Value Propositions - September 2014

September 2014, Vol 5, No 7

Study Identifies 2 Novel Mutations Responsible for Lung Cancer Resistance and How to Overcome It
The discovery of 2 new mutations in patients with non–small-cell lung cancer (NSCLC) that are the cause of resistance in some patients whose disease does not respond to current targeted therapies has charted the way for overcoming resistance in this patient population. This discovery comes from a new study (funded by the National Cancer Institute and the Japan Society for the Promotion of Science) that investigated the reason why ALK-positive lung cancer becomes resistant to alectinib, a new-generation ALK inhibitor that was recently approved in Japan and received a Breakthrough Therapy designation by the FDA.

“We discovered two novel mutations that have not been described before in patients with NSCLC, and these mutations conferred high-level resistance to alectinib,” said lead investigator Alice T. Shaw, MD, PhD, thoracic oncologist, Massachusetts General Hospital Cancer Care, Boston. “Another equally important finding from this study is that we were able to find a way to overcome this type of resistance…using another next-generation ALK inhibitor, ceritinib.”

Dr Shaw added, “There are eight next-generation ALK inhibitors that have entered the clinic, and our results show that ALK-positive lung cancer patients may benefit from multiple, sequential ALK-inhibitor therapies depending on the underlying resistance mechanism.”

The discovery of these 2 novel mutations, and how to overcome the resistance they cause, reinforce the value of genomic testing and personalized medicine in the clinical practice setting.

American Association for Cancer Research press release; September 16, 2014

Kaiser Permanente Implements Value-Based Care/Payment Model
In an exclusive interview with FierceHealthPayer, Jack Cochran, MD, Executive Director of the Permanente Federation, discussed the benefits in implementing value-based care and a payment model at Kaiser Permanente, which represents a partnership between a healthcare delivery entity, hospitals, and the Kaiser health plan. “For our care to be value-based, we think of how many people we have to take care of, and then we figure how much it’ll cost….We think in terms of the entire package, the physicians and their staff, and decide how much we will need to expense them,” Dr Cochran said.

The move toward value-based payment required an enhanced focus on data measurement across the entire health plan. Establishing tools to measure data and care transparency is crucial for improving outcomes, which, in turn, can reduce costs. “Doing the right thing will also be the best thing to make sure care is affordable,” he said.

Kaiser has moved away from the fee-for-service model, in which providers are paid for each service rendered, and is moving to value-based payment (VBP). “At Kaiser Permanente, under a VBP model, we look at the process of care, which may not entail classically codeable events. We pay them [providers] for their intellect, not for what is just codeable,” Dr Cochran elaborated. He noted that avoiding misuse and errors will help to generate the savings in healthcare that everyone is concerned about. The quality of care must be the focus of healthcare for all, he said. “The entire industry needs to shift its focus on quality at a reasonable cost for families.”

Dori Zweig, FierceHealthPayer; August 1, 2014

UK National Health Services Increases Funds for Cancer Drugs Research
At a time when the US government has downsized its financial support for cancer research, the UK’s National Health Services (NHS) announced it was increasing the annual funding it provides to the Cancer Drugs Fund from £200 million to £280 million.

“We welcome the moves the Government is taking to increase access to innovative cancer medicines. It is critical that our systems for making new drugs available on the NHS take into account how innovative a drug is, as opposed to simply giving the green light to ‘me too’ drugs that replicate the functions of others already available,” said Paul Workman, Interim Chief Executive of the Institute of Cancer Research, London. “Making more money available to the Cancer Drugs Fund and using it in a more targeted way could significantly improve access to important new treatments like abiraterone, which was discovered at The Institute of Cancer Research, and was recently turned down by NICE [National Institute for Health and Care Excellence] for use in patients pre chemotherapy.”

The Institute of Cancer Research press release; August 28, 2014

NIH Launches Second Personalized Medicine Clinical Trial in Lung Cancer
The National Institutes of Health (NIH) announced the launch of the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials (ALCHEMIST) to investigate the value of targeted therapies in patients with early-stage lung cancer associated with genetic mutations.

ALCHEMIST is the second personalized medicine clinical trial launched as part of the new National Clinical Trials Network (NCTN), which is supported by the National Cancer Institute (NCI). The first NCTN trial was launched in June 2014 and targets patients with advanced squamous-cell lung cancer.

ALCHEMIST includes 3 complementary component trials that together will provide important information for patients with few treatment options. The 3 components are (1) a screening trial, (2) a treatment trial for patients with EGFR mutations, and (3) a treatment trial for patients with rearrangements in the ALK gene. Each trial is listed as an independent trial at trials (ie, NCT02194738, NCT02193282, and NCT02201992, respectively).

“We believe that the findings from ALCHEMIST will not only help answer an important question about the addition of targeted therapies in earlier-stage disease, but will also help us in understanding the prevalence and natural history of these genomic changes in earlier-stage lung cancer. We also hope to gain a better understanding as well regarding the genetic changes in the tumor at the time of recurrence,” said Shakun Malik, MD, Head of Thoracic Cancer Therapeutics in the Clinical Investigations Branch of the NCI. “The findings will help to define clinical, biologic and molecular behaviors of this type of lung cancer.”

All patients enrolled in the ALCHEMIST component trials will have to undergo surgical removal of their tumors. Eligibility criteria include having been diagnosed with lung adenocarcinoma or similar types of lung cancer, and receiving standard therapy after the surgical removal of the tumor that consists of chemotherapy with or without radiation therapy, as prescribed by the patient’s physician.

In the ALCHEMIST screening trial, the surgically removed tissue will be tested for changes in the ALK and the EGFR genes. Patients with EGFR mutations or rearrangements of the ALK gene will be enrolled in 1 of the 2 randomized, placebo-controlled treatment component trials according to their specific genetic alterations.

The 2 treatment trials will evaluate the value of using a therapy that has been approved by the FDA for patients with lung cancer and a genetic alteration. The specific therapies to be investigated are erlotinib (Tarceva), which is FDA approved for patients with EGFR genetic mutations, or crizotinib (Xalkori), which is FDA approved for patients with rearrangements in the ALK gene. Although these 2 agents are indicated for the treatment of patients with advanced lung cancer and the respective genetic alterations, it is not known whether they can prevent cancer recurrence in individuals who are free of disease (in this case, after their tumor was surgically removed).

The goal is to determine whether erlotinib or crizotinib will prevent lung cancer recurrence, as well as prolong survival. The trials also involve other clinical aspects that will address survival, DNA sequencing, and genomic analysis. The intent is to enroll 800 patients who fit the eligibility criteria. Patients will be followed up for 5 years.

National Institutes of Health press release; August 18, 2014

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