Surgery News - January 2008 - (Page 6) THORACIC SURGERY NEWS • J A N U A RY 2 0 0 8 FDA Advisers Back Approval of Thoratec LVAD B Y A L I C I A A U LT Else vier Global Medical Ne ws G A I T H E R S B U R G, M D. — A Food and Drug Administration advisory committee has recommended approval of a next-generation left ventricular assist device system, the Thoratec HeartMate II, even though it failed to meet the agency’s performance goal. The Circulatory System Devices Panel unanimously voted to approve the device, with conditions, with a majority of committee members saying that they had reasonable assurance of the HeartMate’s safety and efficacy. If approved, the HeartMate II could be used both in and out of the hospital as a bridge-to-transplant in patients at risk of imminent death from nonreversible left ventricular failure. Among the conditions of approval: The committee directed Thoratec to conduct a postapproval study, with an emphasis on acquiring more data on how HeartMate II works in smaller patients (with a body surface area of less than 1.3 m2), and on standardizing data collection on perioperative management of hemorrhagic and thrombotic events. As part of the study, there should be a concurrent comparator arm, said the panel. Committee members also urged the company to clarify labeling to separately describe data from two other nonpivotal studies Thoratec submitted with the application. One was in patients with a body surface area of less than 1.2 m2 and one was a continuing access protocol study. The committee asked Thoratec to state on the label that patients who cannot be anticoagulated should not receive the device. The postapproval study will be conducted through the Interagency Registry of Mechanical Assisted Circulatory Support (INTERMACS), a joint effort of the National Heart, Lung, and Blood Institute, the FDA, the Centers for Medicare and Medicaid Services, and individual clinicians, scientists, and industry representatives in conjunction with the University of Alabama, Birmingham, and the United Network for Organ Sharing. “I think the sentiment here is that [HeartMate] has met reasonable assurance of effectiveness despite the fact that the data did not meet the prespecified performance goal,” said panel chairman Dr. Warren K. Laskey, chief of cardiology at the University of New Mexico, Albuquerque. Thoratec studied the HeartMate II in 126 patients in the pivotal study, conducted at 26 sites. As with previous trials of bridge-to-transplant devices, the Thoratec HeartMate II study was prospective and not randomized. Six such devices have been approved, including right, left, and biventricular assist devices and a temporary artificial heart. Unlike those devices, the HeartMate II was subject to a new FDA performance goal that was set in 2002. That goal was defined as survival of the patient to transplant or 180 days of left ventricular support while remaining listed for a transplant as status 1A or 1B. According to the FDA criteria, the HeartMate II did not meet the definition of success: getting the one-sided 95% lower confidence limit of the true success rate to exceed 65%.In all, 89 (70%) of the 126 patients were considered a total success: 72 received transplants, 4 recovered, and 13 were supported for 180 days while listed. This resulted in a lower confidence limit of 64%. Although Thoratec missed the statistical cut-off, the advisory committee members said they believed that the device had shown clinical effectiveness. Safety was comparable to that of other devices, including Thoratec’s two approved bridge-to-transplant devices, the HeartMate VE and the IVAD, said the FDA. There were 29 deaths; 6 patients died of sepsis, 5 died of ischemic cerebrovascular events, and 4 died of multisystem organ failure. One death was considered to be related to device failure. In terms of serious adverse events, 59% of patients (74) had a bleeding episode, and 29% (37) required surgery to stop the bleeding. Stroke occurred in 9% (11) of patients, and sepsis in 20% (25) of the group. Eighty patients had reoperations; 73% were in the first 30 days, according to the FDA. The most common reason for another surgery was bleeding. Bleeding was of concern to Dr. L. Henry Edmunds Jr., a thoracic surgeon and ACS Fellow at the University of The small size and light weight of the P e n n s y l v a n i a , HeartMate II make it simpler to implant Philadelphia, and Dr. than earlier ventricular assist devices. John C. Somberg, chief of clinical pharmacology at support, according to the FDA. And, with primary end point Rush University Medical Center, Chicago. Dr. Edmunds pushed data available on 58 of the pafor a prescriptive protocol in the tients, so far, only 55% met the label for anticoagulation, but his FDA’s statistical cut-off for sucmotions were not approved by cess, according to the agency. Despite unanswered questions, the committee. Dr. Somberg also was cautious with his vote to ap- panelists felt that the device prove the HeartMate II, noting, should be available. “This is an “There’s a lot of science to be in- important new technology,” said vestigated here, especially prob- Dr. Richard L. Page of the University of Washington, Seattle. lems related to bleeding.” “This is an exciting device beIn the ongoing continued access protocol study, 2 of the 138 cause of its small size and ability patients enrolled have required a to be implanted in many more HeartMate II replacement or ex- patients,” said Dr. Norman S. change to another device be- Kato, an ACS Fellow in private cause of pump thrombosis. Both practice at the Cardiac Care Medpatients died while they were on ical Group in Encino, Calif. ■ Preoperative Radiation Boosts Esophageal Cancer Survival BY JANE SALODOF MACNEIL Else vier Global Medical Ne ws L O S A N G E L E S — Neoadjuvant radiotherapy improves esophageal cancer survival by a full year but usually is not used prior to esophagectomy, according to a population-based review of 1,030 patients who had surgery from 1998 through 2003. Median Survival of Esophageal Cancer Patients 30 months 18 months Preoperative radiation (n = 446) Surgery alone (n = 584) Note: Based on a study of 1,030 patients. Source: Dr. Ballonoff Patients given preoperative radiation had a median survival of 30 months, compared with 18 months for those treated with surgery alone. The survival benefit of preoperative radiation was significant, with a hazard ratio for death of 0.61 (P = .0001), and it held up in multivariate analysis (HR 0.66, P less than .0001). Neoadjuvant radiation similarly led to longer survival in a subgroup analysis that eliminated patients who died within 4 months of diagnosis, Dr. Ari Ballonoff reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology. When these patients were dropped from the sample, median overall survival remained at 30 months for those given neoadjuvant radiation but increased to 22 months for those treated with surgery alone. Although the hazard ratio favoring neoadjuvant radiation edged up to 0.80, the difference remained significant (P = .0123). Yet only 446 patients—just 43% of the population—received neoadjuvant radiation before esophagectomy, while the majority, 584 patients, had only esophagectomy. This finding was a surprise, according to Dr. Ballonoff of the radiation oncology department at the University of Colorado Comprehensive Cancer Center, Aurora. The year 1998 was chosen as the start of the study, he explained, because it followed by more than a year the publication of a randomized trial reporting a survival benefit when patients received chemoradiation prior to surgery (N. Engl. J. Med. 1996;335:462-7). Moreover, the investigators expected all therapy after that date to use modern radiation techniques and doses. Dr. Ballonoff and his colleagues plumbed the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database for their study. They selected patients with T2-4N0-1M0 adenocarcinoma or squamous cell carcinoma of the esophagus who underwent curative surgery during the 6 study years; the analysis excluded those who had multiple primary tumors or postoperative radiation therapy. About half of the 1,030 patients were under age 65, 80% were men, 73% had T3 or T4 disease, half had positive lymph nodes, 73% had adenocarcinoma histology, and 44% had more than 10 lymph nodes dissected. Since the SEER registry does not include information on systemic therapies, no definitive statement could be made. Nonetheless, Dr. Ballonoff said he felt certain that a large proportion of patients recorded as receiving neoadjuvant radiation actually received neoadjuvant chemoradiation. Along with preoperative radiation, factors favoring survival in multivariate analysis were age under 65 (HR 0.82, P = .0197), female gender (HR 0.78, P = .0240), T2 stage (HR 0.79, P = .0191), N0 nodal status (HR 0.46, P less than .0001), adenocarcinoma histology (HR 0.73, P = .0009), and having more than 10 lymph nodes dissected (HR 0.73, P = .0003). Dr. Ballonoff cautioned that a retrospective study alone should not change clinical practice. He added in an interview that the findings nonetheless raised questions about standard treatment of esophageal cancer: Did some patients live in areas where radiation therapy was not an option? How many patients were referred to a radiation oncologist before they underwent resection? “I doubt 57% of these patients would have been told by the radiation oncologist that they didn’t need radiation,” he said. “The thing is, probably the radiation oncologist had never seen these patients.” ■ ELSEVIER GLOBAL MEDICAL NEWS REPRINTED WITH PERMISSION FROM THORATEC CORPORATION
For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.