The OBR Blog

March 22, 2012 - 03:03 pm Posted in Featured comments1 Comments


Andrew Pecora, MD, FACP, CPE, is President of the newly formed Regional Cancer Care Associates—a statewide group of 76 oncologists who have consolidated their practices into a new oncology network in New Jersey. This new network is supported by 500 employees at 20 cancer care delivery sites that stretches from Cape May in the south all the way up to the northern part of the state, and includes the state-of-the-art John Theurer Cancer Center at Hackensack University Medical Center where Dr Pecora is vice president of cancer services. Size matters in today’s environment, and the new network provides care to more than 17,000 new patients annually, in addition to the 230,000 patients that already participate in the provider network. Regional Cancer Care Associates is a “value-based” cancer care network that will allow the network to bargain as a group with insurance companies and drug companies to provide quality cancer care to patients while reducing the cost of that care.

Although each participating practice will retain autonomy in terms of making specific medical decisions for the care of their patients, a doctor-dominated board of trustees will standardize that care—meaning, for example, that the trustees will decide how many diagnostic tests are to be ordered or decide on the effectiveness of certain chemotherapies for treatment. When we heard about the creation of a new network, we thought it would be important to discuss the details with Dr. Pecora.

OBR: First, what was the motivation that got you to the point where you wanted to combine all these forces under one umbrella?

AP: It was a number of things. I wish I could explain it all in a sound bite, but I can’t. Things have occurred over the last couple of decades that have now come to a focal point, and to me, they’re pretty frightening. Societies have invested hundreds of billions of dollars in disease research and clinical trials over the past 60 years to find new methods of treatment, and have been unbelievably successful in not all, but some of these disease areas. As an example, we’ve been able to change the paradigm of cancer care where if a patient had metastatic breast cancer two decades ago she was gone in 2 or 3 years. Today, those patients can live 15, 20 years after diagnosis, and that kind of care is only accelerating. And that’s just cancer. Cardiologists and infectious disease specialists are both doing an amazing job as well in preventing people from dying prematurely from cardiac disease and infections.

We have more new, expensive therapies being developed every day and more people using the drugs. But with all these great advancements, comes the issue of the cost. Combine that with the general state of the U.S. economy, and all the demands to modulate the increased growth rate of healthcare costs and there’s a perfect storm brewing.

I started evaluating the economic pressures from a macro and micro level, and working in a consulting role with some payers, just trying to understand what it all means when it just hit me like a ton of bricks: The Great Britain health system is not “very nice”—there are drugs that work that are not being approved there. Meanwhile, here in the US we are talking about “death panels”, we have the emergence of ACOs (where we’re trying to empower primary care doctors), and hospitals are either struggling to stay in business, or are buying up practices, or are being bought by insurance companies. It all points in one direction—if you want to remain relevant, you’d better be big—and as big as we are at the John Theurer Cancer Center, we’re still not big enough to protect ourselves against market forces.

When it dawned on me that we weren’t big enough in the number of patients we saw, even though we’re one of the biggest providers of cancer care in the country, I started talking to other cancer doctors in the state about merging. What I learned isn’t surprising. We’re all concerned about our well being, but we’re also passionate about our profession and we cringe at the thought that, “I’ve waited all my career to have these wonderful drugs to offer people, and now I may not be able to afford them, or even worse, someone else is going to tell me I can’t use them.”

I know that is a little long-winded, but that was the genesis of Regional Cancer Care Associates. All those forces lining up lead me and several other oncologists, to go around the state and talk to our colleagues. The message we had resonated with them and we started building the network.

But that was only part one. Part two was the difficulty of coming up with a business plan that made sense. That took time and work, but we did it, and we were able to close on 10 practices and 74 doctors in 4 months, and get all the payers to go along with it, including Medicare.

OBR: When you say “remain relevant,” do you mean autonomous?

AP: No, I don’t think anyone’s going to be autonomous so let me define relevant. Relevant means that you’ll be at the decision table discussing how cancer care is going to be delivered, wherever that table is. You’re not going to be told by ACOs, “guess what, we don’t want to treat metastatic pancreatic cancer anymore, everyone has to go on hospice.” I’m not saying this would ever happen, but looking at what’s happening in Great Britain, I get very concerned about the future of cancer care here.

I’m worried about what happens if we shift to a single-payer health care system or what happens to cancer care delivery if we move to some sort of big integrated model. Being relevant means being able to help shape delivery of cancer care in a new model whatever that is.

OBR: How grassroots was your idea to join all these forces under one umbrella?

AP: It was like running for office. I drove around the state and went to every office, went to their partners meetings, presented, took their questions, looked them in the eye and suggested that this is what we have to do. With something this important, I felt it was necessary to use a grassroots approach.

OBR: Do you anticipate adding more offices?

AP: Yes. We’re going to probably add another 30 to 40 docs, another 5 or 7 offices because we have promised some of our local payers that we would have an office within 30 minutes of any patient in the state. We aren’t looking to leverage the size of our network and get paid more per unit service, but on average we want to make sure that if a practice or physician joins our network, he or she won’t be hurt economically.

OBR: It is impressive that you can do that. We hear a lot about office closures due to economics. Your network intends to leave the rural offices open through the strength of the network?

AP: Absolutely.

OBR: Please tell us about the board of trustees that is helping guide the clinical decision making?

AP: The board consists of partners (or members) from each of the practices. Their participation is determined by a ratio based on the number of doctors that are in that group. We also plan to add independent board members that are knowledgeable of today’s dynamics. For example we plan to add someone from the healthcare industry, a patient advocate, and an expert physician that’s not part of the network. We intend to be transparent about everything we do.

When we make a decision that has a clinical consequence, we’re not going to hide it. We’re going to post it and we’re going to provide an explanation for the decision. The idea is to get people comfortable with the fact that there is a way to mitigate the growth of healthcare expenditures, in cancer, and yet continue to offer the highest quality, cutting-edge care. That’s our mission; that’s why we came together.

OBR: You’ve been talking with payers about the network, has anyone asked to participate in the board and help with implementation of pathways?

AP: No payers have asked to be on our board. I don’t think they’d want to be and I’m not sure we would let them because there may be a conflict of interest. I can foresee us getting a payer representative on the board, but probably not someone from New Jersey.

But remember that payers don’t get up in the morning and say “alright, how do we squeeze another 10 base points out of our margin by not paying for things that we should pay for.”
What I want to do is offer payers a solution.

The doctors in our network all have 2 and 3 board certifications—they’re great people that care about the community. They’re the ones up at three in the morning taking care of the 20-year old leukemic. We want to keep these people motivated, just in case it’s one of your kids or family members that get cancer.

Given that kind of expertise and caring, I’m certain payers will work with us to find solutions.

OBR: Thinking of the logistics of the merger of these practices, are you going to try to integrate everybody into the same EMR for example?

AP: We’re going to have to integrate completely to be transparent, and that is part of our strategy. Obviously, an individual patient’s record won’t be transparent, but the outcomes of the care must be transparent to the public. A common EMR for our network practices will help us accomplish that goal.

OBR: You’re already making investments in the network then?

AP: We are, and the good news is that we’re pretty big and our collective revenue is not inconsequential. We have to take some of the revenue and invest it to accomplish our goals. But that challenge is a better one than just staying the way we were and fighting the fight individually.

While trying to keep the hyperbole to a minimum, I can honestly say that I don’t think I’ve ever seen a group of doctors more excited and more re-invigorated in their futures than I’ve seen at these meetings that we’ve had. There was a loss of control, a loss of dignity in the old model. Now I think we all see a possibility that our trade could come back in a way that’s quite rewarding for everyone.

by Don Sharpe

March 15, 2012 - 07:03 am Posted in Featured comments0 Comments

In 2011, five new agents were approved in the U.S. that transformed the field of oncology: Adcetris™ (brentuximab vedotin, Seattle Genetics), Xalkori® (crizotinib, Pfizer), Yervoy™ (ipilimumab, Bristol-Myers Squibb), Zelboraf® (vemurafenib, Roche/Plexxikon, a member of the Daiichi Sankyo group) and Zytiga® (abiraterone, Johnson & Johnson).

• Adcetris™ is an antibody-drug conjugate that delivers chemotherapy directly to CD30-expressing cells. It gained approval in relapsed Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma. Its approval brought a major therapeutic advance to a tumor type that drug developers have largely ignored due to the small market size.

• Xalkori® is an ALK inhibitor that demonstrated spectacular efficacy in non-small cell lung cancer patients harboring EML4-ALK fusion. Although other ALK inhibitors have entered clinical development, none have yet reached Phase III status.

• Yervoy™ is an immunotherapeutic targeting the brake of the immune system called CTLA4. It was the first agent to demonstrate improved overall survival in a Phase III melanoma trial in 30 years. Its main drawback, however, is the immune-related adverse toxicity that requires close monitoring of the patient.

• For melanoma patients harboring BRAFV600E mutation (a key driver of the disease), the approval of Zelboraf® (an inhibitor of BRAFV600E mutant) now offers another treatment option. It demonstrated impressive efficacy, similar to that observed for EGFR mutants and EGFR inhibitors in lung cancer, and marked the beginning of personalized medicine in melanoma.

• Zytiga® is an inhibitor of an enzyme involved in testosterone production in testicular and adrenal tissue. It introduced a new treatment paradigm in prostate cancer by showing that patients previously considered hormone-resistant may still respond to endocrine therapy.

With so many advances in oncology in 2011, other drugs are filling up oncology pipelines with the promise of offering new therapeutic options for patients with unmet needs.

T315I Chronic Myelogenous Leukemia: Will Ponatinib Succeed?
Chronic myelogenous leukemia harboring the T315I mutation represents an important unmet need as it does not respond to currently approved tyrosine kinase inhibitors. Ariad’s ponatinib, a BCR-ABL inhibitor, is the most promising late-stage agent that showed encouraging data at the 2011 American Society of Hematology (ASH) annual conference. Ariad is also developing a companion diagnostic test for the detection of the T315I mutation in collaboration with MolecularMD, which will be key for its success.

KRAS Mutant Colorectal Cancer: Is Indirect Targeting the Only Way to Go?
KRAS mutant colorectal tumors do not respond to EGFR-targeted antibodies. The main problem is that although KRAS mutations are relatively common in colorectal cancer, the KRAS protein itself isn’t an easily druggable target, and all attempts to date have failed. Rather, most of the developmental focus has been on indirect targeting of KRAS through its downstream targets (such as Raf or MEK) or targeting other upstream receptor tyrosine kinases. NKTR-102 (a next generation topoisomerase I inhibitor from Nektar) is currently in Phase II/III development specifically in KRAS mutant colorectal cancer patients. Two other drugs in Phase 2/3 delopment come from Amgen’s pipeline: AMG479 (an IGF-1R antibody) and AMG655 (a TRAIL receptor 2 agonist). Efficacy data has not yet been presented, but if positive, these drugs could finally offer a personalized treatment option for patients with KRAS mutations.

MEK Inhibitors: A New Class of Drugs on the Horizon
MEK inhibitors have gained a lot of attention as potential therapy in BRAF mutant melanoma either as monotherapy or in combination with BRAF inhibitors. At least five MEK inhibitors are in clinical development, although so far GSK1120212 from GlaxoSmithKline is the only one in a Phase 3 program for melanoma harboring V600E/K mutations. If approved, it will face stiff competition from Zelboraf, which captured a significant portion of the BRAF mutant melanoma market after its 2011 launch. Combination with a BRAF mutant inhibitor could represent a better strategy in terms of both efficacy and safety, and GlaxoSmithKline is already exploring this combination approach in a Phase I trial with GSK1120212 and its BRAF inhibitor GSK2118436. Other companies have jumped in to evaluate BRAF/MEK combination, with Novartis conducting a trial with RAF265 and MEK162, and Roche/Daiichi Sankyo conducting a combination trial with Zelboraf and GDC0973.

PI3K Inhibitors: A New Class of Drugs on the Horizon
At least 16 Class I PI3K inhibitors are in clinical development, but some differentiation exists between them – some are pan-PI3K inhibitors, some are isoform-specific inhibitors and some are dual PI3K and mTOR inhibitors. Notably, several PI3K inhibitors are currently in Phase 1/2 trials in endometrial cancer: Pfizer’s PF-04691502, Novartis’ BKM120 and BEZ235, XL147 from Sanofi and Exelixis, and Daiichi’s DS-7423. This is an example of a niche indication that has not really benefited from active drug development until PI3K mutations were identified in these tumors. Several companies are also currently evaluating the combination of PI3K and MEK inhibitors. For example, Roche/Genentech is conducting a trial with GDC0941 plus GDC0973; Novartis with BKM120 plus MEK162, BEZ235 plus MEK162, and BKM120 plus GSK1120212; Pfizer with PF04691502 or PF05212384 plus PD0325901; and GlaxoSmithKline with GSK2126548 plus GSK1120212.

Refocusing Pipelines on Niche Indications
Approval of several targeted therapies over the last decade speaks to the trend that “one size fits all” oncology drugs are becoming a thing of the past. More and more companies are developing therapies for patient segments expressing a specific biomarker within a big tumor type but are also refocusing their pipelines on niche indications that have previously been largely ignored. While patient numbers are smaller, return on investment can still be attractive, especially if the agent demonstrates remarkable efficacy as seen with Xalkori® in EML4-ALK-fusion positive non-small cell lung cancer.

Sarcoma is an example of a niche indication that has enjoyed a lot of clinical activity, with several drugs in Phase III programs. The closest to approval are Votrient® (pazopanib, GlaxoSmithKline) in the refractory setting and Ariad’s ridaforolimus in the maintenance setting, both of which filed regulatory submissions in July 2011. Other drugs with active Phase 3 programs include Sanofi’s AVE8062 (a vascular disrupting agent), Ziopharm’s Zymafos™ (an active metabolite of ifosfamide that is already considered the standard of care for sarcoma), Threshold Pharmaceuticals’ TH-302 (a hypoxia-activated prodrug that releases DNA alkylating agent within hypoxic regions of tumors), Eisai’s Halaven™ (eribulin, a tubulin targeted drug already approved for breast cancer) and Yondelis® (trabectedin, PharmaMar/Johnson & Johnson).

Other drugs in late-stage development pursuing niche indications include Genentech’s Erivedge™ (vismodegib) in basal cell carcinoma and Astellas’ OSI-906 in adrenal cancer. Erivedge™ is an inhibitor of the hedgehog signaling pathway that earned regulatory approval in the U.S. in January 2012. Not surprisingly, other hedgehog inhibitors have entered clinical development, such as LDE225 (Novartis), BMS-833923 (Bristol-Myers Squibb/Exelixis), IPI-926 (Infinity Pharmaceuticals), PF-04449913 (Pfizer), LEQ506 (Novartis) and TAK-441 (Millennium/Takeda). OSI-906 is an IGF-1R and insulin receptor inhibitor and so far is the only drug in Phase III development for adrenal cancer.

Conclusion
Drug developers continue to invest substantial resources behind cancer drugs, and novel mechanistic classes are emerging on the horizon as potential new therapies. Some of these drugs were highlighted above, but Kantar Health’s CancerMPact® Emerging Technologies offer provides a detailed, unbiased evaluation of the overall commercial viability of more than 50 of the most promising cancer agents as well as emerging mechanisms of action in clinical development that will have a significant commercial impact in the next five years. If you would like more information about this offer, please contact us at www.kantarhealth.com/contactus or email info@kantarhealth.com.

By Tatiana Spicakova, PhD, Associate Consultant, Kantar Health

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