ELCC: Immunotherapy for NSCLC Well-Tolerated

By Michael Smith
GENEVA, 26 april 2008-- An immune-boosting treatment for non-small-cell lung cancer patients with completely resected stage IB or II disease is safe and well tolerated, researchers said here. The 44-week results of a phase II study of MAGE-A3, a tumor-specific antigen, also show a nonsignificant "strong signal" in favor of better survival and longer time to relapse, according to Johan Vansteenkiste, M.D., Ph.D., of University Hospital of Louvain in Belgium, and colleagues. The improvements are tending to be similar to those seen with chemotherapy, Dr. Vansteenkiste reported at the European Lung Cancer Conference, although a phase III trial, now underway, is needed to demonstrate efficacy. "Surgical resection is the standard treatment for patients with early stage lung cancer, but after complete resection about 50% will relapse and die from their cancer," Dr. Vansteenkiste said.
He added that post-op chemo improves cure rates, but is "sometimes poorly tolerated by patients recovering from thoracic surgery. In addition, not all patients can withstand chemotherapy."
With MAGE-A3, he said, the reduction in the risk of relapse is currently not significant but is tending to be comparable to that seen with chemotherapy, but with minimal side effects -- mainly injection site reactions and fever over a 24-hour period.
Dr. Vansteenkiste said reactions are similar to those seen with prophylactic vaccines. "That's one of the important things about this approach," he said.
The study included 182 patients, randomized on a two-to-one basis to get either the MAGE-A3 recombinant protein or placebo. The patients were selected to have cancer that expressed the MAGE-A3 protein.
Injections were given over a 27-month period, with the first five given at three-week intervals, then eight given once every three months, the researchers said.
The primary endpoint of the study was disease-free interval, with safety, disease-free survival, overall survival, and assessment of humoral and cellular anti-MAGE-A3 immune response as secondary endpoints.
After a median of 44 weeks of follow-up, Dr. Vansteenkiste and colleagues said:
There were 69 recurrences and 57 deaths.
The disease-free interval hazard ratio was 0.75, with a 95% confidence interval from 0.46 to 1.23, in favor of patients getting the MAGE-A3 protein, although the difference at P=0.127, did not reach significance.
The hazard ratios for disease-free and overall survival were also not significant at 0.76 and 0.81 (also in favor of the MAGE-A3 group) with 95% confidence intervals from 0.48 to 1.21 and 0.47 to 1.40, respectively.
More than 98% of patients given the recombinant protein had an anti-MAGE-A3 IgG antibody response.
T-cell responses were measured in 51 patients and a CD4 T-cell response to MAGE-A3 was seen in 15 of 37 immunized patients (41%), and only in two of 14 patients who got placebo (14%).
Dr. Vansteenkiste said the study was not designed to achieve statistical significance in the efficacy endpoints. "It would be a miracle if, with only 200 patients, you had significance," he said.
Instead, he said, the researchers looked for a "promising signal" that would justify a larger, 2,000-patient phase III trial, which began enrolling patients last year.
The study was sponsored by GlaxoSmithKline the manufacturer of MAGE-A3. Dr. Vansteenkiste reported no conflicts. One of the co-authors is an employee of GlaxoSmithKline Biologicals.
Primary source: European Lung Cancer ConferenceSource reference:Vansteenkiste J, et al "Phase II randomized study of MAGE-A3 immunotherapy as adjuvant therapy in stage IB/II non-small cell lung cancer (NSCLC): 44-month follow-up, humoral and cellular immune response data" ELCC 2008; Abstract 1480.

ASCO: No Survival Benefit for Shark Cartilage in NSCLC

CHICAGO, June 3 -- Adding shark cartilage extract to chemoradiation failed to improve survival in non-small cell lung cancer (NSCLC) patients, results of a government-mandated clinical study show. Patients who received the extract, known as AE-941, along with chemoradiation actually had slightly worse survival times compared with those who received just the standard therapy, although the difference was not statistically significant, said Charles Lu, M.D., of the University of Texas M.D. Anderson Cancer Center in Houston.
"This study represents the first large phase III trial of a shark cartilage-derived pharmaceutical compound," said Dr. Lu at the American Society of Clinical Oncology meeting here.
"Therefore," he said, "current clinical data do not support the routine use of shark cartilage-derived products as anticancer therapies."
For years cancer patients have used over-the-counter shark cartilage compounds, with or without the knowledge of their physicians. Congress responded to the consumer demand with a funded mandate to study shark cartilage's therapeutic potential in cancer.
According to the National Cancer Institute, preclinical studies showed that shark cartilage has antiangiogenic activity and that it shrank or slowed the growth of NSCLC cells. Dr. Lu said results of phase I and II clinical trials suggested that the substance had activity at higher doses in some NSCLC patients.
The NCI-sponsored multicenter trial initially had an enrollment target of 756 patients, but the trial was stopped early because of slow patient accrual. Dr. Lu reported findings on 379 patients with unresectable stage III NSCLC.
He and his colleagues randomized the patients to 120 ml of AE-941 BID or placebo. The AE-941, a water extract of dogfish shark cartilage, was delivered frozen in 120-ml vials that patients thawed and then self-administered.
All patients received induction chemotherapy and concomitant chemoradiation therapy. The primary outcome was survival. When the trial ended, patients who had received AE-941 had a median survival of 14.4 months, compared with 15.6 months for the placebo group (P=0.73). There was also no benefit from AE-941 in any of the sub-group analyses that stratified subjects by gender, stage (IIIA versus IIIB) or chemotherapy regimen.
The study will likely bring down the curtain on a product that entered large-scale clinical evaluation riding the tide of generally favorable data from experimental and small clinical studies. In a move portending the negative outcome of the trial, AEterna Zentaris, the Canadian manufacturer of AE-941, announced in March that it would cease production of the shark cartilage extract.

Minimally Invasive NSCLC Surgery Improves Chemotherapy Deliveries

DURHAM, N.C., April 12 -- Minimally invasive surgery for non-small-cell lung cancer can improve the timely and full-dose delivery of adjuvant chemotherapy, according to researchers here.
Patients who underwent thoracoscopic lobectomy -- compared with the conventional open-chest thoracotomy -- had fewer missed or reduced doses of chemotherapy, found Thomas D'Amico, M.D., of Duke University Medical Center, and colleagues.
A larger proportion of the thoracoscopy patients got 75% or more of their treatment on time and at the planned dose, they reported in the April issue of the Annals of Thoracic Surgery.
"This study showed that patients who had the minimally invasive operation were less likely to experience delays in receiving chemotherapy or a reduction in the amount of chemotherapy we were able to give," Dr. D'Amico said.
"Chemotherapy after surgery has been shown to improve survival in lung cancer patients, so the more effectively we deliver that chemotherapy, the better," he added.
The findings -- some presented last year at the Southern Thoracic Surgical Association meeting in Tucson, Ariz. -- came from a retrospective review of 100 consecutive patients at Duke who had a lobectomy, followed by adjuvant chemotherapy.
http://www.medpagetoday.com/HematologyOncology/LungCancer/tb1/5428