Colorectal cancer<unk>  was approved in the United States in February 2004, for use in metastatic colorectal cancer when used with standard chemotherapy treatment (as first-line treatment). In June 2006, it was approved with 5-fluorouracil-based therapy for second-line metastatic colorectal cancer. It was approved by the European Medicines Agency (EMA) in January 2005, for use in colorectal cancer.<unk>  has also been examined as an add on to other chemotherapy drugs in people with non-metastatic colon cancer. The data from two large randomized studies showed no benefit in preventing the cancer from returning and a potential to cause harm in this setting. In the EU,<unk>  in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of adults with metastatic carcinoma of the colon or rectum. Lung cancer In 2006, the U.S. Food and Drug Administration (FDA) approved<unk>  for use in first-line advanced nonsquamous non-small cell lung cancer in combination with carboplatin/paclitaxel chemotherapy. The approval was based on the pivotal study E4599 (conducted by the Eastern Cooperative Oncology Group), which demonstrated a two-month improvement in overall survival in patients treated with<unk>  (Sandler, et al. NEJM 2004). A preplanned analysis of histology in E4599 demonstrated a four-month median survival benefit with<unk>  for people with adenocarcinoma (Sandler, et al. JTO 2010); adenocarcinoma represents approximately 85% of all non-squamous cell carcinomas of the lung. A subsequent European clinical trial, AVAiL, was first reported in 2009 and confirmed the significant improvement in progression-free survival shown in E4599 (Reck, et al. Ann. Oncol. 2010). An overall survival benefit was not demonstrated in patients treated with<unk> ; however, this may be due to the more limited use of<unk>  as maintenance treatment in AVAiL versus E4599 (this differential effect is also apparent in the European vs US trials of<unk>  in colorectal cancer: Tyagi and Grothey, Clin Colorectal Cancer, 2006). As an anti-angiogenic agent, there is no mechanistic rationale for stopping<unk>  before disease progression. Stated another way, the survival benefits achieved with<unk>  can only be expected when used in accordance with the clinical evidence: continued until disease progression or treatment-limiting side effects. Another large European-based clinical trial with<unk>  in lung cancer, AVAPERL, was reported in October 2011 (Barlesi, et al. ECCM 2011). First-line patients were treated with<unk>  plus cisplatin/pemetrexed for four cycles, and then randomized to receive maintenance treatment with either<unk> /pemetrexed or<unk>  alone until disease progression. Maintenance treatment with<unk> /pemetrexed demonstrated a 50% reduction in risk of progression vs<unk>  alone (median PFS: 10.2 vs 6.6 months). Maintenance treatment with<unk> /pemetrexed did not confer a significant increase in overall survival vs<unk>  alone on follow up analysis. The National Comprehensive Cancer Network recommends<unk>  as standard first-line treatment in combination with any platinum-based chemotherapy, followed by maintenance<unk>  until disease progression. Higher doses are usually given with carboplatin-based chemotherapy, whereas the lower dose is usually given with cisplatin-based chemotherapy. In the EU,<unk> , in addition to platinum-based chemotherapy, is indicated for first-line treatment of adults with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology.<unk> , in combination with erlotinib, is indicated for first-line treatment of adults with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations. Breast cancer In December 2010, the U.S. Food and Drug Administration (FDA) notified its intention to remove the breast cancer indication from<unk> , saying that it had not been shown to be safe and effective in breast cancer patients. The combined data from four different clinical trials showed that<unk>  neither prolonged overall survival nor slowed disease progression sufficiently to outweigh the risk it presents to patients. This only prevented Genentech from marketing<unk>  for breast cancer. Doctors are free to prescribe<unk>  off label, although insurance companies are less likely to approve off-label treatments. In June 2011, an FDA panel unanimously rejected an appeal by Roche. A panel of cancer experts ruled for a second time that Avastin should no longer be used in breast cancer patients, clearing the way for the U.S. government to remove its endorsement from the drug. The June 2011 meeting of the FDA's oncologic drug advisory committee was the last step in an appeal by the drug's maker. The committee concluded that breast cancer clinical studies of patients taking Avastin have shown no advantage in survival rates, no improvement in quality of life, and significant side effects. On 11 October 2011, the U.S. Food and Drug Administration (FDA) announced that the agency was revoking the agency's approval of the breast cancer indication for<unk>  after concluding that the drug had not been shown to be safe and effective for that use. In the EU,<unk>  in combination with paclitaxel is indicated for first-line treatment of adults with metastatic breast cancer.<unk>  in combination with capecitabine is indicated for first-line treatment of adults with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate. Renal cancers In certain renal (kidney) cancers,<unk>  improves the progression free survival time but not survival time. In 2009, the FDA approved<unk>  for use in metastatic renal cell cancer (a form of kidney cancer). following earlier reports of activity EU approval was granted in 2007. In the EU,<unk>  in combination with interferon alfa-2a is indicated for first-line treatment of adults with advanced and/or metastatic renal cell cancer. Brain cancers<unk>  slows tumor growth but does not affect overall survival in people with glioblastoma multiforme. The FDA granted accelerated approval for the treatment of recurrent glioblastoma multiforme in May 2009. A 2018 Cochrane review deemed there to not be good evidence for its use in recurrences either. Eye disease Many diseases of the eye, such as age-related macular degeneration (AMD) and diabetic retinopathy, damage the retina and cause blindness when blood vessels around the retina grow abnormally and leak fluid, causing the layers of the retina to separate. This abnormal growth is caused by VEGF, so<unk>  has been successfully used to inhibit VEGF and slow this growth.<unk>  has been used by ophthalmologists in an off-label use as an intravitreal agent in the treatment of proliferative (neovascular) eye diseases, particularly for choroidal neovascular membrane (CNV) in AMD. The injection of 1.25–2.5 mg of<unk>  into the vitreous cavity has been performed without significant intraocular toxicity. Many retina specialists have noted impressive results in the setting of CNV, proliferative diabetic retinopathy, neovascular glaucoma, diabetic macular edema, retinopathy of prematurity and macular edema secondary to retinal vein occlusions. Several reviews concluded that similar results concerning effects and safety were obtained using either<unk>  or ranibizumab. Ovarian cancer In 2018, the U.S. Food and Drug Administration (FDA) approved<unk>  in combination with chemotherapy for stage III or IV of ovarian cancer after initial surgical operation, followed by single-agent<unk> . The approval was based on a study of the addition of<unk>  to carboplatin and paclitaxel. Progression-free survival was increased to 18 months from 13 months. In the EU,<unk> , in combination with carboplatin and paclitaxel is indicated for the front-line treatment of adults with advanced (International Federation of Gynecology and Obstetrics (FIGO) stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.<unk> , in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel, is indicated for treatment of adults with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with<unk>  or other VEGF inhibitors or VEGF receptor-targeted agents. In May 2020, the Food and Drug Administration expanded the indication of olaparib to include its combination with<unk>  for first-line maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability. Cervical cancer In the EU,<unk> , in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in people who cannot receive platinum therapy, is indicated for the treatment of adults with persistent, recurrent, or metastatic carcinoma of the cervix. Administration<unk>  is usually given intravenously every 14 days. In colon cancer, it is given in combination with the chemotherapy drug 5-FU (5-fluorouracil), leucovorin, and oxaliplatin or irinotecan. For treatment of eye diseases it is injected intravitreously. Off-label use for age-related macular degeneration (AMD) Dr Philip Rosenfeld developed off-label use of<unk>  for age-related macular degeneration.
Bevacizumab
Necitumumab
Bortezomib
Panitumumab
Sunitinib
Ranibizumab
Ruxolitinib
Ceritinib