AMG 420, a bispecific T-cell engager (BiTE) from Amgen for the treatment of patients with relapsed and refractory multiple myeloma (RRMM), has found positive preliminary results in a phase 1 trial. The development of AMG 420 adds another contender to the immunotherapy category for treating MM.
In 2016, Amgen bought the BiTE platform from Boehringer Ingelheim.1BiTE combats cancer by directing T cells to destroy cancer cells. It consists of 2 single chain antibodies: one specific for B-cell maturation antigen (BCMA), a tumor antigen, and the other specific for CD3, a protein on the surface of T cells. By binding to BCMA and CD3, BiTE technology forms a bridge between the T cell and the tumor cell. This lets the T cell target the tumor cell, resulting in tumor cell lysis and reduced tumor burden and therefore halting the progression of the cancer.1-3
By 2018, AMG 420, an anti-BCMA BiTE product, was considered potentially beneficial in patients with RRMM. Preliminary results were reviewed, and findings showed that 5 patients on AMG 420 were able to obtain stringent complete responses, with 4 of the patients having negative minimal residual disease exceeding 10 months.2AMG 420 is still in phase 1 trials, but the positive results may streamline AMG 420 ahead into future clinical trials.
Another drug that has entered the MM drug development market is bb2121, an anti-BCMA chimeric antigen receptor (CAR) T drug developed by Celgene with bluebird bio, Inc, also designed to treat patients with RRMM. Although it was created to target the same population as AMG 420, bb2121 is a gene therapy. T cells extracted from the white blood cells of a patient are collected and genetically modified to recognize BCMA. They are then returned to the body of the patient, so they can target MM tumor cells that express the BCMA.4
Results from phase 1 study of bb2121 were revealed at the annual meeting of the American Society of Clinical Oncology in June. The overall response rate in the 18 patients with RRMM was 94%, with 56% (10 patients) having complete response. Nine of the 10 patients were also MRD-negative. At 40 weeks, the median duration of response and progression-free survival were not reached.5Currently, bb2121 is in phase 2 and 3 trials, for which Celgene and bluebird bio, Inc, had begun testing the efficacy and safety of bb2121 and comparing it with other treatment options for MM (NCT03361748, NCT0365112).
Right now, there is reason to believe that AMG 420 may have similar efficacy to bb2121 for treating patients with RRMM. But this assumption will not be verified until the results of longer-term data are available. The development of these new drugs in the field of MM is groundbreaking, and it will be very interesting to see where these drugs will fit within MM treatment guidelines.
1. AMG 420. Immuno-Oncology News website. immuno-oncologynews.com/amg-420. Accessed September 19, 2018.
2. Chrisomalis T. Amgen looks to enter multiple myeloma space: can it compete? Seeking Alpha website. seekingalpha.com/article/4205437-amgen-looks-enter-multiple-myeloma-space-can-compete. Updated September 10, 2018. Accessed September 19, 2018.
3. Amgen Oncology. BiTE: engage the immune system. biteantibodies.com. Accessed September 19, 2018.
4. Bb2121. Immuno-Oncology News website. immuno-oncologynews.com/bb2121. Accessed September 19, 2018.
5. Raje NS, Berdeja JG, Lin Y, et al. bb2121 anti-BCMA CAR T-cell therapy in patients with relapsed/refractory multiple myeloma: updated results from a multicenter phase 1 study. Presented at: the 2018 Annual Meeting of the American Society of Clinical Oncology; June 1, 2018; Chicago, IL. Abstract 8007. abstracts.asco.org/214/ AbstView_214_211179.html.
Celyad, a biopharmaceutical company that focuses on the development of chimeric antigen receptor (CAR) T-cell therapies, recently announced1that the FDA accepted its investigational new drug (IND) application for CYAD-101, the first non—gene-edited allogeneic clinical program.
Traditionally, CAR T-cell therapies are created by genetically modifying a patient’s immune cells to target specific cancer cells before injecting them back into the patient. However, this can be difficult because researchers aren’t always able to collect enough cells from a patient to create the treatment. Conversely, in an allogeneic CAR T-cell therapy, immune cells are collected from healthy donors, rather than the patient.
The Allo-SHRINK trial looks to evaluate the safety and clinical activity of CYAD-101 in patients with unresectable colorectal cancer in combination with standard chemotherapy. “We are pleased to have achieved this im- portant milestone. Celyad is the first company clinically evaluating a non— gene-edited CAR T candidate, which, we believe, offers significant advantages over gene-edited approaches,” Christian Homsy, MD, CEO of Celyad, said in a statement.
CYAD-101 is based on features of the company’s investigational autologous CYAD-01 CAR T with a novel peptide, TCR Inhibiting Molecule (TIM). This prevents the patients’ immune system from recognizing the cells as foreign. The cells in CYAD-01 produce a chimeric receptor, called natural killer group 2D (NKG2D), that recognizes multiple tumor proteins.
Celyad’s investigational autologous CYAD-01 treatment is currently being tested in 3 phase 1 trials for different cancers, including SHRINK,2which is investigating increasing doses of CYAD-01 with chemotherapy in patients with colorectal cancer whose liver metastasis can be removed by surgery; LINK,3which is examining increasing doses of CYAD-01 in patients with colorectal cancer with liver metastases that cannot be removed by surgery; and THINK,4which is evaluating CYAD-01 in 7 types of refractory cancers, including 5 solid tumors.
“Our non—gene-edited program consists of a family of technologies aimed at reducing or eliminating T-cell receptor (TCR) signaling without requiring genetic manipulation. CYAD-101 is part of a robust clinical development plan, establishing the foundations of next-generation CAR T products,” said Homsy.
1. Celyad announces FDA acceptance of IND application for CYAD-101, a first-in-class non-gene edited allo- geneic CAR T candidate [press release]. Mont-Saint-Guibert, Belgium: Celyad; July 24, 2018. globenewswire.com/news-release/2018/07/24/1540949/0/en/Celyad-Announces-FDA-Acceptance-of-IND-Application-for-CYAD-101-a-First-in-Class-Non-Gene-Edited-Allogeneic-CAR-T-Candidate.html. Accessed August 4, 2018.
2. Dose Escalation and Dose Expansion Phase 1 Study to Assess the Safety and Clinical Activity of Multiple Doses of NKR-2 Administered Concurrently With FOLFOX in Colorectal Cancer With Potentially Resectable Liver Metastases (SHRINK). clinicaltrials.gov/ct2/show/NCT03310008. Updated June 1, 2018. Accessed August 4, 2018.
3. Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer (LINK). clinicaltrials.gov/ct2/show/NCT03370198. Updated June 1, 2018. Accessed August 4, 2018.
4. A Dose Escalation Phase 1 Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications (THINK). clinicaltrials.gov/ct2/show/NCT03018405. Updated January 18, 2018. Accessed August 4, 2018.
With Healthy People 2020 goals of achieving health equity, eliminating disparities, and improving the health of all groups, cancer screening plays an integral role in achieving these goals. However, cancer screening rates in the United States fall short of these targets and significant disparities exist among subgroups, according to CDC data.1
The agency’s research focused on breast, cervical, colorectal, and prostate cancers, as these accounted for nearly 40% of new cancer diagnoses and close to 20% of cancer deaths in 2013. Among the goals of Healthy People 2020 are increasing the proportion of women aged 21 to 65 years screened for cervical cancer, women aged 50 to 74 years screened for breast cancer, and men and women aged 50 to 75 years screened for colorectal cancer. Their goals also include reducing prostate cancer deaths.
Using the National Health Interview Study, researchers collected data from participants on Papanicolaou (Pap) tests, hysterectomies, mammograms, pros- tate-specific antigen (PSA) tests, and endoscopic exams and fecal occult blood tests (FOBTs) screening for colorectal cancer. Women were considered to have been screened recently for breast cancer if they had a mammogram within 2 years and screened for cervical cancer if they had a Pap test within 3 years.
Having an FOBT within the past year, a flexible sigmoidoscopy within 5 years and an FOBT within 3 years, or a colonoscopy within 10 years signified a recent colorectal cancer screening. The authors noted that at the time of analysis, the US Preventive Services Task Force (USPSTF) was following its 2012 guideline that recommended against routine PSA screening.
Of the 83% of women who received a recent Pap test, women aged 21 to 30 and women aged 51 to 60 years were less likely to have been screened. More than two-thirds (71.7%) also reported having a recent mammogram. Similar to Pap testing, mammography testing was least likely among those aged 50 to 64 years. Although screening rates were high, they fell short of the Healthy People 2020 targets of 93% for Pap tests and 81% for mammography. For colorectal screening, 63.4% of women and 61.9% of men reported having a recent screening, falling below the target of 80%. Across the 3 screening methods, having less than a high school education, having no usual source of care, having public insurance, and being underinsured were associated with lower testing rates.
Among men, 35.8% reported having a recent PSA test in the past year.
Between 2000 and 2015, Pap test use declined by 4.3% among women with a usual source of care and mammography rates declined by 3%. Only use of colorectal cancer screening has increased significantly and consistently, rising 25.1% among women between 2000 and 2010. Rates stayed stable between 2010 and 2013 and then increased slightly in 2015. Colorectal cancer screening among men also increased significantly.
Use of a PSA test declined by 9.2% from 2008 to 2013 but remained stable between 2013 and 2015. The authors noted that this drop can be attributed to USPSTF’s recommendation against routine screening and, subsequently, a drop in the test being offered by physicians and used by patients. Earlier this year, USPSTF updated their recommendation,2 calling for men aged 55 to 69 years to make their own decision on whether to be screened periodically for prostate cancer after they have had a conversation with their physician on potential benefits and harms.
“One approach to improving screening use across all subgroups would be for physicians to recommend screening to all age-appropriate patients, including traditionally underserved groups,” they wrote. They add that physician enthusiasm and outreach with tailored or innovative strategies to educate and inform may increase knowledge and intention to screen among these underserved groups.
1. CDC. Patterns and trends in cancer screening in the United States. CDC website. cdc.gov/pcd/issues/2018/17_0465.htm. Published July 26, 2018. Accessed July 31, 2018.
2. Rosenberg J. USPSTF recommends patient choice for prostate cancer screening.The American Journal of Managed Care®website. ajmc.com/newsroom/uspstf-recommends-patient-choice-for-prostate-cancer-screening. Published May 10, 2018. Accessed July 31, 2018.
A recent study1found that the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib extended progression-free survival (PFS) and improved
quality of life over chemotherapies for patients with metastatic human epidermal growth factor 2—negative breast cancer and mutations in theBRCA 1/2genes.
The results of the EMBRACA trial, an international randomized phase 3 study led by researchers at The University of Texas MD Anderson Cancer Center, were recently published inthe New England Journal of Medicine. Researchers enrolled 431 patients with locally advanced or metastatic and hereditary BRCA 1/2 gene mutations in the study. Participants were randomized 2:1 to receive either talazoparib (n = 287) or a physician’s choice of single-agent therapy (n = 144), which was either capecitabine, eribulin, gemcitabine, or vinorelbine. Of the patients enrolled in the trial, 54% had hormone receptor—positive disease and 46% had triple-negative breast cancer;BRCA 1andBRCA 2mutations were split at 45% and 55%, respectively.
“The trial found that talazoparib provides a significant clinical benefit to all patient subgroups, including those with hormone receptor—positive and triple-negative disease,” Jennifer Litton, MD, associate professor of breast medical oncology and the corresponding author of the study, said in a statement.2“The results of this trial are quite exciting and indicate talazoparib is a novel treatment option for patients with metastatic breast cancer andBRCA mutations.”
Notably, the primary endpoint of PFS was met in the talazoparib arm, as the median PFS was 8.6 months in the talazoparib cohort and 5.6 months in physician’s choice. Researchers evaluated time to deterioration of overall health as the secondary endpoint of the study. Patient-reported quali- ty-of-life measures found a greater time to deterioration of overall health in the talazoparib arm compared with the physician’s choice arm: 24.3 versus 6.3 months.
“It is encouraging to see this oral PARP inhibitor was well tolerated and superior to chemotherapy alone,” said Litton. To follow up the positive results of this trial, researchers have already begun a phase 1 study evaluating talazoparib combination treatment.
1. Litton J, Rugo H, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation.N Engl J Med. 2018;379(8):753-763. doi: 10.1056/NEJMoa1802905.
2. PARP inhibitor improves progression-free survival in patients with advanced breast cancers and BRCA mutations [press release]. Houston, Texas: MD Anderson Cancer Center; August 15, 2018. mdanderson.org/ newsroom/2018/08/parp-inhibitor-improves-progression-free-survival-in-patients-with-advanced-breast-cancers-and-BRCA-mutations.html. Accessed August 16, 2018.
What type of cervical cancer screening should a woman get, if any, and how often? The latest recommendation1from the United States Preventive Services Task Force (USPSTF) said in August that it depends on a woman’s age and other factors, but those 30 or older have a new option.
The number of deaths2from cervical cancer in the United States has decreased since widespread cervical cancer screening began, falling to 2.3 from 2.8 deaths per 100,000 women. Still, 4170 will die from the disease this year, according to the American Cancer Society. Most will not have been adequately screened.
To update its 2012 recommendation, the USPSTF reviewed evidence on screening for cervical cancer, looking at clinical trials and cohort studies that evaluated screening with high-risk human papillomavirus (hrHPV) testing3alone or together with hrHPV using a cytology-based Papanicolaou (Pap) smear, where cells are scraped from the back of the cervix. The 2 tests together are called cotesting.
For women aged 30 to 65, there are 2 options: screening by either a Pap test every 3 years or a Pap and hrHPV test every 5 years. The recommendation is a slight change from draft guidelines, which recommended that women get just 1 test, instead of a co-test. Overall, the USPSTF gave an “A” recommendation to screening women aged 21 to 65 years, but did not recommend testing for those younger than 21 or older than 65. For women aged 21 to 30, screening should be done by a Pap test every 3 years.
Under current law, preventive services receiving an A or B grade must be covered by most private insurance plans, with no co-pay for patients. Other screening tests and services with different grades are up to the payer.
As over 99% of all cervical cancers are associated with HPV, testing for the infection has been touted as an alternate option for cervical cancer screening. Previous research has indicated that HPV testing alone or combined with a Pap smear is linked to increased detection of precancerous lesions in the first screening round, followed by a subsequent reduction in precancerous lesions.
In a joint statement, 3 of the nations’ top women’s healthcare groups called the recommendation “largely in line” with clinical guidance with their own.
“With a number of screening options now available, the new guidelines emphasize the importance of the patient—provider shared decision-making process to assist women in making an informed choice about which screening method is most suitable for them,” said the statement4 from the American College of Obstetricians and Gynecologists (ACOG), the Society of Gynecologic Oncology, and the ASCCP. “However, more importantly, there needs to be a continued effort to ensure all women are adequately screened, because a significant number of women in the country are not. It’s also essential for women to have access to all of the tests and that they are appropriately covered by insurance companies.”
Discussion about insurance coverage5 of the tests based on USPSTF recommendations was a source of lively discussion at a session of the annual meeting of ACOG earlier this year.
Screening women who have had a hysterectomy with removal of the cervix for indications other than a high-grade precancerous lesion or cervical cancer does not offer any benefit, the USPSFT said.
1. US Preventive Services Task Force. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;320(7):674-686. doi: 10.1001/jama.2018.10897.
2. Rosenberg J. Cancer screening rates in the US fall short of healthy people 2020 targets.AJMC®website. ajmc. com/focus-of-the-week/cancer-screening-rates-in-the-us-fall-short-of-healthy-people-2020-targets. Published July 31, 2018. Accessed August 21, 2018.
3. Rosenberg J. Study suggests HPV test more accurate than pap smear for cervical cancer screening.The American Journal of Managed Care®website. ajmc.com/newsroom/study-suggests-hpv-test-more-accurate-than-pap-smear-for-cervical-cancer-screening. Published July 5, 2018. Accessed August 21, 2018.
4. Leading women’s health care groups issue joint statement on USPSTF final cervical cancer screening recommendations. American College of Obstetricians and Gynecologists website. acog.org/About-ACOG/News- Room/Statements/2018/USPSTF-Final-Cervical-Cancer-Screening-Recommendations. Published August 21, 2018. Accessed August 21, 2018.
5. Caffrey M. USPSTF session brings lively comments on link between ratings, coverage.The American Journal of Managed Care®website. ajmc.com/conferences/acog-2018/uspstf-session-brings-lively-comments-on-link- between-ratings-coverage. Published April 30, 2018. Accessed August 21, 2018.
The FDA has approved ivosidenib, the first targeted therapy for the treat- ment of relapsed or refractory acute myeloid leukemia (AML) in patients with specific mutations in the isocitrate dehydrogenase-1 (IDH1) gene. Ivosidenib, a tablet to be sold as Tibsovo by Agios Pharmaceuticals, was approved July 20, 2018, for use with an FDA-approved companion diagnostic.
“Tibsovo is a targeted therapy that fills an unmet need for patients with relapsed or refractory AML who have an IDH1 mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.1“The use of Tibsovo is associated with a complete remission in some patients and a reduction in the need for both red cell and platelet transfusions.”
Ivosidenib is an IDH1 inhibitor, which means it works to decrease abnormal production of oncometabolite 2-hydroxyglutarate (2-HG), which causes the differentiation of malignant cells. Patients who are found to have the IDH1 mutation in their blood or marrow sample would be considered for the therapy. The FDA also approved the RealTime IDH1 Assay to detect the genetic mutation.
Approval of ivosidenib was based on results from a single-arm trial of 174 patients, and those results showed that 32.8% of the patients had a compete response or a partial hematologic recovery that lasted a median of 8.2 months. Of the 110 patients who required blood or platelet transfusion due to AML when the study began, 37% went at least 56 days without needing a transfusion after taking the study drug.
Results were also presented at the June meeting of the American Society of Clinical Oncology and published in theNew England Journal of Medicine,2which noted the drug had few adverse effects (AEs) of grade 3 or higher. Common AEs were fatigue, an increase in white blood cells, joint pain, diarrhea, shortness of breath, swelling in the arms or legs, nausea, and pain or sores in the mouth or throat.
AML forms in the bone marrow and progresses quickly to increase the number of abnormal white blood cells in the bone marrow and bloodstream. According to the National Cancer Institute, 19,520 patients will receive an AML diagnosis this year and 10,670 will die of it in 2018.
1. FDA approves first targeted treatment for patients with relapsed or refractory acute myeloid leukemia who have a certain genetic mutation [press release]. Silver Spring, MD: FDA Newsroom; July 20, 2018. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm614115.htm. August 27, 2018.
2. DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosenib in IDH1-mutated relapsed or refractory AML [published online June 2, 2018]. N Engl J Med. doi:10.1056/NEJMoa1716984.
Chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel, sold as Yescarta, was authorized1 in August 2018 by the European Commission (EC) as a treatment for adult patients with relapsed or refractory diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma after 2 or more lines of systemic therapy. This approval allows Yescarta to be available for use in the 28 countries of the European Union, as well as Norway, Iceland, and Liechtenstein.
The marketing authorization application was approved based on data from the ZUMA-1 trial that investigated axicabtagene ciloleucel in adult patents with refractory aggressive non-Hodgkin lymphoma. In the single-arm trial that enrolled 101 participants, 72% of patients (n = 73) who received a single infusion of axicabtagene ciloleucel responded to therapy, with 51% (n = 52) achieving a complete response.
There are currently 2 CAR T-cell therapies available on the market, and although both treatments have many benefits, they come at a steep price. Yescarta carries a US price tag of $373,000,2and tisagenlecleucel (Kymriah), which treats pediatric and adult B-cell acute lymphoblastic leukemia, comes at the hefty price of $475,000 for a 1-time dose.3
Just 1 day after the EC approved the treatments, the National Institute for Health and Care Excellence (NICE) deemed Yescarta too expensive to justify placing it on Britain’s state-funded health service.4 Although Yescarta was “an exciting innovation in very difficult to treat cancers, with a promise of a cure for some patients,” the price was too high for it to be considered cost-effective, said Meindert Boysen, PharmD, MSc, director, Centre for Health Technology Evaluation at NICE. The United Kingdom list prices of the drugs have yet to be disclosed.
The developer of Yescarta, Gilead, said in a statement that it was in “ongoing discussions with NICE to identify appropriate treatment comparators which can clarify how cell therapy may be made available to patients in the [United Kingdom].” NICE’s evaluation of the cost-effectiveness of Kymriah is still ongoing.
Kymriah was the first CAR T-cell therapy approved in August 2017,5and Yescarta followed shortly thereafter in October 2017.6
1. Yescarta receives European marketing authorization for the treatment of relapsed or refractory DLBCL and PMBCL, after two or more lines of systemic therapy [press release]. Santa Monica, CA: Kite Pharma; August 27, 2018. investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=2364850. Accessed August 28, 2018.
2. Kite’s Yescarta (axicabtagene ciloleucel) becomes first CAR T therapy approved by the FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy [press release]. Foster City and Santa Monica, CA: Business Wire; October 18, 2017. gilead.com/news/press-re- leases/2017/10/ kites-yescarta-axicabtagene-ciloleucel-becomes-first-car-t-therapy-approved-by-the-fda-for- the-treatment-of-adult-patients-with-relapsed-or-refractory-large-bcell-lymphoma-after-two-or-more-lines-of- systemic-therapy. Accessed August 28, 2018.
3. Sagonowsky E. At $475,000 per treatment, is Novartis’ Kymriah a bargain, or just another example of skyrock- eting prices? Fierce Pharma website. fiercepharma.com/pharma/at-475-000-per-treatment-novartis-kymri- ah-a-bargain-or-just-another-example-skyrocketing. Published August 31, 2017. Accessed August 28, 2018.
4. Hirschler B. UK rejects Gilead’s CAR-T cancer cell therapy as too expensive [news release]. London, UK: Reuters; . uk.reuters.com/article/uk-gilead-sciences-britain/uk-rejects-gileads-car-t-cancer-cell-therapy-as-too-expensive-idUKKCN1LD174?feedType=RSS&feedName=domesticNews. Accessed August 28, 2018.
5. FDA approval brings first gene therapy to the United States [press release]. Silver Spring, MD: FDA Newsroom; August 30, 2017. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm. Accessed August 28, 2018.
6. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma [press release]. Silver Spring, MD: FDA Newsroom; October 18, 2017. www.fda.gov/NewsEvents/Newsroom/PressAnnounce- ments/ucm581216.htm. Accessed August 28, 2018.
A recent study evaluated abemaciclib (Verzenio) in a preclinical model of Ewing sarcoma (ES), a rare and highly malignant cancer that occurs in the bone and surrounding tissue of children and adolescents.
Currently, abemaciclib is approved as a monotherapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy. It also holds indications to treat metastatic or advanced HR-positive, HER2- negative breast cancer in combination with an aromatase inhibitor; or plus fulvestrant. Now, researchers are looking to evaluate its effectiveness in ES.
Traditionally, ES treatment includes surgery, radiation, and high dose chemotherapy, which has improved outcomes for patients with localized disease and who have achieved a 5-year overall survival of 50% to 70%. However, in the recurrent or metastatic setting, the 5-year survival rate drops to below 30%.
Researchers characterized in vitro responses of ES cell lines to abemaciclib using various assays and high content imaging. After this was complete, abemaciclib was investigated in vivo in cell line—derived and patient-derived xenograft mouse models of ES as either a monotherapy or in combination with chemotherapy.
The study found that cancer cell lines most sensitive to abemaciclib were previously shown to have D-type cyclin activating features (DCAF). In a large cell line panel consisting of both adult and pediatric tumor cells, 50.0% of ES cell lines and 40.7% of other tumor cell lines with DCAF were highly sensitive to abemaciclib.
Additionally, abemaciclib inhibited tumor growth either alone or in combination with chemotherapy in multiple ES xenograft models. The researchers noted that abemaciclib exhibits a unique mechanism of action that spans cell cycle blockade, DNA demethylation, and activation of the adaptive immune response in an ES model.
“While our data strongly support evaluation of abemaciclib in immune-competent ES models, development of such models has proved elusive,” the study authors wrote.
After the conclusion of this study, researchers recommended that future studies of abemaciclib should include additional preclinical models of adult and pediatric malignancies.
Dowless M, Lowery C, Shackleford T, et al. Abemaciclib is active in preclinical models of Ewing’s sarcoma via multi-pronged regulation of cell cycle, DNA methylation, and interferon pathway signaling [published online August 21, 2018]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-18-1256.