2012 is a fruitful year for the international cancer research community. Although cancer is still a leading cause of death in many countries and regions, countless significant, practice-changing cancer research advances have been accomplished and officially issued by the mainstream medical media around the world.
A list of 17 major advances in clinical cancer research, considered to be practice-changing, has been issued by the American Society of Clinical Oncology (ASCO) in its annual report, entitled Clinical Cancer Advances 2012:
• Everolimus (Afinitor) in hormone-receptor positive breast cancer. Everolimus, an mTOR inhibitor used in the treatment of renal cell cancer, was approved for use in combination with exemestane (Aromasin) for women with hormone-positive breast cancer that has spread despite initial treatment with an aromatase inhibitor. This indication was based on results from the 724-patient BOLERO-2 trial, which was halted early because of the benefit observed. The combination of everolimus plus exemestane increased the median time to disease progression to 10.6 months, compared with 4.1 months with exemestane alone (N Engl J Med. 2012;366:520-529).
• T-DM1 in HER2-positive metastatic breast cancer. T-DM1, which is currently awaiting approval by the US Food and Drug Administration (FDA), consists of the anti-HER2 antibody trastuzumab (Herceptin) linked to the cytotoxic emansine. "We've taught an old friend a new trick - we're using [trastuzumab] as a delivery vehicle," said one expert. In the pivotal EMILIA trial of 991 women with HER2-positive metastatic breast cancer who had stopped responding to trastuzumab, T-DM1 improved survival, compared with the current standard treatment of capecitabine (Xeloda) and lapatinib (Tykerb) (N Engl J Med. 2012;367:1783-1791). After 2 years, the median survival rates were 65.4% with T-DM1 and 47.5% with the standard combination.
• Preoperative chemo and radiation for esophageal cancers. A phase 3 trial of 366 patients with cancer of the esophagus or gastroesophageal junction showed that preoperative treatment with chemotherapy (carboplatin and paclitaxel) plus radiation, followed by surgery, yielded substantial benefits, compared with surgery alone (N Engl J Med. 2012;366:2074-2084). Patients who had preoperative treatment survived for twice as long (median overall survival, 49 vs 24 months), and 29% had a complete remission.
• Screening with flexible sigmoidoscopy reduces colorectal cancer deaths. A large American study, involving 154,000 patients with a median follow-up of 11.9 years, showed a significant decrease in the incidence of colorectal cancer (reduced by 21%) and death (26%) (N Engl J Med. 2012;366;2345-2357). This study, hailed as a landmark trial, confirmed benefits seen in previous British and Italian studies, and has prompted much discussion about how flexible sigmoidoscopy compares with colonoscopy, the preferred screening method in the United States.
• Enzalutamide (Xtandi) for late-stage prostate cancer. Enzalutamide was approved by the FDA in August for use in men with metastatic castration-resistant prostate cancer previously treated with docetaxel after the ARRIRM trial of 1199 men was stopped early because it showed a survival benefit. Median overall survival was 18.4 months with enzalutamide and 13.6 months with placebo (N Engl J Med. 2012:367:1187-1197). It is predicted that this first-in-its-class drug will be a "game-changer" in prostate cancer.
• Lenalidomide (Revlimid ) maintenance in multiple myeloma. The finding that lenalidomide delays relapse after stem cell transplantation comes from 2 placebo-controlled phase 3 trials. In the first study (N Engl J Med. 2012;366:1782-1791), conducted in 615 patients younger than 65 years, the disease returned after 41 months with lenalidomide and after 23 months with placebo; after 4 years of follow-up, more than 70% of patients were alive in both groups. In the second study (N Engl J Med. 2012;366:1759-1769), conducted in 460 patients younger than 71 years, median time to progression was 46 months with lenalidomide and 27 months with placebo. Lenalidomide also increased overall survival (35 deaths in the lenalidomide group and 53 in the placebo group). However, lenalidomide was associated with more adverse events and a higher incidence of second cancers than placebo (7%-8% vs 3%-4%), the report notes.
• Pertuzumab (Perjeta) in HER2-positive metastatic breast cancer. Pertuzumab is an anti-HER2 antibody that was approved in June in the United States and just cleared for approval in Europe. The CLEOPATRA trialshowed that adding pertuzumab to the combination of trastuzumab plus docetaxel in the initial treatment of HER2-postive breast cancer can overcome or delay the resistance that develops to trastuzumab when it is used alone. In the 808 women, the median time to progression was 18.5 months when pertuzumab was added to the initial treatment,and 12.4 months when it was not (N Engl J Med. 2012;366:109-119).
• Regorafenib (Stivarga) in metastatic colorectal cancer. This multitargeted drug was approved by the FDA in September, after the CORRECT trial showed that regorafenib extended overall survival in patients with metastatic colorectal cancer whose disease had progressed after all approved standard therapies. Median overall survival was 6.4 months with regorafenib and 5.0 months with best supportive care. These results were presented at the Gastrointestinal Cancers Symposium in January, and so far the data are available only in abstract form (J Clin Oncol. 2012;30(4 Suppl):abstract LBA385).
• Bevacizumab (Avastin) in recurrent ovarian cancer. Women with ovarian cancer who progress after platinum-based chemotherapy are then treated nonplatinum-containing chemotherapy, such as pegylated liposomal doxorubicin, topotecan, and weekly paclitaxel. The AURELIA trial of 361 women who had received up to 2 previous treatment regimens showed that median time to disease progression was better with bevacizumab plus this chemotherapy than with chemotherapy alone (6.7 vs 3.4 months). These results were presented at the 2012 ASCO annual meeting, and so far are available only in abstract form (J Clin Oncol. 2012:30:30(15 Suppl):abstract LBA5002).
• Cabozantinib (Cometriq) in medullary thyroid cancer. This drug was approved by the FDA in November on the basis of the pivotal EXAM trial of 330 patients with progressive, inoperable, metastatic, or locally advanced disease, and tumors that were actively growing. The results showed that cabozantinib improved time to disease progression over placebo (11.2 vs 4.0 months). In addition, tumor shrinkage was seen in 26% of patients in the cabozantinib group, compared with 0% in the placebo group, and these responses lasted a median of 14.6 months. These results have been presented at meetings and are available only in abstract form (J Clin Oncol2012:30:(15 Suppl):abstract 5508). Cabozantinib is also being studied in other cancer types, and "unprecedented" results were recently reported in advanced prostate cancer.
• Carboplatin and pemetrexed combination in nonsmall-cell lung cancer (NSCLC). Patients with NSCLC who have a performance score of 2 (capable of caring for themselves, but not carrying out work activities) are currently treated with a single chemotherapy, but a new study suggests they might live longer if they are treated with a 2-drug combination. This represents a "paradigm shift in the standard care for advanced NSCLC," and underscores the importance of not undertreating this patient population, according to the ASCO report. The 205-patient study showed that the combination of carboplatin plus pemetrexed increased median overall survival to 9.1 months, compared with 5.6 months for pemetrexed alone. In addition, tumor shrinkage was seen in 24% of patients in the combination group and in 10% of the monotherapy group (J Clin Oncol2012;30(15 Suppl):abstract 7506).
• Vismodegib (Erivedge) for basal cell carcinoma. Basal cell carcinoma is the most common form of skin cancer, and vismodegib is the first drug approved by the FDA for the treatment of advanced disease that has metastasized or relapsed after treatment with surgery, or for patients who are not candidates for surgery or radiation. Two studies showing efficacy (N Engl J Med. 2012;366: 2171-2179, 2180-2188) were accompanied by an editorial (N Engl J Med. 2012;366:2225-2226) declaring that vismodegib is "the greatest advance in therapy yet." One of the studies (N Engl J Med. 2012;366:2180-2188) involved 41 patients with basal cell nevus syndrome, which can lead to hundreds or thousands of lesions. During treatment with vismodegib, no tumors progressed and in some patients, all tumors regressed. However, more than half of the patients receiving vismodegib had to stop treatment because of adverse events (including loss of taste, muscle crams, weight loss, and hair loss), according to the ASCO report. It highlights the fact that vismodegib has a novel mechanism of action - blocking the Hedgehog signaling pathway - and that the drug is being investigated in other cancer types, including colorectal, stomach, and pancreatic cancers.
• Pazopanib (Votrient) for soft tissue sarcoma. Pazopanib is already marketed for the treatment of renal cell carcinoma, but this year it was approved in the United States and in Europe for use in the treatment of patients with advanced soft tissue sarcomas (excluding adipocytic sarcomas and gastrointestinal stromal tumors) who have received previous chemotherapy. The PALETTE trial of 369 such patients showed an increase in the median time to disease progression with pazopanib, compared with placebo (4.6 vs 1.6 months), although median overall survival times were similar (12.5 vs 10.7 months) (Lancet. 2012;379:1879-1886). Although this led to questions about benefit, experts treating sarcoma feel it offers an important new option for their patients. This is the first positive trial and the first new drug in sarcoma for decades, according to the ASCO report.
• Olanzapine (Zyprexa) for chemo-induced nausea and vomiting. Olanzapine, marketed as an antipsychotic drug, was shown to be an effective rescue medication for patients who were suffering from breakthrough chemotherapy-induced nausea and vomiting (CINV), despite having received standard prophylactic treatment. In 80 of 205 patients who developed breakthrough CINV, olanzapine significantly outperformed the conventional antinausea drug metoclopramide. More patients in the olanzapine group than in the metoclopramide group reported no vomiting (71% vs 32%) and no nausea (67% vs 24%). The study was presented at the 2012 ASCO annual meeting, and so far is available only in abstract form (J Clin Oncol. 2012;30(15 Suppl):abstract 9064).
• Duloxetine (Cymbalta) for chemo-induced peripheral neuropathy. Duloxetine is marketed as an antidepressant but is also approved for use in painful diabetic peripheral neuropathy. In a phase 3 trial, it was shown to be useful in alleviating pain from chemotherapy-induced peripheral neuropathy (CIPN). The trial involved 231 cancer patients who had been treated with oxaliplatin or paclitaxel and had developed CIPN, and duloxetine was associated with a greater average decrease in the pain score than placebo. These results are also available only in abstract form (J Clin Oncol 2012;30(15 Suppl):abstract CRA9013).
• Factors in elderly patients that increase chemotherapy risks. Few clinical trials are conducted specifically in the elderly, so deciding on cancer treatment in an elderly patient is difficult, the ASCO report notes. A trial published this year identified factors that are important to consider when deciding whether an elderly patient should undergo chemotherapy, and explained how they affect the risk for fatality after initiating chemotherapy (J Clin Oncol. 2012;30:1829-1834). A baseline abbreviated comprehensive geriatric assessment was carried out on 348 patients older than 70 years who were scheduled for initial chemotherapy for various cancers; advanced disease, low nutritional assessment score, and poor mobility predicted early death (in less than 6 months) after beginning chemotherapy.
• Predicting risk for chemo adverse effects in elderly patients. Another trial in elderly patients proposed a predictive model to identify those at elevated risk for adverse effects from chemotherapy (J Clin Oncol.2011;29:3457-3465). The trial involved 500 patients 59 to 91 years of age with a variety of cancers who underwent detailed assessment of tumor characteristics, laboratory tests, and geriatric status (including function, comorbidity, cognition, physiological state, social activity/support, and nutrition), and were then observed going through 1 round of chemotherapy. On the basis of responses, the researchers developed a scoring system and risk-stratification model that identify older adults at low, intermediate, and high risk for adverse events from chemotherapy.
China Medical Tribune (CMT), the main medical media in China, has just released its first annual selection of the top cancer advances of the year 2012 in China. CMT and Chinese Society of Clinical Oncology (CSCO) jointly conducted the selection, following a thorough review of recommendations from clinical oncology experts and media reports, as well as voting from experts (70%) and readers (30%). These major advances are considered to be practice-changing in clinical cancer research and patient care in China.
• Cancer diagnosis and treatment guidelines were promoted by the Ministry of Health of China
The Ministry of Health has organized experts to write cancer diagnosis and treatment guidelines since 2011 and has encouraged clinicians to learn and practice the guidelines beginning 2012. This initiative holds promise to further standardize the treatment practice of cancer in China, improve the diagnosis and treatment efficiency of common cancers in China's health care institutes, guarantee the health care quality and safety, and to increase the survival rate of cancer patients and reduce mortality.
• Establishment of "Good Pain Management Ward (GPM Ward)" and Authorization for the first group of 67 "Demonstration Wards"
The establishment of the wards has played an active role in improving health care providers' ability to diagnose and treat cancer pain, enhancing the level of awareness of cancer pain treatment for the patients and the public, regulating the usage of anesthetic analgesic drugs, as well as promoting the development of the clinical practice of standard treatment for cancer pain.
• Self-HPV detection may serve as a primary screening method for cervical cancer
A study led by Dr. Youlin Qiao from the Cancer Institute and Hospital, Chinese Academy of Medical Sciences suggested that self-HPV detection can be a practical option for women in their cervical cancer screening, although further research is still needed. Self-HPV detection can also serve as a supplemental screening method when the current cytology method fails to provide accurate screening. This study may prove to be more significant in areas that are lack of economic development and cytopathologists.
• Radiotherapy for early stage nasal lymphoma
Nasal NK/T cell lymphoma (N-NK/T-L) is a rare but highly aggressive subtype of lymphoma. In 2012, a research team led by Dr. Yexiong Li from the Cancer Institute and Hospital, Chinese Academy of Medical Sciences brought important insights into the treatment of this lethal cancer that is under-investigated due to its rarity. Dr. Li conducted the first study in the field reporting the treatment effect of Intensity Modulated Radiation Therapy (IMRT) for early stage N-NK/T-L. His second study involved 87 patients with N-NK/T-L and the results suggested that high dose Extended-field Radiation Therapy (EFRT) alone can cure the disease when treated at stage I.
• Gefitinib as maintenance therapy for non-small cell lung cancer
Led by Dr. Li Zhang's research group at Sun Yat-sen University Cancer Center, a clinical study, known as "INFORM," has demonstrated that targeted cancer drug gefitinib (trade name IRESSA®) is an effective maintenance therapy that can prolong progression-free survival time for certain patients with late stage non-small cell lung cancer (NSCLC). The drug is especially effective for those with activating mutations in the genes encoding epidermal growth factor receptor (EGFR). This finding has great guiding significance for oncologists to make clinical treatment decisions.
• Drug usage guidelines for preventing life-threatening complications in cancer patients
Cancer patients are at high risk of developing deep vein thrombosis which is a very serious condition that can cause permanent damage to the leg, and may further lead to a life-threatening embolism in the lungs. The Guidelines for using low molecular weight heparin (LMWH) to prevent these complications not only can improve patients' prognosis and reduce total medical cost, but also can improve patients' life quality and survival time without increasing the risk of bleeding and other complications.
• Chemotherapy reduces EGFR mutation frequency in patients with non-small cell lung cancer (NSCLC)
Many patients with non-small cell lung cancer carry mutations in the genes coding for epidermal growth factor receptor (EGFR). Individuals who have mutations in the EGFR gene have better responses when treated with certain personalized and targeted therapies. Recently Dr. Jie Wang from Peking University Cancer Hospital discovered that chemotherapy can actually reduce EGFR mutation frequency in NSCLC patients. This study revealed the influence of chemotherapy on EGFR mutations and helps to guide personalized treatment for lung cancer patients.
• The CellSearch used for prognostic analysis of breast cance
Dr. Zefei Jiang from Cancer Center Academy Military Medical Sciences (AMMS) in Beijing recently developed CellSearch, a new technique that can precisely detect the metastatic cancer cells in the blood circulation of patients with advanced breast cancer. This novel tool has great clinical value for analyzing patients' prognosis, monitoring post-operational recurrence and metastases, evaluating treatment outcomes, and choosing personalized treatment strategies.
• A multi-center clinical trial: using sunitinib as first line treatment for advanced renal cell carcinoma
Last year, Dr. Shukui Qin from the Oncology Center of Chinese People's Liberation Army (PLA) 81st Hospital successfully led the largest multi-center clinical trial studying the effect of sunitinib (trade name SUTENT®) as first line treatment for metastatic renal cell carcinoma (mRCC) in China. Results suggested that sunitinib could be an effective therapeutic drug for Chinese patients with mRCC. This study also plays a guiding role for future clinical and research works on sunitinib and mRCC in China.
• The establishment of clinical models for targeted therapy EGFR-TKI
EGFR-TKI is a group of drugs that specifically inhibit epidermal growth factor receptor in tumors. Dr. Yilong Wu from Guangdong Lung Cancer Institute, Guangdong General Hospital found that lung cancer patients with brain metastases may benefit from EGFR-TKI treatment. Brain metastases are common in patients with non-small cell lung cancer (NSCLC) and are difficult to treat. This study has brought a clear treatment solution to lung cancer patients with asymptomatic brain metastases, which is of great social value. In his second study, Dr. Wu focused on the drug resistance issue of TKI drugs, a problem faced by clinicians every day. Dr. Wu proposed personalized treatment plans for different patients, allowing each of them to benefit the most from their treatment. This study has brought a new concept of treatment to the field.
While cancer remains the leading cause of death in Canada - a recent report by the Canadian Cancer Society estimated that in 2012, 200 Canadians died of cancer every day - the past 30 years have seen major developments in understanding the genetics, biology and treatment of the disease.
According to the Canadian Cancer Society, the cancer death rate dropped 21 per cent in men and nine per cent in women between 1988 and 2007. Investigations leading to new explanations and solutions to cancer are in full force in the quest to reduce mortality rates and enhance the quality of life for Canadians living with and beyond cancer. Also on its report, Canadian Cancer Society compiles the top 10 cancer research stories of 2012:
•Deadly Form Of Breast Cancer Decoded
Triple negative breast cancer is a difficult form of cancer to treat, but for the first time ever, an international team of scientists have decoded its genetic makeup. Knowing more about these genes could change the way the disease is diagnosed and change treatments for the next generation, creating more personalized care.
•New Ways To Treat Malignant Childhood Brain Cancer
Dr. Michael Taylor, based in Toronto, was part of the international MAGIC (Medulloblastoma Advanced Genomics International Consortium) team of experts that identified abnormalities that lead to the development of the malignant brain tumour medulloblastama. This discovery has identified more effective treatments and may spare children the side effects of unnecessary radiation.
•Improving Survival For Patients With Rare Form Of Pancreatic Cancer
Though there are typically poor survival rates for those living with pancreatic cancer, new findings may improve these rates of survival. An NCIC Clinical Trials Group study found that patients with a rare form of pancreatic cancer - periampullary adenocarcinoma - live longer if they are treated with surgery as well as chemotherapy.
•Hodgkin Lymphoma Patients Live Longer With Chemotherapy Alone
A trial led by the NCIC Clinical Trials Group found that patients with limited-stage Hodgkin lymphoma live longer when treated with standard chemotherapy compared with those who are also receiving radiation. This will allow patients to avoid long-term side effects of radiation.
•Key Barriers To Palliative Care Identified
A study led by Dr. Camilla Zimmermann in Toronto found that Canadian oncologists refer terminally ill cancer patients to palliative care too late - sometimes not until the final few days. The availability and comprehensiveness of palliative care services were identified as key barriers. It was found that referring patients earlier allows care teams to relieve symptoms and distress, provide appropriate social services, and give advanced care advice to improve the quality of life for cancer patients.
•Natural Sea Sponge Can Prevent Muscle Wasting
Muscle wasting, also referred to as Cachexia, is the loss of weight or muscle often induced by cancer. Approximately 30 per cent of people with cancer die due to muscle wasting. Dr. Imed Gallouzi and his research team in Montreal found that a natural product from sea sponges prevents muscle wasting in mice. This study is the first to show a potential treatment option for those affected by muscle wasting.
•Drug Destroys Human Cancer Stem Cells But Spares Healthy Ones
Dr. Mick Bhatia, an international leader in cancer stem cell research, discovered that the drug thioridazine can successfully kill cancer stem cells responsible for initiating leukemias without causing any harm to normal stem cells. This is an important discovery, as cancer stem cells can sustain the growth of cancer and are also a common factor in cancer recurrence.
•Smarter Treatments Developed For Rare Young Adult Cancer
Dr.Torsten Nielsen and his Vancouver-based research team have unravelled how the genetic mutation which leads to the growth of a rare and often fatal form of cancer (synovial sarcoma) interacts with proteins to cause cancer. The researchers found that there are certain drugs used to suppress these proteins that can kill tumour cells.
•Vitamin D Controls Proteins To Stop The Growth Of Cancer
Dr. John White and his research group in Montreal studied a protein called the cMYC protein, which is elevated in at least 50 per cent of cancers. Researchers found that vitamin D can block cMYC. This evidence will spark future studies to understand the role Vitamin D plays in stopping cancer development and growth.
•Mefloquine Drug Shows Promise In Fighting Cancer
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow that can become severe if not treated quickly. Dr. Aaron Schimmer and colleagues in Toronto tested several drugs to determine whether any of them could target AML cells. The researchers found that mefloquine, a medication generally used to treat malaria, specifically causes AML cancer cells to burst.