​​Cancer Policy Monitor: July 11, 2017     

Cancer Policy Updates from Capitol Hill     

While Congress has yet to agree on a formal budget resolution, it continues to move ahead on fiscal year (FY ) 2018 spending bills through the Committee process. The House Appropriations Labor, Health and Human Services (HHS), Education, and Related Agencies Subcommittee, chaired by Rep. Tom Cole (R-OK), is scheduled to meet on Thursday, July 13 at 4:30 p.m. to mark up bills in its jurisdiction, which includes National Institutes of Health (NIH) and National Cancer Institute (NCI) funding. Chairman Cole has made it clear on several occasions that medical research will continue to be a top priority in his bill, and that he hopes to provide another increase for the NIH.

On the Senate side, there have been no signs of movement on appropriations bills, likely because the Senate is currently busy with the health care reform debate. However, on June 22, the Senate Appropriations Subcommittee on Labor-Health and Human Services (HHS)- Education, under the leadership of Chairman Roy Blunt (R-MO) and Ranking Member Patty Murray (D-WA), held a hearing on the FY 2018 budget for the National Institutes of Health. Testifying alongside NIH Director Francis S. Collins, MD, PhD were NCI Acting Director Douglas R. Lowy, MD; NHLBI Director Gary H. Gibbons, MD; NIAID Director Anthony S. Fauci, MD; NIDA Director Nora D. Volkow, MD; NIMH Director Joshua A. Gordon, MD, PhD; and NIA Director Richard J. Hodes, MD.

Chairman Blunt in his opening remarks denounced the Trump Administration’s proposed $7.2 billion cut to the NIH in FY 2018, calling them “unacceptable.” He added that “the cut is one you can rest assured this Committee will not take. I certainly fundamentally disagree with the proposed reduction.” Ranking Member Murray also expressed her strong opposition to the proposed cuts and called on both parties to reject the proposal. Full Committee ranking member Patrick Leahy (D-VT) also highlighted the devastating effect of the proposed cut in his opening statement, saying the proposal would “turn progress upside down.”

In FY 2018, sequestration returns under the Budget Control Act of 2011. Therefore, for Congress to ignore the lower spending caps imposed by the law, it will need to reach a new budget agreement soon.  “Raising the caps,” as it is referred to, becomes very important if the NIH and NCI are to receive the robust funding increases necessary. Ultimately, there will either be a Continuing Resolution (CR) to keep government funded after September 30, or Congress will reach a new bicameral, bipartisan budget deal in the coming months. Given the dwindling number of legislative days between now and September 30, a short-term CR is increasingly likely.

Meanwhile, the House Cancer Caucus has been revitalized under the leadership of new bipartisan co-chairs, Representatives Charlie Dent (R-PA), Brian Higgins (D-NY), Derek Kilmer (D-WA) and Kevin Yoder (R-KS). The four Members of Congress and their staff are committed to a more active caucus, and they kicked off their efforts yesterday with a panel focusing on innovation in cancer research and treatment. In a show of strong bipartisan cooperation, all four co-chairs delivered remarks at the event highlighting their commitment to cancer research and their excitement about a rejuvenated caucus. Three of the four co-chairs (Dent, Kilmer and Yoder) serve on the House Appropriations Committee.

The AACR was proud to have three members of the Science Policy and Government Affairs Committee, Louis M. Weiner, MD; Roy A. Jensen, MD; and Frederick R. Appelbaum, MD; along with AACR member Candace S. Johnson, PhD, participate in this event alongside Bill Hinshaw, Executive Vice President and Head, US at Novartis Oncology; and Ashley Murosky, a non-small cell lung cancer patient and advocate. Panel members shared their expertise and perspectives with more than 100 Hill staffers and members of the community.

Take a minute today to call, email, or tweet your senators and members of Congress and urge them to support robust, sustained, and predictable funding increases for the NIH and NCI. You can also send a Thank You Note to members who voted in favor of a $2 billion increase for the NIH in FY 2017.

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NIH Withdraws Proposal to Limit Amount of Funding Scientists Can Receive      

In May, NIH had announced a policy proposal that would have limited the amount of grants a scientist can receive in an effort to increase the amount of funding available for early-career researchers. After receiving feedback from various stakeholders, NIH will instead create the Next Generation Researchers Initiative.  

The goal of the original proposal was to address a funding imbalance that exists because established Principal Investigators are far more likely to submit successful research grant proposals than early- and mid-career investigators. The idea was that capping the amount of funding one investigator can receive w0uld free up money that would then be available to early- and mid-career researchers. However, after pushback from various stakeholders, NIH scrapped the proposal and instead introduced the Next Generation Researchers Initiative (NGRI).

According to a statement by NIH Director Francis S. Collins, MD, PhD, the Next Generation Researchers Initiative will "free up substantial funds from NIH's base budget, beginning this year with about $210 million, and ramping to approximately $1.1 billion per year after five years to support additional meritorious early-stage investigators, as well as mid-career investigators; track the impact of NIH Institute and Center funding decisions for early- and mid-career investigators with fundable scores to ensure this new strategy is effectively implemented in all areas of research; place greater emphasis on current NIH funding mechanisms aimed at early- and mid-career investigators, with an aim of funding most early-career investigators with applications that score in the top 25th percentile; and encourage multiple approaches to develop and test metrics that can be used to assess the impact of NIH grant support on scientific progress."

The initiative defines early- and mid-career investigators as "those with ≤ 10 years as a principal investigator who are about to lose all NIH funding or are seeking a second award for highly meritorious research."

Lacking from the proposal, however, was any specificity as to where the funds for the initiative would come from, aside from NIH officials stating that a “reprioritization of funds” would take place. Dr. Collins, in his statement, also added that the ramping up of funds for the initiative would be "pending availability of funds."

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Norman (“Ned”) Sharpless, MD, Nominated as Director of the National Cancer Institute     

The AACR congratulates Ned Sharpless, MD, on his nomination by President Donald Trump to serve as the 15th director of the National Cancer Institute (NCI).

“Dr. Sharpless brings impressive qualifications to this extremely important position, including his background as a top-tier physician-scientist and his previous positions at the University of North Carolina (UNC), including his current role as director of the prestigious UNC Lineberger Comprehensive Cancer Center," said AACR President Michael A. Caligiuri, MD, director, The Ohio State University Comprehensive Cancer Center and chief executive officer of the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. "His enthusiasm for innovative scientific methods and ideas, as well as his appreciation for the value and importance of basic research to advancing translational discoveries, will allow the NCI to continue leading the way in programs aimed at preventing disease, improving health and reducing suffering from cancer, while also helping to maintain America’s edge in the life sciences."

Dr. Sharpless will succeed Doug Lowy, MD, who has served as acting director of the NCI since the spring of 2015.  During his two years as acting director, Dr. Lowy provided critical leadership to advance the National Cancer Moonshot Initiative that Vice President Biden spearheaded during the final year of the Obama Administration.

“The entire cancer research and patient care community owes Dr. Lowy a tremendous amount of gratitude over the past two years for his extraordinary dedication and outstanding commitment to reducing cancer incidence, morbidity, and mortality,” said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. “Last night’s appointment by President Trump to select Dr. Sharpless as NCI’s next director ensures a continuity in leadership and management at the NCI that is especially needed during this historic era of unprecedented scientific opportunities that are before us. Therefore, we are absolutely thrilled about Dr. Sharpless’ appointment as we greatly respect and value his expertise and leadership in the cancer research community, and the AACR truly looks forward to working with Dr. Sharpless in the months and years to come.”

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Basket Trials: Accelerating Precision Medicine    

Benjamin Wolfson is a PhD Candidate in Molecular Medicine at the University of Maryland, Baltimore, focusing on the role of noncoding RNAs in the breast cancer microenvironment. Find more of his writing here and follow him on Twitter.

On May 23rd 2017, the cancer research community applauded a landmark accomplishment when for the first time the U.S. Food and Drug Administration (FDA) approved Merck's pembrolizumab for use in tumors located in any tissue. While cancers are traditionally organized and treated based on their tissue of origin, tumor sequencing has demonstrated that there are important genetic and molecular similarities between tumors across tissue types. These data prompted researchers to hypothesize that molecularly targeted therapies could be effective independent of a disease's tissue of origin or histology. This means that drugs that have been approved for one cancer type may be effective in others as well as long as the molecular target is present, leading to exciting new avenues of treatment across all cancers.

In the past, cancer drug approval in different diseases was accomplished by carrying out individual clinical trials for each tumor type. The FDA has approved almost 70 targeted therapeutic agents, many for use in multiple cancers, including trastuzumab (approved in both breast cancer and adenocarcinoma of the stomach) and imatinib (first approved in leukemia and later approved in four additional cancers). However, the traditional clinical trial paradigm is prohibitive to high-throughput drug development; standard clinical trials are designed to test the efficacy of one drug in one disease at a time, a process that can take between 5-10 years per tissue type.

While the same drug can be approved for different diseases through multiple, time consuming, iterations of this process, researchers are designing new, broader, clinical trial paradigms to speed up the approval of drugs in other diseases. One of the most exciting of these new methodologies is the basket trial, which allows clinicians to investigate multiple drugs or diseases under the same clinical trial framework, each in their own "basket." By analyzing a patient's tumor response in the context of their basket, the trial can fluidly evolve to match how patients respond; baskets that do not respond well can be discontinued, while those demonstrating a good drug response can be immediately expanded to test the drug in a larger group. If a drug is shown to be effective regardless of tumor location, it may be approved for use in drug-target containing tumors located in any tissue, even those not included in the basket trial (tissue-agnostic use).

The first cancer drug to garner FDA approval for tissue-agnostic use is pembrolizumab. Pembrolizumab was first approved for treatment of patients with melanoma, and later for use in lung and several other solid tumor cancers, each after an independent traditional clinical trial. To investigate pembrolizumab in additional tissue sites, Merck initiated a basket trial investigating pembrolizumab's efficacy in patients with 15 different cancer types, all expressing pembrolizumab's target, PD-1. Based on the positive results of these trials, the FDA granted pembrolizumab accelerated approval, meaning it will undergo further study but is immediately available to patients whose disease will progress without it. This tissue-agnostic drug approval has been met with tremendous enthusiasm from the cancer research community, and may be the next step toward delivering on the promise of personalized medicine. The advent of next generation sequencing has made it easier, cheaper, and faster to sequence a patient's tumor as a routine test when performing biopsies, and identification of a tumor's exact genetic landscape means that the most important mutations and targets can be identified. This allows doctors to create an individualized treatment regimen according to a patient's tumor-specific mutations, and the approval of drugs for tissue-agnostic use significantly increases the number of drugs available for targeted treatment.

Increased implementation of the basket trial design will benefit patients that are the underserved by classic clinical trials. Often it is difficult to recruit enough participants for clinical trials testing rare mutation-targeting drugs leaving patients with these mutations without effective treatment options. Basket trials can expand the population of patients eligible for a trial, benefiting those with less common diseases. Moreover, trials can be conducted in a shorter time, with fewer patients, and at lower cost than traditional trial designs.

Despite these benefits, basket trials do have disadvantages. First, the presence of a molecular target in a tumor does not guarantee it plays an important role or that inhibition of that target will have a beneficial effect for the patient. This was recently demonstrated with the BRAF inhibitor vemurafenib. While it is highly effective in BRAF mutation-carrying, metastatic, melanoma patients, it is ineffective in colorectal cancer with mutated BRAF. Basket trials also increase the statistical complexity of a clinical trial. Each basket of the trial carries its own chance of resulting in a false positive, which combine to increase the rate of false positives for the trial as a whole. Finally, it's nearly impossible to simplify tumors down to one or two targetable mutations. The biological context of mutations impacts the role that a mutation has in the tumor, and basket trials will only show that a treatment works if the tumor's survival relies on the targeted pathway.

We remain on the cusp of a true paradigm shift in personalized genomics and medicine, and the approval of pembrolizumab for tissue-agnostic use is the first glimpse of this future. Forty three percent of all tumors share more genetic similarities to tumors from different tissues than tumors from their own tissue of origin, and yet we still classify and treat cancers based on their tissue of origin. This is a rudimentary construct for what are incredibly complicated diseases. Basket trials are the first clinical reflection of the need to change this, and will set the foundation for more innovative clinical trial design to fulfill the hopes of personalized cancer treatment.

For more information concerning the approval of pembrolizumab, and to stay up to date with current events in cancer drug development and approval, we recommend the FDA's new podcast: Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)

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New Paper on Oncology Clinical Pathways Highlighted at Turning the Tide Conference    

On Thursday, June 29, thought leaders from across the cancer community gathered in the nation’s capital to explore solutions that foster continued innovation and deliver better outcomes for patients. Co-hosted by the Personalized Medicine Coalition (PMC), the American Association for Cancer Research (AACR), Feinstein Kean Healthcare (FKH), and CancerCare, the third national conference of the Turning the Tide Against Cancer Through Sustained Medical Innovation initiative brought together stakeholders from the scientific, clinical, regulatory, industry, and patient advocacy communities to participate in solutions-oriented discussions that delineate strategies for policymakers to consider that support meaningful patient engagement and deliver value to patients.

The one-day program included interactive panels, spotlight sessions, and a keynote presentation by Joan Lunden, former host of Good Morning America, journalist, author, patient advocate and breast cancer survivor, to discuss value, innovation, and patient access and how these key areas of concern render meaningful patient engagement more necessary in cancer research and delivery of care.

“Regarding the critical issues of clinical decision-making and reimbursement, the Turning the Tide initiative reminds us again that the patient voice must be right front and center in the cancer research and care process,” said Edward Abrahams, PhD, president, PMC. “In order to realize the benefits of personalized medicine — which represents the future of oncology — and address the rising cost of cancer care, patients must be active participants in treatment decision-making.”

Ahead of the fifth anniversary of the Turning the Tide Against Cancer initiative, which first convened in 2012, PMC, the AACR, and FKH convened an expert working group of top leaders in cancer research, health care policy, and patient advocacy to explore the shift from volume to value-based care and how this may affect whether clinical pathways are effectively facilitating patient access to high-quality and high-value care. Results from the expert working group, published this week in the journal Clinical Cancer Research suggest that a lack of accountability exists across the continuum of a pathway, leading to the group’s recommendation that an independent third party serve in an accreditation or oversight capacity for these tools. The manuscript, Clinical Pathways: Recommendations for Putting Patients at the Center of Value-Based Care, places the patient at the forefront of the discussion around cancer care, a necessary concept and central theme of Turning the Tide.

"It is an amazing time in the field of oncology," said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. "Scientific data is being collected, shared, and utilized in more productive ways than ever before, and cancer patients are finding it easier to search for and enroll in a cancer clinical trial than at any time in our nation's history. Discussions during today's conference will help catalyze a new phase of community-wide action to ensure that cancer patients' voices become an even more integral part of the cancer research and care delivery processes."

“We are positioned at a unique convergence in health care, with the influx of scientific innovation, health data, and patient engagement driving a shift to value-based care,” said Marcia Kean, MBA, chairman, Strategic Initiatives, FKH. “It is our collective responsibility to incorporate the patient perspective as we develop new health care delivery models so that we can align patient priorities and preferences with available scientific evidence to drive appropriate treatment decisions.”

At the Turning the Tide Against Cancer 2017 National Conference, experts working in oncology innovation and healthcare policy gathered for a dialogue featuring a full patient panel to open and close the event, and an extensive lineup of speakers dedicated to finding solutions that drive patient-centered care.

“It’s time for patient-centered care to be the standard of care,” said Patricia Goldsmith, chief executive officer, CancerCare. “Progress toward this requires partnerships across industry, policy, and advocacy to catalyze broad community action to ensure that the patient’s voice is an integral part of the cancer research and care system. Through the Turning the Tide Against Cancer 2017 National Conference and in the coming years, we remain committed to fulfilling this goal.”

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Differences and Disparities in Cancer    

This article, written by  William G. Nelson, MD, PhD, editor-in-c​hief of Cancer Today, first appeared on the AACR's official blog, the Cancer Research Catalyst.

Nearly 1.7 million new cancer cases and roughly 600,000 cancer deaths are expected in the United States in 2017. The good news is that this reflects an ongoing 1.5 percent annual decline in cancer death rates, likely having resulted in over 2 million fewer cancer deaths from 1991 to 2014.

The more troubling news is that cancer does not affect all equally.

African-Americans have cancer death rates 15 percent higher than Caucasians. Asian/Pacific Islanders, American Indian/Alaska Natives, and Hispanics have higher risks of cancers attributable to chronic infections. Finally, low-income people disproportionately die from cancer.

Differences among individuals can provide clues to why cancer arises and how it might be better prevented or treated. Inherited genes and environmental exposures both contribute. Genetic and environmental factors interact to generate individual differences in cancer risk. As an example, light-skinned Caucasian-Americans exposed to large amounts of ultraviolet radiation from sunlight are prone to develop melanomas and nonmelanoma skin cancers, while darker-skinned African-Americans develop fewer skin cancers, whether sun-exposed or not. These differences in skin cancer risk can be attributed both to genes controlling skin pigmentation and to environmental exposures to ultraviolet light.

For prostate cancer, differences in incidence and mortality rates among races and ethnic groups are not as easily explained. Prostate cancer death rates for African-American men are almost 2.3 times greater than those for Caucasian-American men. Studies of prostate cancer biology hint that genetic and environment differences may account for some of the discrepancy. But inequities in health care access also are almost certainly at fault.

Disparities in access to and use of high-quality health care reflect injustices that should not be tolerated. Cancer disparities can be rooted in inadequate insurance coverage or inability to pay for care, lack of proximity to health care services, low health literacy, reduced trust in providers and the health care system, provider biases and prejudices, overt discrimination, and poor-quality care.

Resolutely targeting cancer disparities can yield spectacular results. Colorectal cancer death rates historically tend to be higher for African-Americans than Caucasians in the U.S., and disparities are the likely culprit. Confronting the challenge, former Delaware Governor Ruth Ann Minner and the state legislature launched a colorectal cancer screening program in 2002, ultimately allocating funds so that all state residents, including the uninsured, would have access to both screening and treatment. By 2009, colorectal cancer screening rates in Delaware had increased from 57 to 74 percent in people 50 and older. Screening rates were similar in African-Americans and Caucasians, fewer colorectal cancers were diagnosed at advanced stages, and the disparity in colorectal cancer mortality between African-Americans and Caucasians had been nearly eliminated.

The current president of the American Association for Cancer Research (AACR), Michael A. Caligiuri, MD, has made cancer health equity a major priority for his yearlong tenure. The AACR, which publishes Cancer Today, now boasts more than 37,000 members, with expertise spanning all aspects of cancer research and care. It’s the perfect organization to explore the reasons for differences in cancer incidence and mortality rates and to illuminate the disparities in health care that must be overcome.

William G. Nelson, MD, PhD, is the editor-in-chief of Cancer Today, the quarterly magazine for cancer patients, survivors, and caregivers published by the American Association for Cancer Research. Nelson is the Marion I. Knott professor of oncology and director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore. You can read his complete column in the summer 2017 issue of Cancer Today.

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AACR on Capitol Hill: Special Briefing on Progress in Immuno-oncology    

One of the most promising areas of cancer research is the field of immuno-oncology. Scientists are discovering new ways to arm a patient’s immune system so that it can attack cancer cells, and the result has been one of the most transformative approaches to cancer treatment that has ever entered the clinic. For many patients, cancer immunotherapies are already providing lifesaving results where other treatments had failed or were not viable. But realizing more breakthroughs in this area and broadening the scope of cancers that can be treated with immuno-oncology requires a sustained, federal investment in cancer research through the National Institutes of Health and the National Cancer Institute.

The American Association for Cancer Research and the Society for Immunotherapy of Cancer are pleased to host this briefing that will highlight some of the exciting innovations that are being delivered through immuno-oncology, illustrate the hope that these advances are bringing to cancer patients, and note the challenges that still need to be overcome so that even more cancer patients can benefit from these revolutionary treatments.  

Confirmed Speakers:

  • Elizabeth M. Jaffee, MD, AACR president-elect 2017-2018; deputy director, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore
  • Lisa H. Butterfield, PhD, president, SITC; professor of medicine, surgery and immunology; and director, UPCI Immunologic Monitoring and Cellular Products Laboratory, University of Pittsburgh.
  • Steven A. Rosenberg, MD, PhD, chief of surgery, National Cancer Institute, Bethesda, Maryland
  • Bernard A. Fox, PhD, past-president, SITC; chief, Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center
  • Daniel S. Chen, MD, PhD, vice president, global head of cancer immunotherapy development, Genentech
  • Stefanie Joho, colon cancer survivor and patient advocate

Date: July 19, 2017. Time: noon - 1:30 p.m.

Location: Russell Senate Office Building, Room 485

Click here to register today. Lunch will be served.

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FDA-AACR Joint Workshop: Oncology Dose-finding Part III    

Given the recent history of approvals based on the results of early phase trials driven by extraordinary efficacy data, the incentive for conducting rigorous dose-finding trials may not be overtly apparent. However, the increasing need for the development of combination therapy due to resistance to monotherapy and poor tolerance of approved dosing regimens underscores the need for a more efficient process of dose selection in the early stages of study design.

FDA and AACR have successfully held Oncology Dose-finding Workshops in 2015 and 2016. Patient and dose selection of oncology drugs will be of critical importance, as recent approvals of immune checkpoint inhibitors (ICIs) and early, promising readouts from studies combining ICIs with chemotherapy, targeted therapy, and other immuno-oncology agents will put enormous pressures on the current clinical trial infrastructure of the U.S. and the international community. A recent article in The Cancer Letter reported that 803 clinical trials currently testing PD-1 and PD-L1 drugs had over 160,000 slots for adult patients. As more ICIs enter the market, additional trials will seek to combine these products with standard of care therapies, novel small molecules, targeted antibodies, and other biologic therapies such as vaccines and engineered T-cells. This year’s workshop will focus on approaches to combination therapy and best practices regarding patient and dose selection, biomarkers to aid in selection, and novel endpoints that can define patient benefit.

See the draft agenda.

SESSION I:    Immuno-Oncology (IO) Overview – Scope of the problem

SESSION II:    Key Translational and Design Questions for IO Agents

SESSION III:    Considerations for Dose Selection of IO Combination Products

Workshop Co-chairs:

Amy E. McKee, MD

Deputy Director (Acting), Office of Hematology and Oncology, Center for Drug Evaluation and Research, FDA

Elizabeth M. Jaffee, MD

AACR president-elect 2017-2018; The Dana and Albert "Cubby" Broccoli professor of oncology; deputy director, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; co-director, Gastrointestinal Cancer Program The Johns Hopkins University School of Medicine

Date: July 20, 2017. Time: 8 a.m. - 4 p.m.

Location: W. Washington DC Hotel, 515 15th St. NW, Washington, DC 20004

Registration is now available at this link.

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Register Today: Rally for Medical Research   

In May, we were shocked to learn that the Trump administration is proposing to cut $7.2 billion from the National Institutes of Health (NIH) budget in fiscal year (FY) 2018, a nearly 21 percent cut. These draconian proposed cuts make this year’s Rally for Medical Research more important than ever for protecting funding for lifesaving cancer research. The fifth annual Rally for Medical Research Hill Day will be held Sept. 14, 2017, in Washington, D.C., with a reception on the evening prior. Registration is now open and all interested advocates of biomedical research are invited to register.

For those unable to travel to D.C. in person, there will also be a National Day of Action on September 14, where advocates will be able to contact their senators and representative from anywhere in the United States to urge support for the National Institutes of Health. Save the date and sign up here for the National Day of Action. We will then send you a reminder email on September 14.

Stay up-to-date on by visiting the Rally website, Facebook, and Twitter pages.

Interested in becoming a Sponsoring Organization for the 2017 Rally for Medical Research Hill Day? Information is available here!

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