was 31 percent for both arms and two-year survival rate was 13 percent for XYOTAX compared to 11 percent for paclitaxel. As specified in the protocol, the outcome was analyzed by regions, i.e. U.S. vs. Canada plus Western Europe vs. other sites (predominantly in Eastern Europe). Patients in Eastern Europe were approximately 10 years younger, had less advanced lung cancer, a lower incidence of other medical conditions, and fewer had received prior radiation. These differences may account for the improved survival in this study when compared to previously reported similar studies in PS2 patients. The paclitaxel arm in the U.S. region of the study mirrored recent published experience where 19 percent of patients survived one year compared to 28 percent for XYOTAX recipients (p=0.26). Compared to the control patients, XYOTAX/carboplatin infusion time was significantly shorter than that required for paclitaxel /carboplatin (48 minutes vs. 224 minutes, p<0.006), did not require routine pre-medications, resulted in significantly less hair loss (14 percent vs. 42 percent, p<0.001), musculoskeletal (14 percent vs. 27 percent, p=0.002), and cardiac side effects (0 percent vs. 3 percent, p=0.01). The overall incidence of neuropathy was lower on the XYOTAX arm (47 percent vs. 56 percent, p=0.09), although grade 3 was numerically higher. There was a significant delay in the onset of neuropathy between the XYOTAX and paclitaxel arms (89 days vs. 54 days, p<0.001). With the exception of more grade 3/4 thrombocytopenia on the XYOTAX arm, there were no significant differences in other grade 3/4 toxicities including severe neuropathy, nausea, vomiting, neutropenia, infection or febrile neutropenia between the two treatment arms. Additional results will be presented at the IASLC meeting in July.
About XYOTAX(TM)
XYOTAX (paclitaxel poliglumex) is a pharmaceutical that links paclitaxel, the active ingredient in Taxol®, to a biodegradable polyglutamate polymer. This polymer technology results in a new chemical entity, designed to selectively deliver higher and potentially more effective levels of active chemotherapeutics to tumors. Blood vessels in tumor tissue, unlike blood vessels in normal tissue, are porous to molecules like polyglutamate. Based on preclinical studies, it appears that XYOTAX is preferentially trapped in the tumor blood vessels allowing significantly more of the dose of chemotherapy to localize in the tumor. Because more of the chemotherapy is targeted to the tumor and the levels of chemotherapy delivered to normal tissue are reduced, XYOTAX may be potentially more effective and have less severe side effects than currently available chemotherapeutics.
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 cticseattle.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 XYOTAX include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with XYOTAX in particular including, without limitation, the potential failure of XYOTAX to prove safe and effective or to be approved for use in non-small cell lung and ovarian cancers, risks that the results of any single STELLAR trial or the body of data from all 3 STELLAR trials will not be sufficient for FDA to approve XYOTAX for the treatment of lung cancer, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling XYOTAX, 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. CTI is under no obligation to (and expressly disclaims any such obligation to) update or alter its forward-looking statements whether as a result of new information, future events, or otherwise. |
