The past year in oncology was highlighted by the continuation of breakthroughs in targeted therapies—with new treatments receiving US Food and Drug Administration (FDA) approval for non–small-cell lung cancer (NSCLC), lymphoma, and melanoma. The year was also marked by a controversial recommendation on prostate-specific antigen (PSA) screening, revocation of the FDA's approval of bevacizumab (Avastin) for breast cancer, and a practice-changing study comparing sentinel lymph node dissection to axillary lymph node dissection in patients with breast cancer. Below are some of 2011's top stories.
FDA Drug Approvals of Note
Abiraterone acetate (Zytiga) in conjunction with prednisone was approved for treatment of patients with metastatic castration-resistant prostate cancer who have received prior docetaxel. The phase III trial that led to the approval observed that patients who received abiraterone acetate had a survival benefit of 3.9 months compared with those who received placebo (14.8 months vs 10.9 months).
Brentuximab vedotin (Adcetris), a CD30-directed antibody-drug conjugate, was approved for the treatment of refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma (ALCL). It marks the first new FDA-approved treatment for Hodgkin lymphoma in over 30 years, and the first treatment specifically indicated for ALCL.
Two trials studying brentuximab found positive results. The first trial, involving 102 patients with Hodgkin lymphoma, found an objective response rate of 75% and complete remissions in 34% of patients. The average duration of response was 6.7 months. A second trial, which included 58 patients with ALCL, found an objective response rate of 86% and complete remissions in 53% of patients. The median response duration was 12.6 months.
Crizotinib (Xalkori) was approved for the treatment of locally advanced or metastatic NSCLC in patients who express an abnormal anaplastic lymphoma kinase (ALK) gene. In a study presented at the American Society of Clinical Oncology (ASCO) annual meeting, 82 ALK-positive patients treated with crizotinib had an overall survival of 77% after 1 year and 64% after 2 years. By comparison, ALK-positive patients who were not treated with crizotinib had an overall survival of 73% after 1 year and 33% after 2 years.
Ipilimumab (Yervoy), which works by blocking cytotoxic T-lymphocyte–associated antigen 4, thereby enhancing antitumor T-cell responses, was approved for patients with late-stage melanoma. In data presented at ASCO, a significant improvement in overall survival was observed in patients treated with ipilimumab plus dacarbazine vs dacarbazine alone (47.3% vs 36.3%, respectively, at 1 year, and 28.5% vs 17.9% at 2 years).
Vemurafenib (Zelboraf) was also approved for the treatment of metastatic or unresectable melanoma. Vemurafenib specifically targets patients whose tumors express the BRAF V600E gene mutation. In a phase III trial comparing vemurafenib with dacarbazine, overall survival after 6 months was 84% in the vemurafenib group and 64% in the dacarbazine group.
PSA Screening Guidelines
Based on a review of five clinical trials conducted between 2007 and 2010, the US Preventive Services Task Force (USPSTF) stated that PSA screening should no longer be routinely conducted for healthy men of all ages, saying that evidence shows that the test does not save lives and that the potential benefits of the screening do not outweigh the potential harm of complications from evaluations and treatments.
Lymph Node Dissection in Breast Cancer
Although it is currently the standard of care for patients with sentinel lymph node metastasis, axillary lymph node dissection (ALND) carries the risk of serious complications. Sentinel lymph node dissection (SLND) was developed to decrease these risks while still accurately staging lymph nodes. Results of a phase III trial published in JAMA found that the use of SLND was not statistically inferior to ALND in terms of overall survival (P = .008). The 5-year overall survival rates were 92.5% in the SLND-alone group and 91.8% in the ALND group. Disease-free survival did not vary between the groups. Morbidity, however, was much higher in the ALND group: the rates of wound infections, axillary seromas, and lymphedema were all significantly higher.
Progress in Pancreatic Cancer
Along with two new treatments receiving approval for the treatment of pancreatic neuroendocrine tumors—sunitinib malate (Sutent), and everolimus (Afinitor) for the treatment of advanced tumors—progress was also made in the treatment of metastatic pancreatic cancer. The use of the FOLFIRINOX regimen (oxaliplatin [Eloxatin], irinotecan, fluorouracil, and leucovorin) was compared with the current standard of care, gemcitabine (Gemzar). The study involved 342 patients and found that the median overall survival in the FOLFIRINOX group was 11.1 months, compared with 6.8 months in the gemcitabine group (P < .001). Due to significantly greater toxicity associated with the FOLFIRINOX regimen, one of the criteria for inclusion was an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
Bevacizumab made headlines throughout 2011, largely for the controversy over its indication for the treatment of metastatic breast cancer, but also for results presented at ASCO suggesting promise for its use in treating patients with ovarian cancer.
Breast cancer approval revoked
In November, the breast cancer approval of bevacizumab was revoked by the FDA due to the potentially life-threatening side effects associated with the treatment. It had been approved for metastatic breast cancer in February 2008 based on promising results from a study that suggested that the drug could provide a meaningful increase in progression-free survival, but data later showed that along with an increase in adverse effects, there was no increase in overall survival.
Two studies, the OCEANS and ICON 7 trials, showed positive trends in overall survival and progression-free survival. In the OCEANS trial, interim overall survival results favored the use of bevacizumab, with a median overall survival of 35.5 months for patients in the bevacizumab-plus-chemotherapy arm, compared with 29.9 months in the chemotherapy-alone arm. The results are not yet mature, however.
In the ICON 7 trial, data at 19 months showed an improvement in progression-free survival for patients receiving bevacizumab plus chemotherapy compared with chemotherapy alone (19.8 months vs 17.4 months). The overall survival interim analysis showed that at a median follow-up of 28 months, the risk of death in high-risk patients was reduced by 36% in those who received bevacizumab.