ORLANDO, May 31 — A test widely used to monitor ovarian cancer patients for recurrence did not improve survival despite allowing patients to begin second- and third-line therapy earlier, a large European study showed.

• Explain to interested patients that serial CA125 testing allowed ovarian cancer patients to begin therapy for recurrence earlier than they would have without the testing.
• Note, however, that the earlier therapy based upon testing did not improve survival.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Patients followed with serial CA125 testing began therapy for recurrence about five months sooner than did patients whose treatment was delayed until symptomatic recurrence, Gordon T. Rustin, M.D., reported at the American Society of Clinical Oncology meeting.

Yet, after four years of follow-up, essentially the same proportion of patients had died in each group, Dr. Rustin, of Mount Vernon Cancer Center in Middlesex, England, said.

“Early treatment does not improve survival, and in fact, if anything, slightly decreases quality of life; this is because women who are treated early receive far more chemotherapy,” said Dr. Rustin.

In women with ovarian cancer, serum levels of the cancer antigen CA125 often rise several months before signs or symptoms of recurrent disease. Many oncologists routinely monitor ovarian cancer patients with CA125 testing, although the benefits of monitoring had never been demonstrated in a large prospective clinical study.

So Dr. Tustin and investigators in 10 countries performed a trial to determine whether early treatment based on CA125 test results improved survival in these patients.

The study involved 527 patients who were in complete remission after first-line platinum-based chemotherapy. All the women had a normal CA125 level at study entry.

They underwent CA125 testing every three months, but neither the patients nor their physicians knew the results.

Randomization was triggered if a patient’s CA125 level exceeded two times the upper limit of normal. The patients were assigned to immediate chemotherapy or to delayed treatment based on clinical or symptomatic evidence of recurrence.

The primary outcome was overall survival. After a median follow-up of 49 months, 351 patients (66%) had died.

Patients randomized to immediate chemotherapy started second-line treatment 4.8 months sooner and third-line treatment 4.6 months sooner than did the delayed-therapy group.

Nonetheless, the mortality hazard ratio for early versus delayed treatment was 1.00, reflecting no difference in survival.

“Earlier institution of chemotherapy did not induce a longer remission; this is what so many people out there have been treating patients for,” said Dr. Rustin.

Although the study was negative, the results should allow physicians and patients to make more informed decisions regarding ovarian cancer recurrence and initiation of chemotherapy, he said.

“For the first time women can be reassured that there is no benefit from early detection by routine CA125 testing. They can be told that even if CA125 rises, chemotherapy can be safely delayed until they have signs or symptoms of recurrence. For the first time ever, women now have informed choices to be able to decide.”

In his own clinical practice, most women choose not to have routine CA125 testing. However, Dr. Rustin informs patients about the clinical signs and symptoms of recurrence and encourages them to seek a consultation at the first hint of recurrence.

The study clearly showed that starting therapy early does not make a difference in survival, said Maurie Markman, M.D., a gynecologic oncology specialist at the University of Texas M.D. Anderson Cancer Center in Houston.

However, he believes the study is notable for what the results do not say, as well as for what they do say.

“The study doesn’t say that these women who received therapy either earlier or later did not benefit from that therapy,” said Dr. Markman, who was not involved in the study. “It says that there wasn’t a difference in outcome.”

“The fact that therapy was initiated could very well have had a substantial impact on how long those women lived,” he continued. “It doesn’t say there is no benefit of therapy. It says there is no benefit of starting therapy based solely on this tumor marker.”

The results also do not say that a surveillance strategy for ovarian cancer recurrence, which is routine in the U.S., would be wrong, said Dr. Markman, adding that “there is no evidence that women were harmed by this.”

Dr. Rustin and colleagues reported no competing interests. Dr. Markman disclosed relationships with Bristol-Myers Squibb, Celgene, CTI, Eli Lilly, Genentech, GlaxoSmithKline , Hana Pharmaceuticals, and Ortho Biotech.

Primary source: Journal of Clinical Oncology

Source reference:
Rustin GJ et al. “A randomized trial in ovarian cancer of early treatment of relapse based on CA125 level alone versus delayed treatment based on conventional clinical indicators” J Clin Oncol 2009; 27(15S): Abstract 1.

ORLANDO, May 31 — A drug commonly used to treat breast cancer improves survival in some cases of stomach cancer by about 26%, a Belgian researcher said here.

• Explain to interested patients that trastuzumab (Herceptin) has long been used to treat a specific subtype of breast cancer.
• Note that this study finds a similar subtype in some cases of stomach cancer and shows that the drug is also effective in that setting.
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In a randomized phase III trial, the combination of the monoclonal antibody trastuzumab (Herceptin) and standard chemotherapy outperformed chemotherapy alone, according to Eric Van Cutsem, M.D., Ph.D., of the University Hospital Gasthuisberg in Leuven, Belgium.

It’s the first time the drug — which targets the HER2/neu receptor — has been shown to improve survival in disease other than breast cancer, Dr. Van Cutsem told attendees at the annual meeting of the American Society of Clinical Oncology.

It’s also the “first phase III study to report improved overall survival with a personalized, targeted treatment for gastric cancer,” Dr. Van Cutsem said in a statement.

In the so-called ToGA trial, tumors from 3,807 patients with advanced gastric cancer were tested for HER2, and 22.1% were positive for the receptor, Dr. Van Cutsem reported.

The researchers randomized 594 patients to get standard chemotherapy with or without trastuzumab.

They said median overall survival with the combination was 13.5 months compared with 11.1 months for chemo alone, a difference that was significant at P=0.0048.

After a median of 17.1 months of follow-up the hazard ratio for death was 0.74, with a 95% confidence interval from 0.60 to 0.91, the researchers said.

The overall response rate was 47.3% in the combination arm and 34.5% in the chemo-alone arm, a difference that was significant at P=0.0017.

Safety profiles were similar between the arms, the researchers found, including the rate of symptomatic congestive heart failure. Asymptomatic left ventricular ejection fraction decreases were reported in 4.6% of patients in the combination arm and 1.1% in the chemotherapy alone arm.

Although it’s difficult to make such comparisons, the “gastric data is clearly as strong as in breast cancer,” according to David Schenkein, M.D., of Genentech, a subsidiary of Roche, which makes the drug.

In advanced HER2-positive breast cancer, he said, the pivotal trial showed improved median survival of 25.1 months, compared with 20.3 months for the chemotherapy arm, a 25% improvement in overall survival.

ASCO President Richard Schilsky, M.D., of the University of Chicago Medical Center, said the study is a “great example of the whole concept of personalized medicine.”

“Until these data came out,” he said, “we didn’t know we had to think about two different molecular subtypes of stomach cancer — HER2-positive and HER2-negative.”

The finding is important and may herald clinical use of the drug in HER2/neu-positive gastric cancer, according to Leonard Saltz, M.D., of Memorial Sloan-Kettering Cancer Center in New York City.

“It would not make sense to expose every gastric cancer patient to trastuzumab,” he said. “However, for those whose tumors express the target for trastuzumab, adding that drug to the treatment regimen makes sense.”

But, Dr. Saltz said, there are “a few caveats to keep in mind.”

He noted that the study regimen does not involve replacing chemotherapy, so that trastuzumab “adds, albeit modestly, to the side effects that patients must endure.”

Also, he said, “we must be careful not to confuse the term ’significant’ with ’substantial’.” The survival improvement is 2.7 months or 81 days — “modest progress, not ’substantial’ progress, from a clinical perspective,” Dr. Saltz said.

Other caveats, he said, include the cost of the drug and HER2 testing, which mean the “cost of this modest progress is going to be quite substantial.”

Len Lichtenfeld, M.D., of the American Cancer Society, said the study is “interesting” but agreed that the “gain is modest in terms of the number of months of increased survival.”

On the other hand, he said, “it is important to remember that gastric cancer is difficult to treat, with currently available therapies providing limited success.”

The study was supported by Roche. Dr. Van Cutsem reported financial links with Roche. Some members of the research team are employed by the company. Dr. Saltz reported financial links with Amgen, Bayer, Bristol-Myers Squibb, Genentech, ImClone, Merck, Pfizer, Roche, Taiho Pharmaceuticals, and YM BioSciences. Dr. Lichtenfeld is an employee of the American Cancer Society.

This article was developed in collaboration with ABC News.

Primary source: Journal of Clinical Oncology

ORLANDO, May 31 — A vaccine that uses cancer cells against themselves significantly slows the progress of a deadly form of blood cancer, a researcher said here.

• Explain to interested patients that despite advances in therapy, follicular non-Hodgkin’s lymphoma remains almost invariably fatal.
• Note that this study found that a therapeutic vaccine administered after chemotherapy-induced remission can prolong the period before disease recurs.
• Note, too, that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

In patients with follicular non-Hodgkin’s lymphoma, the vaccine — dubbed BiovaxID — nearly doubled the time before the disease recurred, compared with a control drug, according to Stephen Schuster, M.D., of the University of Pennsylvania School of Medicine in Philadelphia.

The therapeutic vaccine is tailored to each patient’s cancer and given with a drug that stimulates the immune system, Dr. Schuster said at the annual meeting of the American Society of Clinical Oncology.

“We’ve now moved into an era where we can safely use a patient’s immune system to effectively fight follicular lymphoma and enhance the response to conventional chemotherapy,” Dr. Schuster said in a statement.

There are about 65,000 new cases of non-Hodgkin’s lymphoma diagnosed each year in the U.S., and even with aggressive chemotherapy and recent advances in therapy, the disease is almost uniformly fatal.

In the follicular form of the disease, 90% of patients die within seven years of diagnosis.

The vaccine itself is made by extracting cells from lymph nodes and identifying a cancer marker — an “idiotype” — that is unique to each patient, Dr. Schuster said.

The idiotype is then fused with an immune stimulant called keyhole limpet hemocyanin, or KLH. Finally, the combination is administered along with another immune stimulant, granulocyte-macrophage colony-stimulating factor, or GM-CSF.

In this study, the researchers studied 117 patients who had been treated with standard chemotherapy, achieved a complete response, and then maintained that response for at least six months.

They were randomized to get the therapeutic vaccine or the KLH immune stimulant alone, acting as a control drug. Both were administered with GM-CSF.

All told, 76 patients got the vaccine and 41 got the control drug, Dr. Schuster said.

After a median follow-up of 56 months, the median time to relapse for patients getting the vaccine was 44.2 months, compared with 30.6 for those in the control group. The difference was significant at P=0.045 and yielded a hazard ratio of 1.6, the researchers found.

No serious adverse events were associated with the vaccine, Dr. Schuster said.

“The problem with that kind of lymphoma is that chemotherapy doesn’t actually cure anybody,” said ASCO President Richard Schilsky, M.D., of the University of Chicago Medical Center, who was not involved in the study.

“They all go into remission with chemotherapy but they all relapse,” Dr. Schilsky said. “Each time you use chemotherapy, the remission lasts less time and eventually they just become refractory.”

So, he said, “the longer you can keep them in remission the better.”

The researchers commented that the approach might also be useful in other forms of B cell cancer, such as chronic lymphocytic leukemia. Dr. Schilsky noted that — unlike other forms of cancer — the B cell cancers display a range of cell surface proteins that are distinctive.

“That’s what makes this a feasible approach, because you can use that to develop a unique vaccine for each kind of lymphoma,” he said.

The study was supported by Biovest International. The researchers reported financial links with Accentia Biopharmaceuticals, Biovest International, Antigenics, Biogen Idec, Genentech, and Xeme Biopharma.

Primary source: Journal of Clinical Oncology

Source reference:
Schuster SJ et al. “Idiotype vaccine therapy (BiovaxID) in follicular lymphoma in first complete remission: Phase III clinical trial results” J Clin Oncol 2009; 27(15S): Abstract P2.