The American Society of Clinical Oncology's most recent annual report on progress against cancer, the organization's eighth, includes 17 major clinical advances from cancer clinical trials, many of which are targeted treatments based on study results that show an increased understanding of molecular biology.
While the news is good for cancer patients and their physicians, it comes at a time of grave concerns about funding for cancer research as Congress wrestles with an escalating federal deficit.
The good news of the 2012 report includes the fact that between October 2011 and October 2012, the U.S. Food and Drug Administration approved seven new anti-cancer therapies (see box), almost all of which are targeted agents. The FDA also expanded indications for five existing, approved drugs: imatinib mesylate; pazopanib; cetuximab; everolimus; and vincristine sulfate liposome injection.
The 21-member editorial board of Clinical Cancer Advances 2012: ASCO's Annual Report on Progress Against Cancer selected the 17 advances from 87 studies featured, all of which “reflect the payoff of cancer research,” according to an accompanying comment from the report's Co-executive Editor, Bruce J. Roth, MD, Professor in the Department of Medicine, Oncology Division, of Washington University School of Medicine in St. Louis.
“ASCO's report distills the most significant of these advances that are impacting the lives of cancer patients today,” he said. Of these 17 research advances, the editorial board highlighted these top five:
- Adding the mammalian target of rapamycin (mTOR) inhibitor everolimus to the aromatase inhibitor exemestane to slow the progression of advanced hormone-receptor-positive breast cancer in postmenopausal women whose disease progressed despite aromatase inhibitor therapy.
- Using the combination antibody TDM-1 to deliver anti-cancer therapy to human epidermal growth factor receptor 2 (HER-2)-positive breast cancer cells. TDM-1 is a combination of the targeted drug trastuzumab and the chemotherapy drug emtansine.
- Improving the survival of patients with esophageal cancer by delivering preoperative chemotherapy and radiation.
- Reducing colorectal cancer incidence and death rates by screening with flexible sigmoidoscopy, although the new report cautions that “more research is needed to determine how its performance compares with that of colonoscopy.”
- Using the new targeted treatment enzalutamide to extend survival for patients with advanced prostate cancer, which the ASCO report states should become the new standard treatment option for men with chemotherapy-treated advanced prostate cancer.
ASCO President Sandra M. Swain, MD, Medical Director of the Washington Cancer Institute at Washington Hospital Center in Washington, DC, said in her introductory message that she hopes readers of the report will share her “unabashed enthusiasm—and pride—in how far we have come.”
The report shows how research is leading to dramatic improvements in mortality and quality of life for cancer patients, she said, warning, though, that “progress is only part of the story. Cancer remains a challenge, with many cancers undetected until their latest stages and others resisting most attempts at treatment.”
In addition, she said, “The federally funded cancer research system is currently under threat by larger federal budget concerns. Clearly, Congress faces a complex budget environment, but now is not the time to retreat from our nation's commitment to conquering a disease that affects nearly all of us. Bold action must be taken to ensure that we can take full advantage of today's scientific and technologic opportunities.”
ASCO has urged Congress not to institute harmful cuts in cancer research funding. Swain noted that last year ASCO released its Blueprint for Transforming Clinical and Translational Cancer Research plan that sets forth a vision and specific recommendations for making cancer research more targeted, more efficient, and more effective (OT 12/10/11). That plan advocates a new approach to cancer therapeutic development that identifies and ranks molecular targets by priority according to their ability to prolong survival in cancer patients.
On Feb. 11–12, ASCO will host a workshop with the Institute of Medicine on continuing efforts to reorganize, improve, and streamline the clinical trials c ooperative group system run by the National Cancer Institute, a system central to ensuring continuing progress against cancer, she noted. From 1995 to 2010, Richard L. Schilsky, MD, ASCO's newly named Chief Medical Officer (OT, 12/25/12), saw that NCI system from the inside, serving as chair of the Cancer and Leukemia Group B national cooperative clinical research group.
The 2012 ASCO report contains two new sections, on tumor biology and quality cancer care. Also included is a section on “ASCO in Action”, which highlights the year's most important cancer policy developments and issues (including U.S. cancer drug shortages), cancer care guidelines, ASCO's initiative to build a rapid learning system for oncology (CancerLinQ—OT 8/25/12), and its recommendations for improving the quality of care through its Choosing Wisely campaign (OT, 6/25/12).
The report specifically addresses ways of overcoming treatment resistance, noting that cancerous tumors routinely acquire genomic changes, some of which allow them to evade or counter a given anti-cancer therapy. Indeed, the ASCO report cites a study showing that there are genetic variations within a single tumor and variations in the primary tumor and distant metastases within the same patient. “Researchers now know that even subtle genetic differences can make one tumor responsive and another resistant to the same drug,” the report states.
One strategy cited to overcome treatment resistance is to attack more than one target in a molecular pathway that has been found to be critical for a cancerous tumor's survival and growth. Multi-targeted drugs are one way for this strategy to work. As examples of multi-targeted anti-cancer drugs, the report cites:
- regorafenib, which treats patients with treatment-resistant GI stromal tumors (GISTs) and metastatic colorectal cancer;
- crizotinib, which has shown promising activity against aggressive forms of neuroblastoma and anaplastic large-cell lymphoma (ALCL) in children; and
- cabozantinib, which appears to slow the progression of persistent medullary thyroid carcinoma.
A second approach to treatment resistance is to treat cancer patients with two or more agents that target the same pathway. The report cites three studies of improved outcomes for patients with breast cancer when combining two HER2 agents and an aromatase inhibitor with an mTOR inhibitor. Additionally, the report cites early trial results showing that combining drugs that target mTOR and insulin-like growth factor receptor (IGF-R) delays the progression of metastatic sarcoma resistant to standard treatments.
This year's ASCO report has many accompanying resources, including an audio podcast on the report's highlights with Co-executive Editor Nicholas J. Vogelzang, MD, a medical oncologist at U.S. Oncology Research, Comprehensive Cancer Centers of Nevada. The report and additional resources are available at www.cancerprogress.net/cca.
New Anti-Cancer Therapies Cited by ASCO
The report highlights the following seven newly approved cancer drugs:
- Axitinib, for patients with advanced renal cell carcinoma who have not responded to other treatments specific to this cancer.
- Vismodegib, for patients with locally advanced basal cell cancer who are not candidates for surgery or radiation and for patients whose cancer has metastasized.
- Pertuzumab, for use in combination with trastuzumab and docetaxel as a first-line treatment for patients with HER2-positive metastatic breast cancer.
- Carfilzomib, for patients with multiple myeloma whose disease progressed despite at least two prior therapies, including bortezomib and an immunomodulatory agent.
- Ziv-aflibercept, for use with FOLFIRI chemotherapy (fluorouracil, leucovorin, irinotecan) in patients with metastatic colorectal cancer that is resistant to or has progressed following an oxaliplatin-containing regimen.
- Enzalutamide, for patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.
- Regorafenib, for patients with metastatic colorectal cancer that has progressed despite standard treatments.