By Dr. David Hewitt, Vice President of Medical and Scientific Affairs, INC Research/inVentiv Health Clinical Division
The third day of ASCO highlighted the science and remarkable advances emerging from the new immunotherapies, but excitement was tempered by concerns over cancer costs.
The plenary session began with a lecture by Dr. James Patrick Allison of M.D. Anderson, and a review of his work in immunotherapy that started in 1995. This work revolutionized cancer treatment, with three new IO drugs on the market and more in development. His talk laid the foundation for Dr. Jedd D. Wolchok of Memorial Sloan Kettering who presented the much-anticipated results from a Phase III randomized trial comparing the efficacy and safety of Bristol Myers Squibb’s nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment-naïve patients with advanced melanoma.
These results that were reported confirmed expectations that the combination of two checkpoint inhibitors would be significantly more effective than monotherapy in treating advanced melanoma.
Patients were randomized to NIVO alone, NIVO plus IPI or IPI alone. Patients were stratified based on PD-L1 expression, BRAF status, and AJCC M stage. The primary endpoint was progression free survival (PFS) and overall survival.
The median PFS was 11.5 months for the NIVO + IPI combination, better than 6.9 months for NIVO alone and much better than 2.9 months for IPI alone. In patients with PD-L1 expression ≥ 5% the median PFS was 14.0 months for both NIVO alone and in combination with IPI, but only 3.9 months for IPI alone. The overall response rate was 57.6% for the NIVO + IPI combination, 43.7% for NIVO alone, and only 19.0% for IPI alone. The median change in tumor burden decreased by 51.9%, 34.5% and 5.9% in the combination treatment, NIVO alone and IPI alone arms respectively. The median duration of response was not reached by any of the three groups, illustrating the effectiveness of the drugs. Data on the overall response rate will be released later. Bristol Myers Squibb has an ongoing expanded access program for patients on combination therapy.
There were no treatment-related deaths. Immune-related adverse events (AE) were similar to those seen in previous studies and were manageable. Most interesting, of the 67% who developed an immune AE, 50% continued to improve after treatment was discontinued.
These results, the investigators said, suggest that the combination of NIVO with IPI should be used in treatment-naïve patients with advanced melanoma.
Dr. Michael B. Atkins of Lombardi Comprehensive Cancer Center, in discussing the results, said the PD-L1 biomarker is weak due to a number of factors and stressed the need for better, validated biomarkers.
Noting the higher AE rate in the combination arm, Atkins stressed the need to base therapy on patient status and suggested using the monotherapy in weaker patients unable to tolerate higher adverse events.
These results will definitely encourage investigators to assess other combination therapies that combine checkpoint inhibitors with conventional chemotherapy, vaccines, radiation, hormonal therapy, anti-angiogenesis therapies, as well as other checkpoint inhibitors.
Shifting gears, Dr. Leonard Saltz of Memorial Sloan-Kettering Cancer Center took the podium to take on the subject of drug pricing, quoting everyone from Winston Churchill to Dr. Seuss. Building on previous comments he has made to The New York Times and 60 Minutes, Saltz called on his colleagues in the medical community to put value at the heart of treatment decisions and question the price of drugs.
He praised the “basic science (that) has been elegantly translated into drugs that benefit patients today” and told attendees “as a clinician I want these drugs for my patients.”
But, he quickly added, “These drugs cost too much. There is an enormous amount of benefit from these drugs but value is not the same as benefit. We can’t realistically assess value without talking about costs.” Value includes considering not only drug toxicity, but also what Saltz calls “financial toxicity.”
Pointing to the Nivolumab + Ipilimumab study, he noted that the cost of the regimen for an American patient weighing 176 pounds would be $295,556 a year, or about $60,000 out of pocket for an individual Medicare patient.
“Why are cancer drugs so high?” Saltz asked. “Current pricing models are not rational but simply reflect what the market will bear.”
As a society, it is projected that annual costs for cancer care will increase to $173 billion by 2020, an increase of 40% over 2010, according to ASCO. At the same time, demand for cancer care services is significantly growing as the U.S. population ages.
Saltz said the rising costs cannot be maintained and pointed to the U.S. system of regulation and oversight as “sustaining the unsustainable.” The U.S. Food and Drug Administration is forbidden by law from considering price, he said, while the U.S. Center for Medicare and Medicaid Services is obligated to buy what the FDA approves and is forbidden from negotiating price. Instead, he said, they are struggling to restrict use. He blamed Congress for creating a clear conflict of interest in allowing physicians to profit from marking up the sale of chemotherapies to patients.
“There must be some upper limit on how much we can afford, as a society, to pay to treat each patient with cancer. We need to be willing to discuss what that limit might be. We need to encourage, rather than suppress discussion of value and cost in cancer care and we must be willing to search for the tipping point on value,” he said.
He said the discussion must engage industry, government, patients, payers and the medical community.
While the debate takes place, oncologists need to talk with patients about costs and benefits. “We must embrace our responsibility to deliver high value, cost-effective care,” he said.
ASCO has been developing a “value framework” to serve as a tool for physicians to use in speaking with patients about the relative value of treatment options. The tool will help physicians and patients consider individual circumstances, the best available information on a particular treatment’s effectiveness, the severity of expected side effect and the treatment’s cost. The framework is to be published in June in the Journal of Clinical Oncology.
Saltz strongly advocated lifting the ban on government price negotiations and referenced discussions over value that have been taking place at this year’s ASCO around pay-for-performance pricing, indication-specific pricing, tiered coverage and providing the first 8-12 weeks of treatment gratis until it is clear that a therapy is working.
“This is a big problem and it is our problem,” he said. “All of us need to urgently engage in active, open and constructive discussions to find fair and practical pricing.” Quoting Winston Churchill, Saltz concluded, “You can always count on Americans to do the right thing after they’ve done everything else.”
INC Research/inVentiv Health is a top-tier professional services company that accelerates the clinical and commercial success of our clients. We provide best-in-class clinical development and comprehensive commercialization services, seamlessly linking the capabilities of a leading, global Clinical Research Organization (CRO) with a unique Contract Commercial Organization (CCO).