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Sunday, June 3, 2018

Rise in lifestyle-related cancers over past decade spotlights need for prevention


Lifestyle-related cancers, such as lung, colorectal, and skin cancers, have increased globally over the past decade, according to the most comprehensive analysis of cancer-related health outcomes and patterns ever conducted.
“While the increase in lung, colorectal, and skin cancers over the past decade is concerning, the prevention potential is substantial,” said Dr. Christina Fitzmaurice, Assistant Professor of Global Health at the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, whose organization coordinated the study. “Vital prevention efforts such as tobacco control, dietary interventions, and broader health promotion campaigns need to be scaled up in response to this rise in lifestyle-related cancers.”
The study, published today in JAMA Oncology, covers 1990 to 2016; it is part of the Global Burden of Disease (GBD) study, a comprehensive effort to quantify health internationally. Researchers reviewed 29  groups, including lung, breast, prostate, skin, colorectal, pancreatic, stomach, and liver cancers, as well as leukemia and other cancer groups (full list below). The study provides findings by age and sex for 195 countries and territories.
While lifestyle-related cancers saw a universal increase from 2006 to 2016, several cancers from infectious causes—including cervical and stomach cancers—decreased over the same time period.
Study estimates were analyzed using a Socio-demographic Index (SDI) based on rates of education, fertility, and income. SDI is more comprehensive than the historical “developed” versus “developing” nations framework. Countries with high SDI have high levels of income and education and low fertility, whereas low-SDI countries have low levels of income and education and high fertility.
Large disparities in  and death persist between high- and low-SDI countries. Researchers found rates of cancer incidence and death remained higher in high-SDI countries in 2016. For example, the odds of developing  over the course of one’s lifetime were the highest—at 1 in 10 women—in high-SDI countries, but only 1 in 50 for women in low-SDI countries.
Conversely, the largest and fastest increase in new cancer cases between 2006 and 2016 occurred in middle-SDI countries. And women in low-SDI countries are nearly four times more likely to develop cervical cancer than women in high-SDI countries, and in 2016,  was the most common cause of cancer incidence and death in low-SDI countries.
“Ensuring universal access to health care is a vital prerequisite for early detection and cancer treatment,” said Fitzmaurice. “And improving access to advanced diagnostic technologies not commonly available in low-SDI countries is a critical step toward achieving health equity globally.”
Additional key findings include:
  • In 2016, there were 17.2 million cancer cases worldwide, an increase of 28% over the past decade. There were 8.9 million cancer deaths the same year.
  • While cancer death rates decreased in a majority of countries from 2006 to 2016, incidence rates conversely increased.
  • Breast cancer was the leading cause of cancer death in women.
  • Lung cancer was the leading cause of cancer death in men; it was also the leading cause of cancer mortality globally, accounting for nearly 20 percent of all cancer deaths in 2016.
  • Prostate cancer is one of the most common causes of cancer incidence and death in men, in both high- and low-SDI countries, but especially in sub-Saharan Africa.
NEW CASES PER 100,000 PEOPLE (AGE-ADJUSTED), 2016″Worst” and “best” countries and global
  1. Tracheal, bronchus, and lung cancer: North Korea (56.9), Kenya (4.2), global (30.2)
  2. Colon and rectum cancer: Netherlands (57.5), The Gambia (4.3), global (25.9)
  3. Breast cancer: Luxembourg (61.8), Niger (5.8), global (24.1)
  4. Non-melanoma skin cancer: Australia (300.4), Bangladesh (0.7), global (23.2)
  5. Prostate cancer: Dominica (113.1), North Korea (2.4), global (22.1)
  6. Stomach cancer: South Korea (44.5), Namibia (2.7), global (17.3)
  7. Liver cancer: Mongolia (108.4), Morocco (1.9), global (14.6)
  8. Other neoplasms: Malawi (39.6), Syria (2.6), global (10.9)
  9. Cervical cancer: Somalia (34.0), Qatar (1.1), global (7.0)
  10. Leukemia: New Zealand (20.3), Zambia (2.0), global (6.8)
  11. Non-Hodgkin lymphoma: Canada (21.2), Kyrgyzstan (1.5), global (6.7)
  12. Bladder cancer: Lebanon (31.1), Nigeria (1.2), global (6.7)
  13. Esophageal cancer: Malawi (25.2), Syria (0.7), global (6.6)
  14. Pancreatic cancer: Czech Republic (12.5), India (2.6), global (6.4)
  15. Uterine cancer: Latvia (23.1), Bangladesh (0.8), global (6.0)
  16. Lip and oral cavity cancer: Pakistan (22.1), Sao Tome and Principe (1.0), global (5.5)
  17. Kidney cancer: Latvia (20.5), Nepal (1.0), global (5.0)
  18. Brain and nervous system cancer: Iceland (20.8), Namibia (1.4), global (4.6)
  19. Malignant skin melanoma: Australia (55.6), Nepal (0.2), global (4.1)
  20. Ovarian cancer: Estonia (9.3), Niger (1.2), global (3.6)
  21. Thyroid cancer: Iceland (18.7), Ghana (0.2), global (3.3)
  22. Gallbladder and : Chile (11.5), Uzbekistan (0.6), global (2.8)
  23. Larynx cancer: Cuba (8.8), The Gambia (0.6), global (2.7)
  24. Other pharynx cancer: Hungary (7.3), Palestine (0.2), global (2.4)
  25. Multiple myeloma: Barbados (6.3), Tajikistan (0.4), global (2.1)
  26. Nasopharynx cancer: Malaysia (5.1), Mali (0.1), global (1.3)
  27. Hodgkin lymphoma: Greece (5.3), Syria (0.1), global (1.0)
  28. Testicular cancer: Chile (6.4), Mozambique (0.04), global (0.9)
  29. Mesothelioma: United Kingdom (2.9), Palestine (0.1), global (0.5)
DEATHS PER 100,000 PEOPLE (AGE-ADJUSTED) IN 2016 “Worst,” and “best” countries and global
  1. Tracheal, bronchus, and lung cancer: North Korea (61.7), Egypt (4.8), global (25.8)
  2. Colon and rectum cancer: Hungary (31.3), Sri Lanka (5.0), global (12.8)
  3. Stomach cancer: Mongolia (44.0), Maldives (3.2), global (12.6)
  4. Liver cancer: Mongolia (114.7), Morocco (2.0), global (12.1)
  5. Breast cancer: Tonga (24.7), Oman (4.0), global (7.9)
  6. Other neoplasms: Malawi (37.6), Syria (2.6), global (6.4)
  7. Esophageal cancer: Malawi (32.4), Syria (0.8), global (6.2)
  8. Pancreatic cancer: Uruguay (12.8), Bangladesh (2.5), global (6.2)
  9. Prostate cancer: Dominica (54.9), North Korea (1.9), global (6.1)
  10. Leukemia: Syria (15.3), Bangladesh (1.9), global (4.6)
  11. Non-Hodgkin lymphoma: Grenada (11.0), Kyrgyzstan (1.4), global (3.6)
  12. Cervical cancer: Zimbabwe (28.7), Syria (0.6), global (3.5)
  13. Brain and nervous system cancer: Palestine (8.3), Japan (1.2), global (3.2)
  14. Bladder cancer: Malawi (11.8), Albania (0.9), global (2.9)
  15. Lip oral cavity cancer: Kiribati (14.6), Syria (0.6), global (2.6)
  16. Gallbladder and biliary tract cancer: Chile (11.3), Uzbekistan (0.6), global (2.5)
  17. Ovarian cancer: Lithuania (5.9), United Arab Emirates (0.9), global (2.4)
  18. Kidney cancer: Czech Republic (7.1), Bangladesh (0.5), global (2.0)
  19. Other pharynx cancer: India (6.1), Syria (0.2), global (1.7)
  20. Larynx cancer: Cuba (5.3), Japan (0.4), global (1.6)
  21. Multiple myeloma: Dominica (5.9), Tajikistan (0.4), global (1.5)
  22. Uterine cancer: Grenada (5.4), Maldives (0.5), global (1.3)
  23. Malignant skin melanoma: New Zealand (6.6), Bangladesh (0.2), global (0.9)
  24. Nasopharynx cancer: Malaysia (3.7), Chile (0.1), global (0.9)
  25. Non-melanoma skin cancer: Zimbabwe (4.5), Bangladesh (0.2) global (0.8)
  26. Thyroid cancer: Zimbabwe (2.3), Syria (0.2), global (0.6)
  27. Mesothelioma: United Kingdom (2.6), Palestine (0.1), global (0.5)
  28. Hodgkin lymphoma: Afghanistan (2.2), Japan (0.1), global (0.4)
  29. Testicular cancer: Kiribati (1.0), Maldives (0.02), global (0.1)
NEW CANCER CASES PER 100,000 PEOPLE (AGE-ADJUSTED) IN 2016
Highest rates
  1. Australia (743.8)
  2. New Zealand (542.8)
  3. United States (532.9)
  4. Netherlands (477.3)
  5. Luxembourg (455.4)
  6. Iceland (455.0)
  7. Norway (446.1)
  8. United Kingdom (438.6)
  9. Ireland (429.7)
  10. Denmark (421.7)
Lowest rates
  1. Syria (85.0)
  2. Bhutan (86.0)
  3. Algeria (86.7)
  4. Nepal (90.7)
  5. Oman (94.9)
  6. Maldives (101.3)
  7. Sri Lanka (101.6)
  8. Niger (102.3)
  9. Timor-Leste (105.9)
  10. India (106.6)
CANCER DEATHS PER 100,000 PEOPLE (AGE-ADJUSTED) IN 2016
Highest rates
  1. Mongolia (272.1)
  2. Zimbabwe (245.8)
  3. Dominica (203.1)
  4. Hungary (202.7)
  5. Grenada (201.0)
  6. Uruguay (190.6)
  7. Tonga (189.7)
  8. North Korea (188.7)
  9. Saint Vincent and the Grenadines (183.1)
  10. Croatia (180.2)
Lowest rates
  1. Syria (67.4)
  2. Algeria (67.5)
  3. Oman (69.2)
  4. Maldives (72.0)
  5. Sri Lanka (74.7)
  6. Bhutan (78.6)
  7. Uzbekistan (80.6)
  8. Nicaragua (80.9)
  9. Morocco (81.0)
  10. Qatar (81.6)
 Explore further: Study estimates global cancer cases, deaths in 2015
More information: Global Burden of Disease Cancer Collaboration, Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016, JAMA Oncology (2018). DOI: 10.1001/jamaoncol.2018.2706
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#ASCO18: Targeted cancer treatments far outperform traditional methods


Cancer treatments that attack tumors based on their individual genetic traits—not their location in the body—far outperform traditional methods, extending survival for twice as many patients, a study said Saturday.
The precision medicine field of targeted therapy involves testing tumors for clues about their genetic mutations, and matching patients with new drugs designed to block cancer’s growth on a molecular level.
Targeted options for patients have risen dramatically in the last two decades—and one day tumor testing and cell-free DNA analysis may become the standard of care, said lead investigator Apostolia Tsimberidou, professor of investigational cancer therapeutics at MD Anderson Cancer Center in Texas.
“I am optimistic that in the next few years we will dramatically improve the outcomes of patients with cancer with increasing implementation of precision medicine,” she told reporters at the American Society of Clinical Oncology meeting in Chicago, the world’s largest annual cancer conference.
Tsimberidou and colleagues began studying the impact of these therapies in 2007, after seeing the success of Gleevec (imatinib)—a breakthrough drug approved by US regulators in 2001 that showed huge success against .
Their study, called IMPACT, is the first and largest to look at survival across a host of cancer types and many different targeted therapies.
More than 3,700 patients at Texas MD Anderson Cancer Center enrolled from 2007 to 2013.
All had advanced cancers, or “end-stage disease,” involving cancers of the gastrointestinal tract, breast, or lung. Melanoma and cancer of the female reproductive tract were also included, along with more rare types of cancer.
Those enrolled had typically tried at least four—and sometimes up to 16—other treatments that failed to halt the growth of their cancer.
More than 1,300 were found to have tumors with at least one genetic change. Of these, 711 received a treatment that matched the biology of the tumor. Another 596 received a treatment was not matched, often because no matched treatment for the patient was available at the time.
After three years, 15 percent of people treated with targeted cancer therapies were alive, compared to seven percent in the non-targeted group.
After 10 years, six percent of the targeted group was alive, compared to just one percent in the other group.
Still far from a cure
On the whole, targeted therapies led to an average of four months of life without the cancer advancing, known as progression-free survival, and nine extra months of overall survival.
Those who were treated with traditional approaches lived just under three months without cancer growing, and 7.3 months longer overall.
Targeted therapies “significantly improved overall survival,” said Catherine Diefenbach, an oncologist at New York University (NYU) Langone.
This method of molecularly profiling tumors, understanding their genetics and how to act on that “is the wave of the future,” added Diefenbach, who was not involved in the study.
For Diefenbach, the study illustrates a paradigm shift in cancer treatment, whereby cancers are no longer treated on the “neighborhood” of the body in which they arise.
“Prior to precision medicine, patients were treated based on what kind of cancer they had,” she told reporters.
“But a breast cancer patient, as we have heard, can have a cell that is much more like a lung cancer patient, genetically, than another breast .”
Diefenbach also pointed out that “most of these patients received drugs that were already (US Food and Drug Administration) FDA-approved or in advanced clinical trials, so people did not have to go out and reinvent the wheel to treat these patients in a completely new way.”
The field of  has grown immensely since the study began, said Tsimberidou, recalling that back in 2007, “we tested for no more than one to two genes.
“Now patients are being tested for hundreds of actionable genes, amplifications and mutations, as well as for immune markers,” she said.
 Explore further: Precision oncology in advanced cancer patients improves overall survival
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How Not Working At Trading Can Help Your Trading


Think of working out in the gym.  There is time when you work the muscles, and there is time when you rest them.  The cycle of workout and rest increases blood flow to those muscles and enables them to grow in a sustainable fashion.  If you only rested, you would never build your muscles.  If you only worked, you would overtax yourself and break yourself down.  Growth occurs over multiple cycles of work and rest.
This is an important lesson of the Sabbath in the world’s religious traditions.  After a period of creation, we rest and renew.
Some traders fail because they work too hard.  Others fail because they hardly work.  Performance is achieved when we effectively alternate effort and renewal.  Growth occurs in the cycles of doing and reflecting that comprise deliberate practice.
Thanks to a savvy portfolio manager who passed along this article on how the Golden State Warriors make use of their halftime to dominate the third quarter of their games.  It is fascinating to see how the coaches plan for the halftime during the game, collecting videos that will help the team build their confidence and focus on the right things in the second half.  The period of rest during halftime becomes an integral part of improved performance for the remainder of the game.
Mike Bellafiore, in a recent blog post, notes that this same dynamic occurs on the trading floor.  Traders keep running “playbooks” of their best trades and use breaks during the trading day to review their plays and share insights with other traders.  When I worked at Kingstree in Chicago, traders would formally divide their trading day into morning and afternoon sessions, with a break in between.  They allocated separate risk (loss limits) to the two sessions, effectively creating two trading “days” in one.   Midday served as a halftime, a period of rest when they could learn from what they did right and wrong, update market views, share insights with colleagues, and rejuvenate.
What are your halftime drills?  How are you utilizing periods of rest in your trading?  In your life?
When we increase the frequency of cycles between “performance” and “halftime”, we speed our deliberate practice and development.
How we rest is as important as how we work.
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Clovis, Immunomedics to collaborate on cancer combo med


Clovis Oncology (CLVS) and Immunomedics (IMMU) announced their intent to enter into a clinical collaboration to investigate the combination of Clovis’ Rubraca, a poly polymerase inhibitor, and Immunomedics’ lead antibody-drug conjugate product candidate, sacituzumab govitecan, as a treatment of patients with metastatic triple-negative breast cancer and metastatic urothelial cancer. The planned phase 1/2 study will include an initial safety cohort followed by expansion cohorts in each of mTNBC and mUC. In preclinical studies, the combination of sacituzumab govitecan and rucaparib in TNBC cell lines in vitro resulted in synergistic growth inhibition regardless of BRCA1/2 status. In addition, the combination of sacituzumab govitecan and a PARPi also demonstrated significant antitumor effects above that observed with monotherapy in BRCA wild-type and mutant animal models of TNBC.
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#ASCO18: Maintenance Therapy Changes Paradigm in Rare Childhood Sarcoma


Practice-changing findings were reported for pediatric rhabdomyosarcoma at the 2018 ASCO Annual Meeting Sunday. Investigators said a course of low-dose maintenance chemotherapy administered after standard-of-care intensive chemotherapy led to significant improvements in disease-free (DFS) and overall survival (OS).
The findings from the decade-long trial were hailed as 1 of the 4 most important clinical developments to emerge from the 5800 abstract presentations at the ASCO meeting.
Patients receiving maintenance therapy had a 5-year DFS advantage of 77.6% versus 69.8% in the standard arm (HR = 0.68; 95% CI, 0.45-1.02; P = .0613). Low-dose maintenance therapy following initial treatment increased the 5-year OS from 73.7% to 86.5% in pediatric cases (HR = 0.52; 95% CI, 0.32-0.86; P = .0111).1,2
“At the end of this long, but not easy, study, we concluded that maintenance is an effective and well-tolerated treatment for children with high risk rhabdomyosarcoma and our group decided this is the new standard treatment for patients—at least, in Europe we will keep standard intensive chemotherapy and then we’ll continue with 6 more months of low-dose chemotherapy,” said lead study author Gianni Bisogno, MD, PhD, a professor at the University Hospital of Padova in Italy and Chair of the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG).
Bisogno added that this maintenance approach can potentially be applied to other pediatric tumors.
The standard intensive therapy course is a 6- to 8-month regimen that includes 9 cycles of high-dose chemotherapy, radiotherapy, and surgery. Patients up to the age of 21 with no evidence of metastasis were enrolled in the study following standard treatment, and were randomized to either stop treatment or continue with maintenance therapy for 6 additional months. Treatment in the experimental arm included 6 cycles of intravenous vinorelbine at 25 mg/m2 on days 1, 8, and 15 of each 28-day cycle; and continuous daily oral cyclophosphamide at 25 mg/m2. Standard treatment included 9 cycles of ifosfamide, vincristine, and actinomycin D, plus or minus doxorubicin, surgery, and/or radiotherapy.
Those enrolled were considered at high risk of recurrence due to having large tumors in hard-to-treat locations. After completing standard treatment, 371 patients aged 6 months to 21 years (79% 10 years or younger) were randomized to standard (n = 186) or maintenance care (n = 185).
In addition to prolonged survival rates, there were no cardiac, hepatic, gastrointestinal, or renal toxicities. “Treatment toxicities were much lower in comparison with what we usually see with standard chemotherapy,” Bisogno said. ‘We have less anemia, less neutropenia, less thrombocytopenia. We had fewer episodes of infection and we didn’t see any important organ dysfunction.”
Low blood cell counts were the most common adverse event in the maintenance arm, although generally mild. Febrile neutropenia occurred in 25% of patients, and infections were lower in the maintenance arm (29.4%) than what is generally seen with standard therapy. Grade 4 neurotoxicity occurred in 1.1% of patients.
Grade 3/4 hematological toxicities in the maintenance arm included neutropenia (80.6%), leukopenia (73.9%), anemia (8.9%), and low platelet counts (0.6%).
Rhabdomyosarcoma is a rare soft tissue cancer that is diagnosed in 350 children in the United states and 320 in the European Union each year; 40% of all rhabdomyosarcoma diagnoses occur in adults. Modern treatment enables the cure of 70% to 80% of children, and children who are alive at 5 years are considered cured, as recurrence is low.
However, standard of care in this disease has not changed in 30 years, Bisogno said.
“At the end of standard treatment more than 90% of children have no evidence of tumor, but we know that after 1 year or 2 years, one-third of these children relapse and most of them die,” Bisogno said, explaining the decision to initiate the trial of maintenance therapy.
ASCO expert Warren Chow, MD, a specialist in the treatment of sarcomas, described the EpSSG study as a model for how to conduct large and important trials in rare diseases. The trial took 10 years to complete partly because of the rarity of the disease and the challenges in reaching the enrollment goal.
Because there are slight differences in the way rhabdomyosarcoma is treated in the United States, there will need to be further tests with US protocols before these new findings become standard of care, Chow said. Also, it will need to be determined whether these results are applicable to patients older than 21 years of age, he said. “Even with these caveats, this is the most significant treatment advance in this disease in more than 30 years.”

References

  1. Bisogno G, Luca De Salvo G, Bergeron C, et al. Maintenance low-dose chemotherapy in patients with high-risk (HR) rhabdomyosarcoma (RMS): A report from the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG). J Clin Oncol. 2018;36(suppl;abstr LBA2).
  2. Maintenance Chemotherapy Extends Life for Children With a Rare Cancer – First Treatment Advance for This Cancer in 30 Years [press release]. Alexandria, VA: ASCO; June 3, 2018. https://www.asco.org/about-asco/press-center/news-releases/maintenance-chemotherapy-extends-life-children-rare-cancer?et_cid=40339664&et_rid=513052853&linkid=Read+more
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#ASCO18: Agios med induces deep remission in leukemia in Phase 1


Single-agent ivosidenib was well tolerated and resulted in deep and durable remissions in patients with relapsed or refractory acute myeloma leukemia (AML) who harbor an isocitrate dehydrogenase-1 (IDH1) mutation, according to a researcher here.
The rate of complete remission (CR) or CR with partial hematologic recovery (CRh) was 30.4% in these patients (95% CI, 22.5-39.3), reported Daniel Pollyea, MD, of the University of Colorado School of Medicine in Aurora, at the American Society of Clinical Oncology (ASCO) annual meeting.
“In this population of IDH-positive relapsed/refractory AML patients, ivosidenib was able to achieve durable responses,” said Pollyea.
The true CR rate with ivosidenib (formerly AG-120) was 21.6%, with a median duration of response of 9.3 months (95% CI, 5.6-18.3) and median overall survival (OS) of 18.8 months in these patients.
In all, 41.6% of patients responded (95% CI, 32.9-50.8), with a 6.5-month median duration of response (95% CI, 4.6-9.3), according to the study, which was published simultaneously in the New England Journal of Medicine.
“In addition, patients were able to achieve transfusion independence,” Pollyea said. Among 84 patients dependent on either red-cell or platelet transfusions (or both) at the start of treatment, 35% attained transfusion independence — and fewer infectious complications were seen in these patients.
Daniel Pollyea, MD
Daniel Pollyea, MD, presenting the results
Of the 41 patients who were transfusion-independent at the start of treatment, more than half were able to maintain this for 56 days or more while on treatment.
In February 2018, the FDA accepted a New Drug Application (NDA), along with priority review, for ivosidenib for the treatment of patients with relapsed or refractory AML with IDH1 mutation. The agency is expected to make their decision later this year.
Following similar phase I data last year, the FDA approved the oral IDH2 inhibitor enasidenib (Idhifa) for relapsed or refractory AML patients with IDH2 mutations.
ASCO discussant Eunice Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, described ivosidenib as a “companion drug” for patients with IDH1-mutations.
IDH1 mutations are more rare than IDH2 mutations, occurring in roughly 6%-10% of AML patients compared with 9%-13%.
Wang told MedPage Today that like enasidenib for IDH2-mutant AML, ivosidenib will likely become the next standard of care in IDH1-mutant AML. “I can’t imagine the FDA would not approve the drug given the similarity of the data,” she said, adding that AML patients will need to routinely be tested for IDH1/IDH2 mutations.
“I am hopeful that we’ll have approval of AG-120, or ivosidenib, before the summer is out,” said study co-author Courtney DiNardo, of MD Anderson Cancer Center in Houston.
In the clinic, DiNardo told MedPage Today that she has seen “dramatic” responses to the drug firsthand, noting two patients she treated on the study who had durable responses of 1 to 2 years.
But Wang highlighted that more work needs to be done, citing the need for markers of resistance, whether they be co-mutations or otherwise. The study tested for the variant allele frequency of IDH1 mutations, and in 21% of CR/CRh patients, no residual IDH1mutations were detectable on digital polymerase-chain-reaction assay. “So the drug is working, but we’re not seeing massive eradication of that molecular marker,” she said.
Eunice Wang, MD
Eunice Wang, MD, discussing the results
The next generation of IDH1 inhibitors, some of which are already undergoing dose-escalation studies, may be the solution to move treatment forward for these patients, Wang said.
The current study looked at data on 179 patients with relapsed and refractory IDH1-mutant AML who were part of a phase I dose-escalation and dose-expansion trial. Median patient age was 67. Evaluable patients (n=125) included those with relapsed or refractory disease who were treated with a 500-mg daily dose and had 6 months of follow-up. Most patients had primary AML (66%).
With a median follow-up of nearly 15 months, the median OS was 8.8 months in all comers, and 9.3 months for responders that did not achieve CR/CRh.
Overall 25.6% patients had a grade 3 or higher treatment-related adverse event, the most common of which were prolongation of the QT interval (7.0%), IDH differentiation syndrome (4.7%), anemia (2.3%), and thrombocytopenia (1.9%). Diarrhea, decreased platelet counts, hypoxia, febrile neutropenia, and leukocytosis each occurred in 1.2% of patients.
DiNardo highlighted IDH differentiation syndrome as a side effect to be aware of, but this can successfully be treated with steroids when found early, she said.
Ivosidenib and enasidenib are both currently being tested in the frontline setting with ‘7+3’ chemotherapy for IDH1/IDH2-positive AML, and promising results were presented at the 2017 American Society of Hematology annual meeting.
The study was funded by Agios Pharmaceuticals. S several co-authors are company employees.
Pollyea, DiNardo and co-authors disclosed multiple relevantrelationships with industry including Agios, Bayer, Celgene, Pfizer, Novartis, Servier, Pierre Fabre, Amgen, Incyte, Jazz, Daiichi Sankyo, ImmunoGen, MacroGenics, Ono, Seattle Genetics, Sunesis, GlycoMimetics.
Wang disclosed relevant relationships with Abbvie, Amgen, Arog, ImmunoGen, Pfizer, Spectrum, Incyte, Jazz Pharmaceuticals, and Novartis.
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#ASCO18: Evidence Grows for Colon Cancer Occurrence in Younger People


The recent observation of an increasing incidence of colorectal cancer among younger people in the U.S. is also being seen in other developed countries, which has implications for screening recommendations, a researcher reported here.
In the U.S., the annual percent change in colon cancer for individuals age <55 between 1988 and 2007 was +3.08% (95% CI 2.61-3.56), compared with an annual percentage change of -4.20 (95% CI -5.11 to -3.28) for those ages ≥55, according to Rashid Lui, MD, of the Chinese University of Hong Kong.
And for rectal cancer in the U.S., the annual percent change for those <55 was +3.30% (95% CI 2.41-4.20) compared with a change of -3.35% (95% CI -3.82 to -2.87) for those >55, Lui said in a presentation at Digestive Disease Week.
“As we all know, the risk of colorectal cancer increases with age, and the incidence really starts to kick off at around 50 years of age, so most screening programs have recommended starting screening at that time point,” Lui said.
A recent report from the American Cancer Society noted that the incidence of colon cancer increased by 1% to 2.4% annually since the mid 1980s in individuals ages 20 to 39, and by 0.5% to 1.3% since the 1990s among those ages 40 to 54, whereas the incidence in those >55 has been declining since the 1980s.
This led the society to issue a recommendation just this week that screening begin at age 45 for individuals at average risk. This recommendation also was endorsed by the American Gastroenterological Association.
“These observations also raise the question as to whether the increasing trend among younger adults is limited to the U.S., or whether it is an emerging global problem,” Lui said.
Of particular concern is that some studies have suggested that in younger patients, colorectal cancer can present at more advanced stages or even with metastases, he said.
To explore these temporal trends in incidence, Lui’s group extracted data from the International Agency for Research on Cancer, analyzing data from six jurisdictions that have collected complete data since 1988: the U.S., the U.K., Sweden, Japan, China (Shanghai and Hong Kong).
From a total population of 113,643,145 individuals, there were 65,909 incident cases of young-onset colorectal cancer as of 2007.
The “young-shift” in colorectal cancer seen in the U.S. was also observed elsewhere. For instance, the annual percent change for rectal cancer in Sweden was +1.26% (95% CI 0.67-1.85) for patients <55 compared with -0.33% (95% CI -0.63 to -0.02) for those >55, and change in colon cancer rates in Hong Kong were +1.65% (95% CI 0.93-2.38) for younger individuals and -1.29 % (95% CI -2.44 to -0.14) for those who were older.
In other areas, there also has been an increase in rates among the younger population without a decline in incidence among older individuals. This pattern was seen for colon cancer in Sweden and Shanghai, and for rectal cancer in the U.K., Hong Kong, and Shanghai.
“This study suggests that earlier colorectal screening should be considered,” he concluded, adding that his group plans further work investigating trends in colorectal cancer in developing nations.
Limitations of the study included its cross-sectional design and relative short 20-year follow-up.
Obesity and Colon Ca
In a separate presentation, Po-Hong Liu, MD, of Massachusetts General Hospital in Boston, explored the potential role of obesity in the “alarming” trends of colorectal cancer in younger patients.
Using data on height, weight, lifestyle, dietary factors, and medications from the Nurses’ Health Study II and cancer cases from medical record reviews and the National Death Index, Liu’s group identified 121 incident cases of colorectal cancer since 1989 among women age <50, during 1,431,510 person-years of follow-up.
For those whose BMI was ≥30, defined as obese, the multivariate hazard ratio for young-onset colorectal cancer was 1.92 (95% CI 1.08-3.44) compared with those whose BMI was normal. The risk also was consistent among those with a family history of the disease and for those who had not undergone colonoscopy within the previous 10 years.
Further analysis determined that obesity was significantly associated with colon cancer (HR 2.07, 95% CI 1.02-4.20), and nonsignificantly associated with rectal cancer (HR 1.59, 95% CI 0.55-4.60).
Change in weight since adolescence also was associated with an increased risk. Compared with women who had maintained their weight within 5 kg (about 2.2 lbs) since age 18, those who had gained ≥40 kg also had an increase risk of early-onset colorectal cancer (HR 1.96, 95% CI 0.92-4.19).
“Obesity may play a significant role in the pathogenesis of early onset colorectal cancer, through many possible mechanisms such as changes in the microbiota and increases in adipokines,” she said.
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