One hurdle that leading researchers frequently discuss involves the measures used to evaluate whether an immunotherapy treatment is working in a particular patient. For some patients, tumors may grow before they start to shrink.
Investigators have proposed that new criteria be developed. They cite four patterns of response to immunotherapy that have been associated with favorable outcomes: 2
Shrinkage in baseline lesions, without new lesions
Durable stable disease (in some patients followed by a slow, steady decline in tumor burden)
Response after an increase in total tumor burden
Response in the presence of new lesions
In addition, the SITC and its research partners are developing a standard for classifying the immune status of a tumor.3
would be assessed at the time of diagnosis, along with such established criteria as tumor burden, presence of cancer cells in draining and regional lymph nodes, and evidence of metastases.
The immunoscore would be based on the tumor microenvironment. “Global analysis of the tumor microeinvironment showed that the immune contexture, ie, the nature, functional orientation, density, and location of adaptive immune cells within distinct tumor regions influence the risk of relapse,” the authors said.
While such questions are debated, oncology specialists face other complexities in prescribing immunotherapies. Speaking from his vantage point concerning melanoma, Gajewski noted the impact of cost factors in adopting the therapy.
Ipilimumab is administered intravenously, with a complete course of treatment consisting of four infusions during a three-month period at a cost of $30,000 per infusion, or $120,000 for the series, Bristol-Myers Squibb officials have said.
“I know that many community oncologists are using ipilimumab, but some are not, mainly because of the cost.” Gajewski said in his email. “We are still getting some referrals because small practices can have difficulty paying up front for this expensive drug. So my own view is that the cost of these new biologic agents will have to come down eventually, also to make them more available worldwide.”
Michael D. Becker
MD Becker Partners LLC
Washington Crossing, PA
Over the years, Michael D. Becker has been on several sides of oncology drug development as a financial analyst, investor, and biotechnology entrepreneur, including a stint as president and chief executive officer of the former Cytogen Corporation and VioQuest Pharmaceuticals, Inc. These days, he focuses on cancer immunotherapy at the boutique consulting firm he operates.
Although many companies are developing immunotherapies, Becker said access to investment capital remains dicey for smaller biopharmaceutical companies, particularly because of the rocky road that Dendreon, the Seattle, Washington-based company that developed Provenge, has been traveling.
“There still is a lot of fragility in the marketplace as it relates to cancer immunotherapy,” he said. “Dendreon’s Provenge was a watershed event, the big moment that everybody in cancer immunotherapy was waiting for—to get a product to show clinical benefit and get ultimately approved by the FDA after a lot of failures.
“The fact that we finally had one that got across the finish line was very important, but I think people maybe overestimated just how that was going to change negative perceptions about prior clinical failures and even adoption in the marketplace, and really kind of placed too much importance on that singular product instead of looking at all the recent advancements that have been occurring in the industry,” he said.
Unlike ipilimumab, which is an intravenously administered therapeutic that advances accepted monocolonal antibody strategies, sipuleucel-T is a first-in-class autologous vaccine that has pioneered the use of dendritic cells amid evolving understanding of how immunotherapies work in patients.
Its adoption got off to a slower start than Dendreon executives had anticipated, and there were questions about how oncologists would be reimbursed for the estimated $93,000 cost of a full treatment regimen. In recent months, the company has settled reimbursement questions, trimmed its workforce, and installed new leadership.
In May, Dendreon executives said during a conference call with analysts that Provenge has been gaining acceptance among community oncologists and urologists, with a growing number prescribing the therapy for their patients.