The past year has brought advances in the treatment of a broad range of cancers. From November 2015 through October 2016, the FDA approved eight new cancer treatments and 12 new uses of previously approved cancer therapies (Table 1). The new approvals include immunotherapies for bladder cancer and multiple myeloma and targeted treatments for hard-to-treat forms of lung and kidney cancers, chronic lymphocytic leukemia (CLL), and multiple myeloma. New-use approvals have broadened treatment options for patients with melanoma, sarcoma, CLL, lymphoma, neuroendocrine tumors, and breast, lung, kidney, and head and neck cancers. In addition, the FDA approved the first liquid biopsy test in 2016.
Each year, 14 million people around the world learn that they have cancer. Because cancer is mostly a disease of aging, cancer occurrences are expected to increase as human lifespans are extended. Although prevention is the ultimate goal, many factors that contribute to cancer cannot be controlled. Advances in cancer treatment will therefore remain a key part of reducing the global burden of cancer.
In addition to the growing success seen with immunotherapy, 2016 was marked by a wave of advances in precision medicine–based approaches. They include treatments directed at novel molecular targets, new types of treatment, and new ways to combine traditional cancer treatments.
After 20 years, a promising new treatment of acute myeloid leukemia.
Acute myeloid leukemia (AML) is the second most common type of leukemia diagnosed in both adults and children. In 2016, an estimated 19,950 people of all ages in the United States were diagnosed with AML. This type of cancer is difficult to treat, and only 27% of patients survive 5 years after diagnosis.46 More information on AML can be found on Cancer.Net.
There have been no effective new treatments for AML since the 1990s. In 2015, researchers reported preliminary findings, which may lead to a new standard of care for approximately one-third of patients with AML, those with mutations in a gene called FLT3 (this study was funded in part by a grant from the NCI).47 Patients with FMS-related tyrosine kinase 3 (FLT3)–positive AML have a poor prognosis and a high chance of relapse.
In a large clinical trial, previously untreated patients who received a therapy targeting FLT3 called midostaurin, combined with standard chemotherapy, lived years longer than those who received chemotherapy alone. The median survival was 75 months among patients who received midostaurin with chemotherapy and only 26 months among those who received placebo with chemotherapy. Midostaurin also more than doubled the median event-free survival (defined as death, relapse, or no complete remission within 61 days) achieved with chemotherapy alone (8 v. 3.6 months).
The overall rates of severe adverse effects and treatment-related deaths were similar between the midostaurin and placebo groups. With 717 patients, this is the largest clinical trial of patients with FLT3-positive AML to date to our knowledge.
New treatment targeting common marker improves outcomes after acute lymphoblastic leukemia relapse.
In 2016, an estimated 2,636 adults in the United States were diagnosed with acute lymphoblastic leukemia (ALL).48 Although a majority of adults with ALL achieve complete remission after initial therapy, many eventually relapse. The prognosis for such patients is poor, and more effective treatments are urgently needed.
One new treatment, inotuzumab ozogamicin, may improve outcomes for older people with recurrent ALL, according to an ongoing clinical trial.49 Inotuzumab ozogamicin belongs to a new class of cancer treatments known as antibody–drug conjugates (ADCs). These comprise an antibody chemically linked to a powerful cancer drug called calicheamicin. The antibody targets the CD22 molecule, found on tumor cells in 90% of patients with B-cell ALL, and helps deliver calicheamicin to leukemia cells.
In this late-stage trial, patients were randomly assigned to receive inotuzumab ozogamicin or standard intensive chemotherapy. The rate of complete remission was more than two-fold higher in the inotuzumab ozogamicin group compared with the standard therapy group (81% v. 29%). The median time until cancer worsened was longer in the inotuzumab ozogamicin group than in the standard therapy group (5 v. 1.8 months), and the median survival was longer as well (7.7 v. 6.7 months).
A major adverse effect of inotuzumab ozogamicin was veno-occlusive liver disease, which occurred in 11% of patients. Inotuzumab ozogamicin is likely to become a new standard of care for older adult patients with relapsed or refractory B-cell ALL.
Progress in treating advanced, ALK-positive NSCLC.
Approximately 3% to 7% of NSCLCs are anaplastic lymphoma kinase (ALK) positive, meaning that the cancers carry a genetic change known as ALK gene rearrangement. The first treatment to specifically target ALK-positive tumors, crizotinib, was approved by the FDA in 2011. Although crizotinib shrinks tumors in a large proportion of patients, most experience a relapse within the first year of treatment.
To address the challenge of crizotinib resistance, researchers have been developing more potent, next-generation ALK inhibitors. One such treatment, alectinib, has shown encouraging results in patients with crizotinib-resistant, advanced NSCLC, including those with brain metastases.50 In an early-stage clinical trial, 48% of patients responded to alectinib, with a median duration of response of 13.5 months.
Notably, in 75% of patients with NSCLC and brain metastases, brain lesions shrank with alectinib. This is a promising finding, because chemotherapy has had limited efficacy in the central nervous system (CNS), with response rates of only 45%. In late 2015, the FDA approved alectinib for people with ALK-positive NSCLC who cannot tolerate crizotinib or whose cancer worsens after crizotinib.51 Overall, alectinib was well tolerated, with the most frequently reported adverse effects being nausea and diarrhea. Severe liver enzyme abnormalities occurred in 6% of patients.
Preliminary findings from an ongoing late-stage clinical trial suggest that alectinib may also help previously untreated patients with advanced, ALK-positive NSCLC.52 In this study, tumors shrank in 92% of patients treated with alectinib compared with 79% of those treated with crizotinib. Patients who received alectinib had a 66% lower risk of disease worsening than those treated with crizotinib.
Moreover, alectinib was better tolerated than crizotinib, causing fewer adverse effects. Only one adverse effect, constipation, occurred in more than 30% of patients in the alectinib group. In contrast, several adverse effects, including nausea, diarrhea, vomiting, and visual disturbance, occurred in more than half of patients treated with crizotinib. Another worldwide phase III trial of this same treatment comparison (ClinicalTrials.gov identifier: NCT02075840) is underway.
New regimen halts multiple myeloma progression.
Multiple myeloma is a cancer of plasma cells, which are found in the bone marrow and make antibodies to fight infections. Abnormal plasma cells can crowd out or suppress the growth of other cells in the bone marrow, resulting in anemia, excessive bleeding, and decreased ability to fight infections.
In 2016, an estimated 30,300 people in the United States were diagnosed with multiple myeloma.53 Multiple myeloma often recurs despite treatment. Fewer than half of people with multiple myeloma will live 5 or more years after diagnosis.
Early findings from a late-stage trial suggest that a three-drug combination may improve outcomes for patients with recurrent or treatment-resistant multiple myeloma.54 The new regimen adds the novel therapy daratumumab to a standard combination of bortezomib and dexamethasone.
Treatment that incorporated daratumumab resulted in a 70% lower risk of cancer progression than the standard two-drug regimen. In addition, partial response rates were increased from 29% to 59% with daratumumab, and complete response rates from 9% to 19%. Treatment-related adverse effects were generally similar between the two groups. However, low platelet counts, peripheral neuropathy, diarrhea, and anemia occurred more frequently with the daratumumab regimen.
Daratumumab targets a molecule on plasma cells called CD38. It is one of the first cancer treatments with a two-pronged mode of action: it has the ability to destroy cancer cells directly and coax the immune system to attack the cancer. On the basis of results of an earlier clinical trial, the FDA granted daratumumab accelerated approval for the treatment of multiple myeloma in 2015.
Longer patient follow-up is required to determine if the addition of daratumumab helps patients live longer. Meanwhile, a clinical trial of daratumumab combined with a different standard regimen for patients with recurrent multiple myeloma is underway (ClinicalTrials.gov identifier: NCT01615029). Additional clinical trials testing various daratumumab-based regimens in patients with previously untreated multiple myeloma are also in progress (ClinicalTrials.gov identifiers: NCT02252172 and NCT02195479).
New class of targeted treatments for advanced breast cancer.
Hormone receptor–positive breast cancer is the most common type of breast cancer. Although hormone (antiestrogen) therapy is the standard of care for patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer, its clinical benefit is modest, and treatment resistance remains a significant challenge.
In 2016, researchers reported updated results from a large clinical trial of a new targeted treatment of metastatic breast cancer: palbociclib.55 Palbociclib is a pill that works by blocking two molecules involved in breast cancer resistance to hormone therapy: cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6). CDK4/6 inhibitors are a new class of targeted treatments that may have a role in many different types of cancer in the future.
The study enrolled women with hormone receptor–positive, HER2-negative metastatic breast cancer that had worsened with prior hormone therapy. Women were randomly assigned to treatment with palbociclib plus a standard hormone therapy (i.e., fulvestrant) or placebo plus fulvestrant. In the trial, the addition of palbociclib to hormone therapy nearly doubled the median time until the cancer worsened to 9.5 months, compared with 4.6 months with fulvestrant plus placebo. Approximately two-thirds of women experienced clinical benefit from the palbociclib regimen, and one-quarter experienced tumor shrinkage. The benefit of palbociclib was seen regardless of degree of hormone therapy resistance, hormone receptor level, and PIK3CA mutational status. However, the rates of severe adverse effects were substantially higher in the palbociclib group (73% v. 22%). The most common adverse effects were low blood counts (neutropenia, anemia, and leucopenia).
Palbociclib has also been studied as initial treatment for advanced breast cancer in combination with hormone therapy. In a large clinical trial, postmenopausal women with estrogen receptor (ER)–positive, HER2-negative breast cancer were treated with either letrozole plus placebo or letrozole plus palbociclib. Palbociclib extended the median time until the cancer worsened from 14 to 25 months in this study.56 The adverse effects among patients treated with palbociclib plus letrozole were similar to those seen previously with palbociclib in combination with fulvestrant (i.e., low blood counts, fatigue, and nausea).
In another clinical trial of first-line therapy for ER-positive, advanced breast cancer, patients were randomly assigned to receive letrozole plus placebo or letrozole plus ribociclib, a CDK4/6 inhibitor.57 In this trial, ribociclib markedly slowed cancer progression. After 18 months, cancer had not worsened in 63% of patients in the ribociclib group, compared with 42% of patients in the placebo group. The clinical outcomes and adverse effects for ribociclib and palbociclib seemed nearly identical.
It is not yet clear if palbociclib or ribociclib will extend overall survival because follow-up has not been sufficiently long nor have any biomarker tests been shown to predict who will or will not benefit from addition of these drugs. However, these findings have already changed the standard of care for patients with hormone receptor–positive metastatic breast cancer. The FDA approved palbociclib plus fulvestrant for women with disease progression after hormone therapy in February 2016.58 Palbociclib was previously approved for use with letrozole as initial hormone therapy for patients with ER-positive, HER2-negative advanced breast cancer.
Voices of Cancer Research: Rona Greenberg
Rona, a breast cancer survivor, had known that having a mutation in the BRCA2 gene increased her risk of other cancers. Still, it came as a shock when she was diagnosed with pancreatic cancer in 2015.
Since then, research advances have helped Rona survive. A targeted therapy called veliparib in combination with chemotherapy shrank the tumors for 10 months. While the treatment eventually stopped working, the potential of precision medicine leaves Rona and her doctor hopeful. She is now on another treatment that holds great promise.
Rona, pictured with her daughters, is a volunteer advocate with Facing Our Risk of Cancer Empowered (FORCE) and Letswinpc.org.
More effective treatments for advanced kidney cancer.
An estimated 62,700 adults were diagnosed with kidney cancer in the United States in 2016.59 Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults. At the time of diagnosis, nearly one-third of patients with RCC have metastatic cancer. The 5-year survival for people with metastatic RCC is only 12%. More information on kidney cancer can be found on Cancer.Net.
Advances in understanding kidney cancer biology led to the development of treatments targeting two molecular pathways: vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin (mTOR). Introduced approximately a decade ago, the treatments extend median survival for patients with advanced kidney cancer from 1 to 3 years. The current standard-of-care treatment for patients with recurrent, advanced kidney cancer includes VEGFR inhibitors axitinib and sorafenib and mTOR inhibitor everolimus.
In 2016, researchers reported findings from a large clinical trial suggesting an even more effective targeted treatment for relapsed RCC.60 Cabozantinib is an oral treatment that blocks several different targets in cancer cells, including tyrosine kinases MET, VEGFR2, and AXL. The median overall survival was 16.5 months in the group of patients treated with standard-of-care everolimus and 21.4 months in the group treated with cabozantinib. Patients who received cabozantinib had a 49% lower risk of cancer progression and substantially higher tumor shrinkage rates (17% v. 3%).
Severe-grade adverse effects that occurred more frequently with cabozantinib than with everolimus included high blood pressure, diarrhea, and fatigue. Anemia was more common in the everolimus group. On the basis of the findings from this study, the FDA approved cabozantinib in 2016 for the treatment of advanced RCC in patients who had received prior VEGFR inhibitor therapy.61
Two other large clinical trials explored VEGFR inhibitors in patients with advanced, nonmetastatic RCC who are at high risk of recurrence after surgery. Up to 40% of patients with stage III RCC experience a relapse with metastasis after kidney cancer surgery.62 There is currently no standard treatment for such patients, and the standard of care after surgery is surveillance.
In the S-TRAC (Sunitinib Treatment of Renal Adjuvant Cancer) trial, patients with stage III clear cell RCC were randomly assigned to treatment with sunitinib or placebo after surgery to remove the tumor.63 Sunitinib blocks VEGFR and several other molecular targets. The period until the cancer worsened was significantly longer in the sunitinib group (median, 6.8 years) than in the placebo group (median, 5.6 years). The rate of severe adverse effects, such as skin rash, high blood pressure, and fatigue, was higher in the sunitinib group than in the placebo group (63% v. 22%). Although these findings are encouraging, longer follow-up is needed to determine whether treatment with sunitinib in this setting prolongs survival.
In contrast, a much larger clinical trial, ASSURE (Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma; ECOG-ACRIN E2805), found no significant difference in the duration of disease-free survival between patients who received placebo (median, 6.6 years), sunitinib (median, 5.8 years), or sorafenib (median, 6.1 years) after surgery (this study was funded in part by a grant from the NCI).64 The most common severe adverse effects in the sunitinib and sorafenib groups were high blood pressure, hand-foot reaction, rash, and fatigue. Five deaths related to treatment occurred: one in the sorafenib group and four in the sunitinib group. The study authors concluded that neither sunitinib nor sorafenib should be used as adjuvant treatment for high-risk, advanced RCC.
Adjuvant VEGFR inhibitors should not be administered in the clinic until additional data are available to reconcile the differing results from the S-TRAC and ASSURE trials. A more compelling signal would be a trend toward survival benefit in either study, which currently does not exist. With multiple other adjuvant VEGFR studies underway, more data should be available to adjudicate the role of this treatment strategy. Physicians should continue to encourage enrollment of patients in ongoing trials that further explore the question.
A Policy Focus: Efforts Continue to Expand Access to Clinical Trials
ASCO continues to be concerned that only 3% of adult patients with cancer participate in clinical trials.1 This low participation rate not only limits patient access to new interventions that could treat, or even cure, their cancer, but also limits the knowledge gained from scientific inquiry to a small subset of patients.
ASCO submitted comments to the US Department of Health and Human Services and the National Institutes of Health on proposed rules aimed at increasing clinical trial participation and making clinical trial data more accessible and useful. The final rule, released in September 2016, requires researchers to register trials so that patients and their health care providers can more easily access trial information and determine if a patient is eligible to participate. In addition, researchers must also provide more detailed trial summary results, including information on adverse health events, on ClinicalTrials.gov.
Although this is a major step forward, more work is needed to expand access to clinical trials. Patients with low socioeconomic status, older adults, and ethnic and racial minority groups are under-represented in clinical trials. This impedes our ability to make progress against cancer in the populations who experience disparities in access to cancer care and treatment outcomes. ASCO continues to work with policymakers to expand access to clinical trials by relaxing overly restrictive eligibility requirements and by requiring Medicaid to cover routine costs of care for clinical trial participants. ASCO also worked with the American Association of Cancer Institutes through the Best Practices in Cancer Clinical Trials Initiative to develop and promote practical solutions to meet administrative and regulatory requirements in clinical cancer research.
1 Institute of Medicine Forum on Drug Discovery, Development, and Translation: Transforming Clinical Research in the United States: Challenges and Opportunities: Workshop Summary. Washington, DC, National Academies Press, 2010
Promising treatment for ovarian cancer.
With survival in the range of 12 to 18 months, women with recurrent ovarian cancer are in desperate need of better therapies. Research findings reported in 2016 may lead to a new approach to treat this difficult cancer.65 In an early-stage clinical trial, four of 10 women with folate receptor alpha–positive ovarian cancer resistant to standard platinum chemotherapy experienced tumor shrinkage after receiving IMGN853 (mirvetuximab soravtansine). The most common adverse effects were diarrhea, eye problems, cough, fatigue, and decreased appetite.
IMGN853 belongs to the new class of cancer therapies known as ADCs. It comprises an antibody targeting folate receptor alpha (a marker found in most ovarian cancers) and a potent anticancer drug called DM4, which blocks cell division and growth. Additional clinical trials of IMGN853 in women with folate receptor alpha–positive ovarian cancer are already underway (ClinicalTrials.gov identifiers: NCT02631876 and NCT02606305).
Combined Modality Therapy
It is common that patients with cancer receive two or more treatments at a time, at least at some point during the course of their illness. Such common modality therapies can work better than standalone treatments, but this improved efficacy often comes with more adverse effects. As with all new approaches, before any new combination of treatments becomes part of routine care, its benefits and safety need to be evaluated in a clinical trial against a standard treatment regimen. Last year, clinical trials delivered important advances in combined modality therapies for brain cancer, neuroblastoma, and colorectal cancer.
Adding chemotherapy to radiation therapy extends glioma survival.
In 2016, scientists reported long-awaited results from a federally funded clinical trial of patients with grade 2 glioma (this study was funded by a grant from the NCI).66 Grade 2 gliomas are rare, accounting for only 5% to 10% of all brain tumors, and often occur in younger people. Although low-grade gliomas grow slower than other types of brain cancer, they lead to worsening neurologic symptoms and often premature death.
In the study, patients were randomly assigned to receive radiation therapy alone or radiation therapy followed by PCV (procarbazine, CCNU, and vincristine) chemotherapy. The median survival was substantially longer among patients treated with chemotherapy and radiation therapy (13.3 years) than among those who received radiation therapy alone (7.8 years). Addition of chemotherapy also slowed the course of the disease; at 10 years, the cancer worsened in only 21% of patients in this group. In contrast, cancer worsened in 51% of patients treated with radiation therapy alone. This study led to a change in the standard of care for high-risk, low-grade gliomas; PCV chemotherapy is now added to radiation therapy.
More effective regimen for children with high-risk neuroblastoma.
Neuroblastoma is the second most common solid tumor in children and the most common cancer in infancy. It begins in nerve cells outside of the brain. Approximately 700 children are diagnosed with neuroblastoma each year in the United States, most younger than age 6 years. High-risk neuroblastoma requires intensive treatment, which may include surgery, chemotherapy, radiation therapy, and/or autologous stem cell transplant (ASCT). Despite all these treatments, fewer than half of children will survive 5 years after diagnosis of a high-risk neuroblastoma.
A federally funded trial performed by the Children’s Oncology Group found that adding a second autologous stem cell transplant or ASCT to standard therapy can improve patient outcomes (this study was funded in part by a grant from the NCI).67 At 3 years, cancer had not recurred in 61% of patients who had undergone two transplantations, compared with 48% of patients who had undergone one.
The 3-year survival rate was slightly higher in the double transplantation group than in the single transplantation group (74% v. 69%), but this difference was not statistically significant. This study was not designed to observe a difference in overall survival between the two treatment groups. However, given that most neuroblastoma recurrences occur within 2 to 3 years of diagnosis, patients who had not experienced a recurrence at 3 years had a better chance of long-term survival.
The rates of severe adverse effects, such as infections and liver problems, were similar between the two treatment groups, although fewer treatment-related deaths occurred with double transplantation. Nonetheless, it is important to keep in mind that the combination therapy for high-risk neuroblastoma is one of the most aggressive cancer regimens administered to children. Longer patient follow-up is needed to determine if there are any long-term or late-onset adverse effects of this therapy.
Colon tumor location: a factor to consider in treatment decisions.
An unexpected factor may help explain why some patients with colorectal cancer do better than others. According to an analysis of data from a large clinical trial, patients with advanced colorectal cancer live longer if the cancer begins on the left side of the colon rather than on the right side (this study was funded in part by a grant from the NCI).68 In the trial, patients received a combination of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or FOLFIRI (fluorouracil, leucovorin, and irinotecan) chemotherapy with either of the two standard targeted therapies for advanced colorectal cancer: cetuximab or bevacizumab. In prior research, the two treatments yielded similar survival. In this analysis, the median survival for patients with left-sided tumors was 33 months, but it was only 19 months for those with right-sided tumors.
A separate analysis of data from two other clinical trials also found that patients with advanced colorectal cancer that began on the left side of the colon lived longer than those with cancers that began on the right side.69 Among patients with left-sided tumors, the combination of cetuximab and FOLFIRI was more effective than bevacizumab and FOLFIRI, whereas patients with right-sided tumors experienced limited benefit from either regimen.
For now, the compelling findings from these studies suggest that clinicians should take into account the location of the primary tumor when making treatment decisions for patients with advanced colorectal cancer. For patients with a right-sided colorectal cancer, cetuximab may not provide a benefit. However, for those patients whose tumors originate in the left colon, either a bevacizumab- or cetuximab-based regimen is effective, with cetuximab seeming to produce the best outcomes when combined with chemotherapy.
Finally, an analysis of pooled data from 66 clinical trials and more than 1.4 million patients revealed that left-sided primary colon tumors were associated with a better prognosis than right-sided tumors, irrespective of cancer stage.70 Overall, patients with left-sided tumors had a 20% lower risk of death. This analysis suggests that the location of primary tumor should be considered when establishing prognosis and designing future clinical trials in both early and advanced colorectal cancers.
Even in the era of precision medicine, chemotherapy remains a key treatment modality for many patients with cancer. Along with development of new chemotherapies, researchers are exploring new ways to use conventional chemotherapies. The past year brought important advances in chemotherapy for treatment of patients with pancreatic cancer and leukemia.
Pancreatic cancer: two-drug regimen increases chance of living longer.
Pancreatic cancer is often difficult to diagnose. As a result, it is often not found until it has spread from the pancreas to other parts of the body and can no longer be removed with surgery. Overall, only 29% of patients with pancreatic cancer will be alive 1 year after diagnosis. As the fourth leading cause of death resulting from cancer in the United States, pancreatic cancer took an estimated 42,000 lives in 2016.71
Patients who are diagnosed early enough for surgical removal of the tumor have a chance of longer survival. For the past two decades, the standard of care after pancreatic cancer surgery has been gemcitabine chemotherapy, which is administered to eliminate remaining cancer cells and reduce the chance of relapse. However, the benefit of gemcitabine is relatively modest, with only 20% of patients surviving 5 years.
A recent clinical trial found that adding a second chemotherapy drug, capecitabine, to gemcitabine can help such patients live even longer.72 The median survival was 28 months in the group of patients treated with the two-drug regimen and 25.5 months in the group that received gemcitabine alone. Despite a small difference in median survival, addition of capecitabine increased the chance of surviving 5 years from 16% to 29%.
These results have set a new standard of care for use of gemcitabine plus capecitabine as adjuvant (postsurgery) therapy after pancreatic cancer surgery. Gemcitabine and capecitabine are both FDA approved for use in several different cancers and are available as generic medicines.
The combination regimen was well tolerated overall, with no significant increase in adverse effects compared with gemcitabine alone. The safety of the gemcitabine–capecitabine combination allows for the possibility of adding other treatments to this regimen with the goal of further improving patient benefit.
High-risk AML: new packaging of conventional drugs extends survival.
With current therapy, people with AML live only approximately 6 months after diagnosis. There has been little improvement in AML survival in the last few decades, but last year brought not only a promising new targeted therapy (described under Targeted Therapy), but also an improved chemotherapy regimen.73
The new medicine, called CPX-351, packs cytarabine and daunorubicin into a liposome, which helps the chemotherapy slip into leukemia cells. CPX-351 was investigated in a late-stage clinical trial of older patients newly diagnosed with secondary AML. Secondary AML can develop as a result of treatment of another cancer or environmental exposure to radiation or certain chemicals.
In the study, patients who received CPX-351 lived approximately 4 months longer (median survival, 10 months) than those who received standard combination chemotherapy (median survival, 6 months) with the same drugs. At 2 years, 31% of patients were alive in the CPX-351 group versus 12% of patients in the standard chemotherapy group. There were no differences in adverse effects between the two groups of patients.
These findings represent a long-awaited advance in treatment of older adults with high-risk or secondary AML. The FDA has granted CPX-351 a breakthrough therapy designation for treatment of patients with AML.
New Concerns About Laparoscopic Rectal Cancer Surgery
In recent years, laparoscopic surgery has emerged as an attractive alternative to the traditional open surgery because of its shorter recovery time and lower rate of complications. The procedure is performed with the aid of a video camera and instruments inserted through small incisions in the abdomen.
Patients with early and locally advanced rectal cancer can be cured with surgery, provided the tumor tissue is completely removed. However, the choice between open and laparoscopic surgery is not easy to make for such patients. Experts have raised concerns that laparoscopic surgery may not remove tumor tissue as completely as open surgery does. As a result, patients who undergo laparoscopic surgery may have a greater chance of cancer recurrence and consequently shorter survival.
In one recent clinical trial, rates of surgical success (i.e., complete tumor removal) were found to be substantially lower among patients with rectal cancer who underwent laparoscopic surgery than among those who underwent open surgery (82% v. 87%).74 Similar trends were seen in another large trial, where successful surgery was achieved in 82% of patients undergoing a laparoscopic procedure and 89% of patients undergoing open surgery.75
These findings confirm concerns that laparoscopic surgery may lead to more cancer recurrences and shorter survival. Patients enrolled in these two trials will continue to be observed to answer this question. Meanwhile, routine use of laparoscopic surgery is not recommended for patients with stage II or III rectal cancer. In contrast, laparoscopic surgery is a well-accepted procedure for patients with colon cancer.
A Policy Focus: Robust Federal Funding Needed for Cancer Research Progress
ASCO continues to urge legislators to make a robust national investment in medical research through the National Institutes of Health (NIH) and the National Cancer Institute.
For much of the past decade, federal funding for biomedical research has been flat, and in inflation-adjusted dollars, the NIH budget was 20% lower in 2016 than it was a decade before.1 This dramatic drop in funding limits the ability of scientists to conduct important research that advances the prevention, diagnosis, and treatment of cancer for millions of people.
Even under tight budgetary constraints, Congress must provide consistent and predictable funding increases to continue our momentum to prevent cancer and improve cancer treatment for patients.
1 National Institutes of Health: Appropriations.
Longer Hormone Therapy Further Reduces Breast Cancer Recurrence
Breast cancer can recur many years after a woman completes treatment for early-stage, hormone receptor–positive breast cancer. To lower the chance of recurrence, many women receive hormone therapy after surgery. In 2016, researchers reported that extending a form of hormone therapy called aromatase inhibitors from the standard 5 years to 10 years may further reduce the risk of recurrence.76
The study enrolled postmenopausal women with early breast cancer who had completed 5 years of aromatase inhibitor hormone therapy either as first-line treatment or after tamoxifen. The women were randomly assigned to receive the aromatase inhibitor letrozole for 5 additional years or placebo.
The chance of breast cancer recurrence or development of a second cancer in the opposite breast was 34% lower in the letrozole group than in the placebo group. At 5 years of follow-up, 95% of women in the letrozole group and 91% of women in the placebo group remained breast cancer free. The rates of second breast cancers were lower in the letrozole group (0.2% v. 0.5%). Nonetheless, 5-year survival rates were not significantly different between the two groups (letrozole, 94% v. placebo, 93%).
Adverse effects of hormone therapy can be difficult to bear, particularly over a long period of time. Although bone pain, fractures, and osteoporosis occurred more frequently with letrozole than with placebo, researchers found no significant differences in either overall quality of life or menopause-specific symptoms.
Furthermore, a separate analysis of more than 45,000 patients who were observed for 15 years after receiving 5 years of hormone therapy provides a more accurate estimate of the risk of breast cancer recurrence according to initial tumor stage, grade, and lymph node status.77 The findings will help inform decisions about continuing hormone therapy beyond 5 years.
These findings are important to millions of women around the world who receive a diagnosis of hormone receptor–positive breast cancer each year. They provide much-needed direction to physicians and patients discussing whether to extend hormone therapy beyond the previous standard of 5 years, particularly in women who found the first 5 years of treatment acceptable.
Recent Clinical Practice Guidelines
Clinical practice guidelines help distill knowledge about a particular clinical issue and provide recommendations to help clinicians deliver the best treatment and care to every patient. ASCO develops its clinical practice guidelines through a rigorous, systematic review of relevant medical literature and clinical interpretation from a multidisciplinary panel of experts and patient representatives. In 2016, ASCO issued more than 17 new clinical practice guidelines, updates, adaptations, and endorsements (Appendix, Table A2).
For additional notable advances in cancer treatment, please see Appendix Table A1.