The American Society of Clinical Oncology's year-end report on the major clinical cancer advances in 2013 documents much to celebrate, but sounds a strong note of alarm due to budget cuts for cancer research funding.
To keep cancer research strong and counter funding cutbacks, ASCO is seeking a fiscal year 2014 appropriation of $32 billion for the National Institutes of Health, including $5.2 billion for the National Cancer Institute.
While the recent Senate-House budget agreement is a step in the right direction of making up for what ASCO calls years of stagnant funding and cuts to NIH, the agreement falls short in protecting the nation's cancer care infrastructure, the report says. Specifically, ASCO said, it is “extremely disappointed that the budget conferees did not reverse the cuts to Medicare, including the unintended 30 percent cut to payments for physician-administered drugs under Medicare Part B.”
The comprehensive new report, published as a special article now online ahead of print in the Journal of Clinical Oncology (doi: 10.1200/JCO.2013.53.70762013), cites 76 significant clinical advances, including two funded directly by ASCO's Conquer Cancer Foundation:
* Preclinical research on the mechanisms by which a new targeted therapy, AGI-5198, inhibits the growth of cancerous cells in glioma; and
* A clinical trial showing that cabozantinib, a new kinase inhibitor, results in an antitumor effect and reduction of circulating tumor cells in advanced prostate cancer.
In an introductory message to the report, ASCO President Clifford A. Hudis, MD, Chief of the Breast Cancer Service at Memorial Sloan-Kettering Cancer Center, says: “Both dramatic and subtle breakthroughs occur, so that progress against cancer typically builds over many years. Success requires vision, persistence, and a long-term commitment to supporting cancer research and training.”
In 2011, ASCO released a sweeping report setting forth a new vision for cancer research incorporating the latest findings from molecular biology (OT 12/10/11 issue). That report, Accelerating Progress Against Cancer: ASCO's Blueprint for Transforming Clinical and Translational Research, was specifically timed to come out 40 years after President Nixon signed the National Cancer Act in December 1971, and guides ASCO's mission and planning.
Building on previous research, the selected studies for ASCO's 2013 Clinical Cancer Advances report “revealed remarkable progress on a wide range of cancers, including some cancers for which there had been frustratingly limited success over decades,” said Jyoti D. Patel, MD, Co-Executive Editor of the report.
Patel, Associate Professor in the Division of Hematology/Oncology at the Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center at Northwestern University, co-led—with Bruce J. Roth, MD, Professor of Medicine, Oncology Division, at Washington University in St. Louis—a group of specialty editors who reviewed studies for the report.
As did the American Association for Cancer Research's Cancer Progress Report 2013 (OT 10/25/13 issue), the ASCO report highlights targeted therapies, which NIH Director Francis Collins, MD, PhD, sees as the future of medicine: “For most of medicine's history we've been doing one-size-fits-all because it's the best we could do,” commented Collins in a multimedia forum called Engaging Innovation! (http://bit.ly/1eb6FRQ) sponsored by Friends of Cancer Research.
“But now the revelations about individual differences are making it possible to think about a much more personalized approach. “The leading edge of this is cancer. We are learning that every cancer has a different set of drivers causing that good cell to grow when it should have stopped, and that set of drivers is predictive about how that cancer will respond to therapy.”
The ASCO report notes that between October 2012 and October 2013 the Food and Drug Administration expanded the indications for six existing anti-cancer therapies and approved nine new anti-cancer drugs. The following are some of the wide-ranging clinical cancer advances cited in the report.
* Progress in molecular mapping of cancers. In 2013, The Cancer Genome Atlas (TCGA) research network, launched by NCI in 2009, reported the results of comprehensive molecular analyses of kidney and endometrial cancers, along with acute myeloid leukemia (AML). TCGA researchers are mapping genomic changes in more than 20 different cancer types; their findings are in the research domain worldwide, which hopefully will lead to new, targeted therapies.
* Circulating tumor DNA as a potential new marker of treatment response in metastatic breast cancer. Researchers knew that elevated levels of circulating tumor cells (CTCs) signal a worse response to therapy for women with advanced breast cancer. But the only FDA test for CTCs is often not sensitive enough to detect tumor burden. This year a proof-of-concept study showed that circulating tumor DNA (fragments of cell-free DNA that the primary tumor sheds into the bloodstream) was more sensitive for detecting tumor response to therapy than CTCs or the biomarker CA 15-3 are.
* Progress in immunotherapy. The ASCO report cites early studies confirming that the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway plays a key role in the immune response to some cancers. Targeted drugs that block the PD-1 protein on immune cells or the PD-L1 protein on cancer cells caused quick and long-lasting tumor shrinkage in patients with advanced melanoma.
Additionally, the report cites the efficacy of engineered T cells in aggressive, chemotherapy-resistant acute lymphoblastic leukemia (ALL). With a new immunotherapy technique, chimeric antigen receptor-modified T cells, the patient's immune cells are collected, genetically engineered in the laboratory, grown in large numbers, and infused back into the patient. (AACR's 2013 report also hailed progress in immunotherapy, and included a special section on it.)
* Value of longer-term tamoxifen therapy. New research shows that taking tamoxifen for 10 years instead of the currently recommended five years substantially reduces the risks of breast cancer recurrence and death following surgery in carefully selected women with estrogen receptor-positive, early-stage breast cancer.
* Identification of the cause of treatment resistance in some colorectal cancer patients. New studies show that having extra copies of the gene MET may be linked to resistance to epidermal growth factor receptor (EGFR) targeted treatment in some colorectal cancer patients without mutations in the KRAS gene. This discovery may lead to new therapeutic approaches for these patients.
* Promise of a new oral drug for patients with treatment-resistant chronic lymphocytic leukemia (CLL) or mantle cell lymphoma. Ibrutinib targets and blocks the enzyme Bruton's tyrosine kinase. Two studies suggested that this new drug appears to be not only effective but also lower in toxicity. (Ibrutinib was recently approved by the FDA for patients with treatment-resistant mantle cell lymphoma or recurrence.)
* New gene abnormality detected in multiple cancers. New research shows that many different cancerous tumor types harbor novel abnormalities termed fibroblast growth factor receptor (FGFR) gene fusions. Among the cancer types harboring these gene fusions are breast, prostate, thyroid, bladder, oral, head and neck, and lung. At least some of these patients may benefit from the investigational agent PD173074 and pazopanib, both of which target FGFR.
* Value of daily multivitamins for older men. Data from the Physicians Health Study II show that daily multivitamins provide a small but statistically significant reduction in total cancer risk for men age 50 and older.
* Value of low-dose CT screening for lung cancer in heavy smokers. Data from the NCI-sponsored National Lung Screening Trial (NLST) showed that annual screening with low-dose helical computed tomography, also referred to as spiral CT, leads to a 20 percent reduction in lung cancer mortality relative to screening with chest x-ray examination. NLST includes some 53,000 participants (symptomless upon entry) ages 55 to 74 who are current and heavy smokers, defined as the equivalent of smoking a pack of cigarettes a day for 30 years.
In its new report, ASCO tempers the good news about 2013 clinical cancer advances with bleak facts about flat funding for cancer research over the last 10 years. Including cuts from sequestration, ASCO calculates that the NIH budget has declined by more than 22 percent ($6.1 billion) over the last decade, after adjusting for inflation.
As specific examples of harm from budget cuts, the report cites the expected enrollment of 750 fewer new patients in 2013 enrolled in all NIH clinical trials at the NIH Clinical Center hospital; the Mayo Clinic, which lost $23 million in federal research funding because of the sequester in fiscal year 2013; and the Moffitt Cancer Center, which saw its budget reduced by $1.7 million because of the sequester. At Moffitt, a large project studying lung cancer was not renewed and had to be curtailed.
In his Engaging Innovation! talk, the NIH Director noted that he had sent a tweet in May asking for comments about how the sequester was personally affecting people. The results, from more than 2,000 replies, were “heartbreaking in many instances,” he said, with stories about rescinded laboratory positions, investigators having to shrink clinical trials, and people wondering whether to pursue scientific careers at all, or whether to move to another country to pursue their career goals.
But, Collins said he remains optimistic. “The science that we have the opportunity to do now is breathtaking,” he said. “We'll get there, so people shouldn't be too anxious about the current stress on the system. I can't imagine that this will go on indefinitely.”