MAJOR CANCER ADVANCES IN 2010

November 24, 2010 — Major and notable advances in clinical cancer research made during the past year are highlighted in the annual report from the American Society of Clinical Oncology (ASCO), which was published online November 15 in the Journal of Clinical Oncology.

Significant progress is being made on the front lines of clinical cancer research, ASCO president George Sledge, MD, writes in the introduction to the report.

The 12 studies described as "major advances" are detailed below. Many of these were presented at the ASCO annual meeting and were reported by Medscape Medical News at the time.

Doublet chemotherapy improved survival in elderly patients with lung cancer, compared with single-agent chemotherapy; the combination of carboplatin and paclitaxel proved better than single-agent gemcitabine or vinorelbine.

Best-ever survival rates in metastatic pancreatic cancer were reported with chemotherapy combination. In this phase 3 trial, the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) bested the standard single-agent therapy, gemcitabine (Gemzar).

Bevacizumab (Avastin) extended progression-free survival in advanced ovarian cancer; the biologic was added to standard chemotherapy with carboplatin and paclitaxel.

Ipilimumab improved survival in advanced melanoma, the first time that a survival benefit has been shown in a phase 3 trial in advanced melanoma. The drug is a monoclonal antibody that keeps T cells activated, and is currently awaiting approval.

Hypofractionated radiotherapy for early-stage breast cancer, comprising a shorter 3-week course of a higher dose of radiation, was just as effective as the standard 5-week course (N Engl J Med. 2010;362:513-520).

Crizotinib, a specific ALK inhibitor, produced dramatic response rates in a phase 1 trial in patients with lung cancer and the ALK mutation (found in about 20% of patients); more than two thirds of patients showed tumor shrinkage.

PLX4032, which targets BRAF, showed very high response rates in patients with advanced melanoma and the BRAF mutation (found in about 50% of patients).

Palliative care added to chemotherapy in lung cancer patients significantly improved survival (N Engl J Med. 2010;363:733-742). This study was described as "paradigm shifting" in an editorial that accompanied the study (N Engl J Med. 2010;363:781-782).

In the first large study to evaluate insomnia in patients undergoing chemotherapy, sleep problems were found to affect more than three quarters of these patients, which is nearly 3 times the rate found in the general population (J Clin Oncol. 2009;28:292-298).

The cancer vaccine sipuleucel-T (Provenge) was approved for metastatic hormone-refractory prostate cancer; it is the first immunotherapeutic for this disease.

New chemotherapy for prostate cancer — cabazitaxel (Jevtana) — was approved for use in advanced hormone-refractory prostate cancer in patients who had failed on docetaxel.

Long-term risks for cardiac problems were found among children and adolescent cancer survivors who were treated with anthracyclines and/or chest radiation (BMJ. 2009;339:b4606); they were 6 times more likely to develop congestive heart failure than their cancer-free siblings.

Other Notable Advances

The report describes another 53 studies as "notable advances." Among them, according to therapeutic category, are the following.

Hematological Malignancies

Dasatinib (Sprycel) and nilotinib (Tasigna) might provide even more effective options against chronic myeloid leukemia than the original tyrosine kinase inhibitor imatinib (Gleevec).

Lenalidomide maintenance therapy slows myeloma progression.

Better treatment of follicular lymphoma was suggested in 2 phase 3 studies: when bendamustine (Treanda) was added to rituximab (Rituxan) and when rituximab was used for 2 years of maintenance therapy (PRIMA trial).

Pralatrexate (Folotyn) was approved as single-agent therapy for relapsed or refractory peripheral T cell lymphoma, based on the phase 2 PROPEL trial. The drug works by inhibiting RFC-1, a protein overexpressed in T cell lymphoma.

Ofatumumab (Arzerra) was approved for relapsed or resistant chronic lymphocytic leukemia on the basis of a single-group trial of patients who had already failed treatment with fludarabine and alemtuzumab. The drug is a monoclonal antibody that targets the CD20 protein on B cells.

Breast Cancer

Eribulin (Halaven) improved overall survival in metastatic breast cancer in the phase 3 EMBRACE study, which led to approval of the drug for late-stage breast cancer in patients who have received at least 2 previous chemotherapy regimens.

Immunohistochemistry to find micrometastases in bone marrow and sentinel lymph nodes is unnecessary in early breast cancer.

Removing fewer lymph nodes in sentinel node-positive breast cancer does not impair survival, according to data from the ASCOSOG Z0010 trial.

Data from the National Surgical Adjuvant Breast and Bowel Project involving 5611 women have shown that a negative sentinel node is adequate to confirm lack of cancer spread (2010 ASCO annual meeting: Abstract LBA505)

Gastrointestinal Cancers

Sunitinib (Sutent) delays cancer spread for patients with pancreatic neuroendocrine tumors.

Gastrointestinal stromal tumor mutations predict recurrence rates and might guide treatment choice (2010 ASCO annual meeting: Abstract 10006).

KRAS mutation status has been used to decide whether to add cetuximab (Erbitux) to chemotherapy for the treatment of metastatic colon cancer, but new data suggest that BRAF status is also important; patients with normal forms of KRAS and BRAF benefited most (2010 ASCO annual meeting: Abstract 3506). Another study suggests that BRAF status is useful for predicting outcomes (2010 ASCO annual meeting: Abstract 3504).

Genitourinary and Gynecological Cancers

Watchful waiting is an option for patients with low-risk prostate cancer (J Clin Oncol. 2010;28:126-131).

Pazopanib (Votrient) was approved for kidney cancer on the basis of results from a phase 3 study showing improved survival (J Clin Oncol. 2010;28:1061-1068).

A new screening approach for ovarian cancer shows promise for postmenopausal women at average risk. The approach is based on a combination of trends in CA-125 blood test results and a patient's age, followed by transvaginal sonogram. Another large study of this approach is ongoing in the United Kingdom; results are expected in 2015.

Head and Neck Cancers

Survival is better in oropharyngeal tumors that are positive for human papillomavirus.

An accelerated radiotherapy schedule is more effective in head and neck cancer in resource-poor countries (Lancet Oncol. 2010;11:553-560).

Sentinel node biopsy shows potential for early-stage oral cancer (J Clin Oncol. 2010;28:1395-1400).

Radiotherapy quality and protocol compliance are keys to head and neck survival (J Clin Oncol. 2010;28:2996-3001).

Lung Cancer

Stereotactic radiation is a potential alternative for patients with inoperable early-stage lung cancer (JAMA. 2010;303:1070-1076).

Melanoma

Indoor tanning raises the risk for melanoma, according to a case–controlled study (Cancer Epidemiol Biomarkers Prev. 2010;19:1557-1568).

Alpha interferon after surgery improves overall survival in patients with melanoma, according to a meta-analysis of 14 trials with a total of 8122 high-risk melanoma patients (J Natl Cancer Inst. 2010;102:493-501).

Pediatric Cancers

Genetic variants are linked to hearing loss in children who received cisplatin (Nat Genet. 2009;41:1345-1349).

Childhood glioma does not respond to combination bevacizumab plus irinotecan, even though adult glioma does (J Clin Oncol. 2010;28:3069-3075).

The late effects of childhood cancer substantially reduce life expectancy (Ann Intern Med. 2010;152:409-417).

Imatinib added to chemotherapy improves event-free survival in children with high-risk acute lymphoblastic leukemia (J Clin Oncol. 2009;27:5175-5181).

Prevention and Screening

Cancer incidence and cancer death rates have declined in the United States (Cancer. 2010;116:544-573).

One-time sigmoidoscopy screening reduces colon cancer incidence and death (Lancet. 2010;375:1624-1633).

The mammography recommendation has been changed for women 40 to 49 years of age by the US Preventive Services Task Force; it no longer recommends routine mammography, but instead recommends that patients discuss the issue with their doctor because the risks outweigh potential benefits in this age group (Ann Intern Med. 2009;151:716-726). Screening advocates were outraged, and said it would result in deaths from breast cancer.

Quality of Care and Quality of Life

Yoga improves sleep and quality of life, and reduces fatigue in cancer survivors.

Telephone-based patient management improves depression and pain in cancer patients (JAMA. 2010;304:163-171).

Poor communication and other medical conditions affect decision-making about surgery for early-stage lung cancer (JAMA. 2010;303: 2368-2376).

Cancer Disparities

Disparities in cancer survival are most notable in hormonally driven cancers, such as breast, prostate, and ovarian cancer (J Natl Cancer Inst. 2009:101;984-992).

An association has been found between African ancestry and triple-negative breast cancer (J Clin Oncol. 2009:27:4515-4521 and Cancer. 2010;116:4926-4932).

Socioeconomic status has been shown to play a major role in racial disparities in colon cancer outcomes (Cancer. 2010;116:713-722).

Race is associated with response to chemotherapy in advanced colorectal cancer (J Clin Oncol. 2009;27:4109-4115).

J Clin Oncol. Published online November 15, 2010. Abstract