Treatment Vaccines for Cancer Perform Well in Clinical Trials
Treatment vaccines that boost the immune system’s response to tumors may have important clinical benefits for patients with various types of cancer, according to results from several clinical trials presented at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando.
To many in the field, the findings represent an emergence of sorts for therapeutic cancer vaccines. Treatment vaccines have been the subject of intense study for more than 2 decades, but they have produced little in the way of FDA-approved cancer treatments. That could change based on the recent clinical trial results.
“The field has been getting more attention, and with these recent trials I think we’ll see a surge of interest in immunotherapy leading to much needed additional therapeutic options that improve survival without significant toxicity,” said Dr. James Gulley from NCI’s Center for Cancer Research, who is leading a number of clinical trials using treatment vaccines.
Therapeutic cancer vaccines, added Dr. Jeffrey Schlom, chief of NCI’s Laboratory of Tumor Immunology and Biology, have had a hard time gaining acceptance in part because they represent a different care paradigm. “A vaccine is the only therapeutic modality that doesn’t work on the tumor. It works on the patient’s immune system to keep the tumor in check,” he said.
Among the results that generated intense interest at the meeting were those from a large, phase III clinical trial of a vaccine called BiovaxID to treat patients with follicular lymphoma, the second most common type of non-Hodgkin lymphoma. Dubbed an idiotype vaccine, BiovaxID is customized for each individual patient from tumor cell proteins taken from tumor biopsies.
The trial, BV301, randomly assigned patients who had a sustained (6-month) complete response to standard chemotherapy to either BiovaxID plus two other immune-stimulating agents (GM-CSF and KLH) or the two immune-stimulating agents alone. Patients who received the vaccine had a 47 percent improvement in progression-free survival (survival without tumor growth) compared to those who only received the immune stimulants, 44.2 months versus 30.6 months, reported lead investigator Dr. Stephen J. Schuster from the University of Pennsylvania School of Medicine.
Two previous phase III trials using a similar vaccine in patients with follicular lymphoma had negative results. That may be because those trials included patients who had partial responses and stable disease, as well as complete responses, explained Dr. Ronald Levy of the Stanford University School of Medicine, during the meeting’s plenary session. In contrast, the analysis from BV301 was limited to patients who were “the best of the best”—that is, only those with sustained complete responses.
Drs. Levy and Schuster agreed that it’s still unclear how this vaccine would work in the context of the current standard of care for follicular lymphoma, which changed during the course of the BV301 trial and now includes the monoclonal antibody rituximab (Rituxan). Calling the trial a “qualified success,” Dr. Levy said other clinical trials will be needed to establish the best use of the vaccine in follicular lymphoma.
Another phase III trial that generated interest at the meeting used a long-studied peptide-based vaccine (a peptide is a small segment of amino acids) to treat patients with metastatic melanoma, a deadly skin cancer for which treatment advances have been rare.
When combined with IL-2, the standard of care for metastatic melanoma, treatment with the gp100:209-217(210M) peptide vaccine doubled the response rate of patients compared to those who received IL-2 alone, 22.1 percent versus 9.7 percent, reported one of the trial’s leaders, Dr. Patrick Hwu from the University of Texas M.D. Anderson Cancer Center. Response rate was the trial’s primary endpoint. There was a slight improvement in progression-free survival, 2.9 versus 1.6 months, and the preliminary analysis suggests a trend toward improved overall survival.
Calling the improvement an “important finding,” Dr. Lynn Schuchter from the University of Pennsylvania’s Abramson Cancer Center said the results are grounds for optimism. Therapeutic vaccines have been tested in melanoma for more than a decade with little success. Now there is a positive phase III clinical trial.
“It makes us think maybe this is a combination that will work,” she said.
There are a number of other immune stimulating agents under study that can be used in combination with the peptide vaccine, Dr. Hwu said. The next steps, he noted, will be to conduct another large trial to replicate these findings and continue testing different combinations.
In a smaller, phase II clinical trial with 122 patients, treatment with a vaccine developed at NCI, called Prostvac, showed a more than 8-month improvement in overall survival in patients with indolent metastatic prostate cancer. This is the second phase II trial to show a nearly identical benefit of Prostvac, which is comprised of two virus-based “vectors,” in the same patient population, explained Dr. Schlom. A larger, phase III trial is expected to begin in 2010.
The field is already moving toward combining different therapeutic vaccines, Dr. Schlom continued, with the idea of using them in earlier-stage disease, where he believes they will be most effective.