Tivozinab Upcoming Approval! Immunotherapy Side Effects. Novel Method to Block Immunosuppression! Ipi/Nivo Yields Longer Treatment Free Survival !
Progress and challenges in biomarkers for kidney cancer biomarkers a video from Hans Hammers at ESMO.
This is an excellent article by doctors at Fox Chase Cancer Center in Philadelphia. The original article can be found in Clinical Advances in Hematology & Oncology, Vol. 16, Issue 10, October, 2018. Please feel free to share this with your doctor or caregiver.
I am excited to announce our newsletter, which enables us to provide patients, survivors, and families with the latest news in kidney cancer research and treatment. Please take a look at the latest issue below and don’t forget to subscribe!
On September 28th, the President signed into law the Defense, Labor HHS spending package. Included within this historic bill is the Defense Health Program that has increased the funding for the Kidney Cancer Research Program pursuant to the CDMRP from $15 million to $20 million annually. KCAN led the charge for the increase to this important program.
Last week, the Senate passed by a vote of 93-7 an appropriations ('spending') conference bill package that was agreed to by both chambers to fund the Pentagon and the Departments of Labor, Health & Human Services and Education.
Today, the House passed an identical bill by a vote of 361-61. This was the second of three funding bills to pass both chambers. This bill now goes to the President for signature, veto or pocket veto.
The total price tag is an $854 billion spending bill that helps avoid a government shutdown This is more than 70% of our discretionary spending and is a big deal. It is the first time in over 15 years that the bills were passed on time, (according to 'Regular Order'). The bill now goes to the President's desk for signature (possibly tomorrow) and he has signaled he is willing to sign it into law.
This is great for the kidney cancer community for two reasons.
Deep within the Defense Department portion of the bill is the Defense Health Program which funds various medical research initiatives including kidney cancer.
Through the efforts of many of us, the inaugural Kidney Cancer Research Program was signed into law last year with a funding level of $10 million. Advocacy efforts and countless DC visits over the past year resulted in a $5 million annual increase for FY'18 and just today another $5 million annual increase to $20 Million for FY'19.
Today's package included appropriations, which fully funded, Labor, Health and Human Services (HHS) and Education for fiscal 2019. The bill included a $2 Billion increase for the NIH (and a significant increase for the National Cancer Institute) and showcases Congress’s ongoing commitment to medical research in which funding advances science, innovation, and economic growth.
It is important to highlight several of the Congressional champions in the House. In particular, House Appropriations Committee leadership, including Chairman Rodney Frelinghuysen (R-N.J.), Ranking Member Nita Lowey (D-N.Y.), Subcommittee Chair Tom Cole (R-Okla.), and Ranking Member Rosa DeLauro (D-Ct.), for their longstanding support for the CDMRP program, including the KCRP and for increased funding for the NIH and the National Cancer Institute.
In the Senate, Senator's Shelby, Blunt, Durbin and Murray were instrumental in getting this legislation passed.
If you live in any of these representatives districts, please contact their offices and thank them for their support for medical research and for providing hope to the kidney cancer community.
Medical Research Funding: Kidney Cancer Research & NIH gets Boost in Funding by “Mini-bus” Passed by Senate
On September 18, the Senate passed the FY19 spending package that covers Defense, Labor, Health and Human Services and Education Departments as well as a continuing resolution for the remaining programs until December 7 to avert any partial shutdown. The appropriations package was carried by a vote of 93 – 7, with the dissenting votes coming from Sens. Jeff Flake (R-AZ), Mike Lee (R-UT), Rand Paul (R-KY), David Perdue (R-GA), Ben Sasse (R-NE), Pat Toomey (R-PA), and Bernie Sanders (I-VT). The House is slated to vote on the measure next week (before the end of the fiscal year on September 30). The Labor-HHS-Education division of the bill provides $178.1 billion in discretionary funding for the Departments of Labor, Health and Human Services, and Education and Related Agencies to continue investments in critical medical research, opioid abuse prevention and treatment, and education. The bill includes $39.1 billion for the National Institutes of Health (NIH), an increase of $2 billion over current funding, and $3.8 billion to combat the opioid crisis, an increase of $206 million over current funding. The bill also includes an increase to $20 million for the KCRP (Kidney Cancer Research Program) pursuant to the CDMRP (Congressionally Directed Medical Research Program). This increase came about through the combined efforts of a number of advocacy groups coordinated under the leadership of KCAN.
White Plains, NY, Sept. 4, 2018--Bryan Lewis, president, Kidney Cancer Action Network, met with Congresswoman Nita Lowey at her White Plains District Office on Aug. 30, 2018. The purpose of the meeting was to both thank Congresswoman Lowey for her instrumental support in helping to secure $15 million annually in research funding for kidney cancer and review the resulting impact. This past year, an inaugural $10 million program was launched that has awarded 22 meritorious research applicants with crucial funding for this disease. The research community has been reinvigorated and this infusion of research dollars has motivated and drawn a new wave of young researchers to the field. This, in turn, has created a renewed sense of hope for a cure in the patient community throughout Westchester County and beyond.
Statement by the Defense Health Research Consortium
On the Passing of Senator John McCain
The Defense Health Research Consortium (DHRC) pays tribute to the exemplary career
of Senator John McCain (R-AZ), and his devotion to his family, his country, and the men
and women who serve our country in the U.S. Armed Forces. Senator McCain was the
embodiment of courage, tenacity, passion and service, and he will be greatly missed in
the U.S. Senate.
Senator McCain challenged us to do a better job explaining to Congress and the
American public the importance of DoD medical research to the warfighter, veterans,
military families and national security. The DHRC also appreciated his boundless
energy and determination in ensuring that the Defense Appropriations Act, which funds
the defense health research programs, was enacted into law every year.
The Consortium and its 39 member organizations will greatly miss Senator John
McCain, and we send our deepest condolences to his family and friends who are
grieving his loss.
WASHINGTON — The Senate on Thursday approved a massive spending bill that would direct more than $670 billion to the Defense Department for the 2019 fiscal year.
The defense spending legislation is part of a larger labor, health and human services and education spending bill, an unusual combination, a lawmaker noted. The measure, which was part of a larger funding package of more than $850 billion that also included an increase in funding for the NIH and NCI, will fund priorities directed in the recently passed 2019 National Defense Authorization Act, which directs policy and spending plans for the Defense Department.
The Senate voted 85 to 7 to pass the legislation, with some lawmakers absent, including Sen. John McCain, R-Ariz., chairman of the Senate Armed Services Committee, who is battling brain cancer.
The legislation, H.R. 6157, now goes to a conference committee made up of members from both the House and Senate and has to be reconciled with its House version before requiring votes in both chambers. If approved, the legislation goes to the president for his signature.
“The funds meet many of the requirements of our military commanders, equipping and training units to meet and overcome the most dangerous of emerging global threats,” Senate Majority Leader Mitch McConnell, R-Ky., said ahead of Thursday’s vote. “As ever, our obligation to this all-volunteer force is to provide adequate training, weaponry and skills so that Americans always prevail on the battlefield.” In June, the House passed its defense appropriations measure, H.R. 6157, in a vote of 359 to 49, followed by today’s Senate passage.
The defense budget moves on two tracks: the annual NDAA sets policy changes and expenditures for the military and determines how the money will be spent, while the defense appropriations bill is what actually moves money to the Pentagon to support the plan.
“It probably sounds like a pretty unusual combination even though I think most voters, most taxpayers understand that to get this work done in the time frame we have to do it, we generally need to bring more than one topic together on the floor at the same time,” Sen. Roy Blunt, R-Mo., said Thursday of the combination of efforts being funded by the same appropriations bill, adding it could be on Trump’s desk by the start of the fiscal year Oct. 1.
The so-called “minibus” appropriations bill saw more than two days of debate on the Senate floor this week.
At this pace, it’s possible the defense spending bill could see passage by Oct. 1, which would mark the first on-time passage of the NDAA and its funding companion bill in more than 20 years.
However, lawmakers are on a tight clock. The House is on recess until Sept. 4, and Republican lawmakers are racing to confirm Supreme Court nominee Judge Brett Kavanaugh ahead of the midterms. Congress is also facing an array of challenges from the Trump White House that could derail their work.
For example, Trump has threatened not to sign off on government spending plans if there isn’t sufficient money to build a wall along the U.S.-Mexico border. This, as Trump is facing questions tied to the investigation into Russian interference in the 2016 presidential election and a growing list of former administration aides facing criminal charges, which could divert attention on Capitol Hill from finishing up its NDAA funding measure on time.
Without a spending measure in place by Oct. 1, lawmakers might need to pass a temporary budget measure, which is known as a continuing resolution, to keep the government operating.
Thanks to the American Cancer Society - Cancer Action Network for this effort.
On July 23 the U.S. House of Representatives unanimously approved the Palliative Care and Hospice Education and Training Act (PCHETA). The bipartisan bill would increase federal research funding for palliative care, including symptom and pain management, and would establish palliative care education and training programs for doctors, nurses and other health professionals. It would also create a national public education and awareness campaign to educate patients and providers about the availability and benefits of palliative care. The bill’s passage in the House of Representatives clears the way for Senate consideration.
ACS CAN President Chris Hansen released the following statement on the bill:
“Cancer patients, survivors and others living with serious illnesses and chronic pain have reason to celebrate today as a result of the House of Representatives’ approval of PCHETA on a bipartisan basis. The PCHETA legislation, which ACS CAN and the Patient Quality of Life Coalition (PQLC) have long advocated for, will improve the coordination of care and quality of life for cancer patients, survivors and others living with serious illnesses. There is a critical need to expand patient awareness of, and access to, palliative care services and appropriate pain management. We believe the PCHETA legislation will greatly aid in this effort through updating pain and symptom management training for health care providers and also bolstering federal pain research efforts at the National Institutes of Health.
“We commend Congressmen Elliot Engel (D-NY), Tom Reed (R-NY) and Buddy Carter (R-GA) for championing the PCHETA legislation and thank House Energy and Commerce Committee Chairman Greg Walden (R-OR) and Ranking Member Frank Pallone (D-NJ) for their leadership. We now urge the Senate to quickly follow suit and pass this legislation in a bipartisan fashion.”
University of North Carolina Lineberger Comprehensive Cancer Center scientists have uncovered a potential therapeutic target for kidney cancers that have a common genetic change. Scientists have known this genetic change can lead to an overabundance of blood vessels, which help feed nutrients to the tumors. Their latest finding shows a potential new cancer-driving pathway.
More than 90 percent of the most common type of kidney cancer have a genetic change that leads to the loss of an important tumor suppressor gene called VHL. In a study published in the journal Science, researchers identified a new downstream effect of this genetic change that is helping to drive kidney cancer: They found that a protein called ZHX2 over-accumulates in these cells and helps to turn on other signals involved in cancerous growth. Their findings suggest that ZHX2 is a potential new therapeutic target for clear cell renal cell carcinoma, which is the most common type of kidney cancer.
"If you lose VHL, you will accumulate lots of this ZHX2 protein, which will turn on signals that promote kidney cancer," said UNC Lineberger's Qing Zhang, PhD, an assistant professor in the UNC School of Medicine Department of Pathology & Laboratory Medicine and Pharmacology. "This protein could be a potential therapeutic target used to treat kidney cancer on its own or in combination. The next step is to try to figure out how we can target it therapeutically."
Renal cell clear cell carcinoma is the most common type of kidney cancer, accounting for about 70 percent of all cases, researchers report. Approximately 90 percent of patients with clear cell renal cell carcinoma have genetic mutations or alterations that cause them to lose the function of VHL. When the function of VHL is gone, cells can accumulate signals that trigger blood vessels to grow.
"VHL is the most important tumor suppressor in clear cell renal cell carcinoma," Zhang said. "There are extensive reports showing that from initiation to tumor progression to metastasis -- during the whole process of kidney cancer development -- VHL plays a central role. It is important to understand how the VHL loss contributes to kidney cancer, and how we can therapeutically target the downstream effects of this loss in kidney cancer."
There are U.S. Food and Drug Administration-approved drugs that block cell signals involved in abnormal blood vessel production -- which is a downstream effect of VHL loss -- that are part of the standard of care for clear cell renal cell carcinoma. Patients can show little response to these drugs or can develop resistance, so Zhang and his colleagues wanted to search for other targets that accumulate in cells lacking VHL function that help to drive the abnormal cancerous growth.
"We wanted to understand, once VHL is lost, what else in kidney cancer cells is promoting oncogenesis?" Zhang said. "Therapeutically speaking, we're trying to understand how we can target these novel signaling pathways, once we identify them."
The researchers created a screening technique to discover new molecules that might help drive cancer when VHL is lost. This led them to determine that kidney cancer cells lacking VHL usually had more ZHX2. By eliminating ZHX2 from their laboratory models, they inhibited cancer cell growth, invasion and the cancer's spread. In addition, they saw that it was involved with signals that can help cancer cells grow.
UNC Lineberger's William Kim, MD, said there have been major advances in the treatment of kidney cancer with the development of molecularly-targeted therapies and immune-based treatments. However, additional treatments are needed to reach more patients with metastatic disease.
"The vast majority of kidney cancers have mutations in VHL, so it makes it a very important gene to investigate," said Kim, who is an associate professor of medicine and genetics in the UNC School of Medicine. "In the last decade or more, we've had quite a number of major treatment advances in kidney cancer. There are nearly a dozen FDA-approved treatments now for this disease, but many of them are similar. Studies like this are important because they delineate the underlying biology of kidney cancer and identify novel, distinct pathways to develop drugs against."
In addition to Zhang and Kim, the other authors are Jing Zhang, Tao Wu, Jeremy Simon, Mamoru Takada, Ryoichi Saito, Cheng Fan, Xian-De Liu, Eric Jonasch, Ling Xie, Xian Chen, Xiaosai Yao, Bin Tean Teh, Patrick Tan, Xingnan Zheng, Mingjie Li, Cortney Lawrence, Jie Fan, Jiang Geng, Xijuan Liu, Lianxin Hu, Jun Wang, Chengheng Liao, Kai Hong, Giada Zurlo, Joel S. Parker, J. Todd Auman, Charles M. Perou, W. Kimryn Rathmell, Marc W. Kirschner, William G. Kaelin Jr., and Albert S. Baldwin.
The study was supported by a U.S. Department of Defense Career Development Award, the University Cancer Research Fund, and the National Cancer Institute. Individual researchers were supported by the V Foundation for Cancer Research, Kimmel Scholar award, Susan G. Komen, the Mary Kay Foundation, the U.S. Department of Defense, the Howard Hughes Medical Institute, the NCI, the National Medical Research Council, and the Biomedical Research Council.
Here is the text of an email letter received from Sen. Bob Casey (D-PA) regarding the Congressionally Directed Medical Research Program.
Dear Mr. Lewis:
Thank you for taking the time to contact me about federal funding for medical research, specifically the Congressionally Directed Medical Research Program at the Department of Defense. I appreciate hearing from you about this issue.
The Congressionally Directed Medical Research Program (CDMRP) at the Department of Defense (DOD) conducts vital medical research that is essential to developing preventive measures, treatments and cures for common and rare diseases. The CDMRP plays a unique role in the medical research community, investing in high-risk, high-reward research through an interactive peer and patient review system. The research is both innovative and successful.
Grants from the CDMRP have been used to support research into diseases as common as Amyotrophic Lateral Sclerosis, also known as Lou Gehrig’s disease, to rarer ones like scleroderma, which affects connective tissue. Fully funding and supporting this program is critical to finding cures and assisting those who suffer from these illnesses, as well as ensuring the United States continues to lead the world in cutting edge, bio-medical research.
Unfortunately, despite the CDMRP’s record of success, there have been regular attempts to end or significantly modify the program. Most recently, H.R. 2810, the National Defense Authorization Act (NDAA) for Fiscal Year (FY) 2018, contained a provision that would limit CDMRP funding to research that meets an extremely narrow set of criteria. I opposed this provision and cosponsored an amendment introduced by Senators Dick Durban of Illinois and Roy Blunt of Missouri to remove it. Although we were unable to remove this provision from H.R. 2810 before it passed the Senate, it was later removed when a compromise version was worked out between the House and the Senate. As a result, the final version of the NDAA did not contain this provision when it was passed by Congress and sent to the President.
Each year as Congress begins its appropriations process, I join my colleagues in signing letters to the Appropriations Committee in support of federal funding for medical research into specific diseases at the Department of Defense. Most recently, I authored a letter to the Senate Committee on Appropriations requesting funding for all of the medical research programs through the CDMRP for FY2019; this letter was signed by 38 other Senators. The CDMRP is a valuable asset to the Department of Defense and the Nation, and it is critical to continue funding this program.
Improving and ensuring health care for all Americans is one of my top priorities in the Senate. As the FY 2019 appropriations process continues, please know that I will continue to fight for federal funding for medical research and prevention efforts as part of that goal.
Again, thank you for sharing your thoughts with me. Please do not hesitate to contact me in the future about this or any other matter of importance to you.
For more information on this or other issues, I encourage you to visit my website, http://casey.senate.gov. I hope you will find this online office a comprehensive resource to stay up-to-date on my work in Washington, request assistance from my office or share with me your thoughts on the issues that matter most to you and to Pennsylvania.
United States Senator
Source: July 10, 2018 – 2:33 p.m. By Jennifer Shutt, CQ
The Senate may turn to its next appropriations package the week of July 23, according to Senate Appropriations Chairman Richard C. Shelby.
“We're working toward bringing some more bills to the floor,” the Alabama Republican said Tuesday. “We don't know exactly yet, but we're hoping it's going to be a number of bills.”
Shelby hinted that the fiscal 2019 Defense appropriations bill (S 3159) will likely be part of that package.
“I am hoping it will be on the floor before [the end of] July,” Shelby said, cautioning that leaders haven’t made a final decision about floor time or what additional spending bills will be added to the Defense spending bill.
Shelby as well as several other appropriators have been advocating for the Labor-HHS-Education spending bill (S 3158) to be added to the Defense bill. And while Senate Majority Leader Mitch McConnell, R-Ky., hasn’t made a final decision, Shelby said the two have had good conversations about the possibility.
“I would like to see us rope Defense and HHS together,” he said.
Sen. Richard J. Durbin, the top Democrat on the Defense subcommittee, is also advocating for the Defense and Labor-HHS-Education bills to be packaged. "[It] makes sense to me to do that," he said.
House Appropriations Labor-HHS (Health & Human Services) Markup – July 11
The House Appropriations Committee is scheduled to mark up the Labor, Health and Human Services, Education, and Related Agencies (L-HHS) bill today. This follows a June 15 markup of the draft fiscal year (FY) 2019 spending bill in the L-HHS Subcommittee. The measure provides a total of $38.3 billion for NIH, an increase of $1.25 billion above the fiscal year 2018 enacted level and $4.1 billion above the President's budget request. The draft bill was passed out of subcommittee by voice vote, with Democratic opposition.
Senate Appropriations Committee Passes FY 2019 Spending Bill
The Senate Appropriations Committee June 28 approved its Fiscal Year (FY) 2019 Labor-HHS-Education spending bill (S. 3158, S.Rept. 115-289), approved by the subcommittee two days earlier. The bill provides a program level of $39.1 billion for the NIH, a $2 billion (5.4 %) increase over the comparable FY 2018 funding level. The committee report estimates that the funding level in the bill would support over 11,400 new and competing grants in FY 2019. Under the Senate bill, all institutes and centers would receive at least a 3.2 percent increase over the FY 2018 funding levels. Special recognition and appreciation to Chair Roy Blunt (R-Mo.) and Ranking Member Patty Murray (D-Wash.) for their bipartisan efforts on the bill.
(Source: Ad Hoc Group for Medical Research)
On Thursday, June 28th, there was concurrent House and Senate action on the FY19 Defense Appropriations Act.
Here is where we stand in the Federal funding (appropriations) process:
HOUSE: The full House approved their version of the Defense Appropriations Act.
SENATE: The full Senate Committee on Appropriations marked up and approved their version of the Defense Appropriations Act.
NEXT STEPS: With this markup (final amendment process) of both Defense and Labor-HHS (Health & Human Services) Appropriations, the Senate Committee on Appropriations has now cleared each of its FY19 bills.
However, the big question is "How many of these bills will be brought to the Senate floor in the coming weeks?."
Democrats will likely insist that the “domestic” appropriations bills first be approved before the Defense bill can come up. The Senate majority is consider packaging the Defense and Labor-HHS bills together. This could mean that we won’t even see the Senate bill on the floor until after the November elections. Stay tuned for more news over the next few weeks.
The good news for kidney cancer community is the FY'19 Defense bill has an increase of $5 Million annually for kidney cancer research to a total of $20 Million. KCAN will keep you updated as this important piece of legislation moves forward.
Note: The following summary was prepared for the benefit of patient organisations who focus on kidney cancer. While this summary has been medically reviewed, the information contained herein is based upon public data shared at this meeting and is not intended to be exhaustive. Patients should ask their physician about any information that pertains to their care.
The American Society of Clinical Oncology (ASCO) Conference in Chicago June 1-5 2018 brought together oncology professionals, patient advocates, and organisations from around the world. For kidney cancer specifically, the conference included the presentation of results from one large blockbuster surgical trial, and several smaller studies in kidney cancer that may influence practice. Here are four studies that were of particular interest.
1. Treatment with axitinib after IO (Immune Oncology)
Dr. Moshe Ornstein and colleagues presented a 40 patient study (abstract 4517) showing that axitinib (Inlyta™) given after IO (immune oncology) therapy was associated with a 9.2 month progression free survival, i.e, the time it for the cancer to start growing again, with good tolerability due to a new way to modify dose in response to toxicity. Side effect rates were reasonably low, with no grade 4 (severe) toxicities. This study shows that you can get fairly good results with axitinib after IO therapy. What we don’t know is whether this drug is superior or equivalent to cabozantinib in this setting, and whether axitinib is capable of potentiating (making more powerful) the immune system.
2. Treatment with pembrolizumab as 1st Line Therapy
Dr. David McDermott presented data from Keynote 427 (abstract 4500) a 107 patient study testing whether pembrolizumab (Keytruda™) given alone to patients who had not received any prior therapy showed effectiveness. Indeed, pembrolizumab in that setting showed that 42 percent of patients had tumour shrinkage of at least 30 percent, and the treatment was well tolerated with a relatively good side effect profile, with fairly low steroid use. On the flip side, approximately 30 percent of patients had their tumours continue to grow while on pembrolizumab, with no benefit. Pembrolizumab, especially given alone, is still investigational as we don’t know how it stands up to currently established standards of care. However, this study shows us that it may be possible in the future to start with one IO drug, and then layer another drug on if no initial benefit is shown. This strategy could decrease toxicity.
3. Cyto-reductive Nephrectomy and sunitinib in Metastatic Kidney Cancer
Dr. Arnaud Mejean presented data on CARMENA (LBA3), a much-awaited study asking the question of whether we should perform surgical removal (cytoreductive nephrectomy) of the primary kidney cancer in patients prior to starting anticancer therapy. This 450 patient study randomly allocated patients to either undergo surgery upfront followed by sunitinib (Sutent™) treatment, or sunitinib treatment alone. There was no statistical difference in outcomes between the two treatment arms, and in fact the trend was toward better outcomes in the non-surgically treated patients. This study shows that performing surgical removal of the primary kidney tumor in every patient with newly diagnosed metastatic kidney cancer is not a wise choice for many, and we need to take a more nuanced approach. A practical alternative is to start with a few rounds of treatment and perform this surgery in individuals where disease shrinkage or overall control is being achieved. Bear in mind that in many countries, sunitinib is a drug that is no longer first choice in this patient population, so the findings are a bit out of date.
4. Cyto-reductive Nephrectomy with IO Therapy
Dr. Jianjun Gao showed how we can integrate cytoreductive nephrectomy along with IO therapy in abstract 4520. In this study patients were treated with upfront IO therapy, which was either nivolumab, nivolumab plus bevacizumab, a blood vessel starving or antiangiogenic agent, or nivolumab plus ipilimumab, another IO agent. In the subgroup of patients who had their primary kidney tumors in place, the choice to remove the tumor was made on a case-by case basis by the Urologist and Medical Oncologist treating the patient. Excellent tumour shrinkage was seen, with over 30 percent response rate, which, when including the surgical removal, was even higher. Although this was a relatively small, 105 patient study, the findings support the concept of starting treatment and then deciding later whether consolidative surgery is appropriate in people who are receiving IO therapies.
Thank you to the kidney cancer patients worldwide who took part in the studies presented at ASCO 2018. We are deeply grateful to each patient and their families for this tremendous contribution.
We look forward to more research news to be published at the European Society of Medical Oncology (ESMO) in October 2018. Many clinical trials are currently ongoing and will contribute to improvements in how we diagnose and select appropriate treatments for each individual diagnosed with kidney cancer.
For more information about ongoing clinical trials for kidney cancer around the world, please see: IKCC Clinical Trials Search.