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Therapeutics Oral Abstract Ses- sion on June 3. That program included 55 patients: eight from an adult phase I study of advanced solid tumors, 12 from a pediatric phase I/II trial of advanced solid tumors, and 35 from the phase II NAVIGATE study—a basket trial of patients age 12 years or older with ad- vanced solid tumors that were TRK fusion–positive. The median age in the study was 45 (range: 0.3-76.0), and the 55 patients had 17 dis- tinct cancer types. The most commonly represented were salivary gland tumors (22%), infantile fibrosarcoma (13%), and thyroid cancer (9%). No- tably, there was no central screening for TRK fusions in these patients; instead, the investigators accepted identi- fication of TRK fusion cancers from any certified laboratory in the field, and 15 unique labs contributed at least one case. Among the 50 patients with neutropenia (46.0% vs. 4.0%). Grade 3/4 neutropenia occurred in 26.5% of the combination treatment arm compared with 1.7% in the placebo arm with few instances of febrile neutro- penia, and grade 3/4 diarrhea in 13.4% compared with 0.4% of patients, respectively. The diarrhea occurred early, typically in the first treatment cycle, Dr. Sledge said, and the intensity and frequency was "strongly related" to the start- ing dose of abemaciclib. In- stances of severe diarrhea were quite rare after dose reduction, he added. Adverse events led to dose reduction in 42.9% of patients in the abemaciclib arm com- pared with 1.3% in the placebo arm, and discontinuation of the study drug in 15.9% com- pared with 3.1%, respectively. There were no significant dif- ferences in deaths between the two arms. Discussant Ingrid A. Mayer, MEETING COVERAGE LION Trial Results 3A History of Immunotherapy in Solid Tumors 8A ICON6 Results 8A Strategic Combinations in Ovarian Cancer 18A Aldoxorubicin Prolongs PFS in Some Sarcomas Compared With Standard Treatments 20A Treatment Options for Localized, Metastatic Melanoma 20A No RFS Increase With Combined Regimen for Stage III/IVA Endometrial Cancer 21A In Briefs 21A MONALEESA-2 Secondary Analyses 22A Dr. Siddhartha Mukherjee on the 'Growing Up' of Cancer Therapy 23A Future of Oncology Informatics 1B CT Screening and Tobacco- Cessation Programs 20B The Precision Medicine Landscape 1C Plenary Preview 1D PHYSICIAN-AUTHORED Expert Editorials Biosimilars in the Changing Cancer Care Landscape 10A Checkpoint Inhibitors in Melanoma: Lessons for Other Cancers 12A Implementing Precision Oncology 1B The Changing Face of Prostate Cancer 14B Improving Quality and Value of Cancer Care for Older Patients 26B Ipilimumab in Melanoma 1C RET Rearrangements in NSCLC 24C Tumor Neoantigens in Personalized Cancer Immunotherapy 32C Clinical Corner TKIs and Pregnancy in CML 6B ASCO NEWS 2011 Plenary: The 'Beginning of the Renaissance' for Melanoma 3B ASCO-SITC Clinical Immuno-Oncology Symposium Highlights 21B 2017 GI Cancers Symposium Highlights 9C Guideline: Cardiac Dysfunction in Cancer Survivors 10C SPECIAL AWARDS Science of Oncology Award: Dr. Brian J. Druker 1B 2017 ASCO-ACS Award: Dr. Dean E. Brenner 1C HIGHLIGHTS See TRK Fusions, Page 3A See Abemaciclib, Page 3A DAILY NEWS SUNDAY · J U N E 4, 20 1 7 A Larotrectinib Highly Active in Cancers With TRK Fusions T he novel TRK inhibi- tor larotrectinib showed consistent and durable antitumor activity in ad- vanced cancers with TRK fu- sions, according to results from early trials (Abstract 2501). TRK is uncommonly ex- pressed in normal tissues and in most cancers. TRK fusions are found in a diverse range of cancer types. In common cancers, they tend to be very rare, occurring in between 0.2% and 3.0% of cases. But in some rare cancers the fusions appear to be a defining char- acteristic and are present in nearly every case. Larotrectinib is the first and only selective pan-TRK inhibi- tor currently under develop- ment, David M. Hyman, MD, of Memorial Sloan Kettering Cancer Center, said as he pre- sented results of the drug's early development program during the Developmental Therapeutics—Clinical Phar- macology and Experimental Significant Increase in PFS With Abemaciclib Plus Fulvestrant in Metastatic Breast Cancer T he CDK4/6 inhibitor abe- maciclib combined with the estrogen inhibitor ful- vestrant may significantly reduce the risk of disease pro- gression and increase the ob- jective response rate in women with metastatic breast cancer, according to the results of the MONARCH 2 study presented during the Breast Cancer— Metastatic Oral Abstract Session on June 3 (Abstract 1000). The combination protocol reduced the risk of disease pro- gression by 45% with a toler- able side effect profile, lead author and presenter George W. Sledge Jr., MD, FASCO, of Stanford University, said. The results were simultaneously published in the Journal of Clini- cal Oncology. The MONARCH 2 study was a double-blind, phase III trial involving 669 women with hor- mone receptor–positive, HER2- negative advanced breast cancer resistant to endocrine therapy. Participants were randomly assigned 2:1 to either a com- bination of abemaciclib and fulvestrant or to placebo and fulvestrant. The initial dose of 200 mg twice daily of abemaci- clib was reduced to 150 mg twice daily because of diarrhea after 178 patients enrolled, Dr. Sledge said. The fulvestrant dose was 500 mg twice daily. The dose reduction did not change study results, he added. At the median follow-up of 19.5 months, the median progression-free survival (PFS) in the combination treatment arm was 16.4 months com- pared with 9.3 months in the placebo arm (hazard ratio [HR] 0.553, 95% CI [0.449, 0.681]; p < 0.0000001) in all patient sub- groups. Patients with measurable disease receiving combination treatment achieved a twofold higher objective response rate compared with those receiving fulvestrant alone (48.1%, 95% CI [42.6%, 53.6%] for abemaci- clib vs. 21.3%, 95% CI [15.1%, 27.6%] for placebo). "This response rate is, to the best of our knowledge, the highest recorded in an endocrine-resistant popula- tion," Dr. Sledge said. The median duration of re- sponse has not yet been reached in the combination group, he added. It was 25.6 months in the placebo cohort. The most common treatment- related adverse events in the combination arm compared with the placebo arm were di- arrhea (86.4% vs. 24.7%) and Pembrolizumab Promising in Subset of Sarcomas P embrolizumab is a poten- tially viable treatment for a subset of sarcomas, with promising activity in un- differentiated pleomorphic sar- coma (UPS) and liposarcoma in a phase II clinical trial. Melissa A. Burgess, MD, of the Univer- sity of Pittsburg, presented final results and biomarker analyses from the SARC028 multicenter trial (Abstract 11008) at the Sar- coma Oral Abstract Session on June 2. Response in UPS correlated with PD-L1 status, and baseline infiltrating cytotoxic T cells also correlated with response, Dr. Burgess said. SARC028 is a multicenter tri- al evaluating single-agent pem- brolizumab in patients with advanced soft tissue sarcomas (STS) and bone sarcomas. The primary endpoint was objec- tive response rate (ORR) by RECIST 1.1, and secondary objectives included safety and tolerability, progression-free survival (PFS), overall survival (OS), immune-related response rate, and analysis of pretreat- ment PD-L1 tumor expression and response. The STS arm included 10 patients in four cohorts: UPS, dedifferentiated liposarcoma, synovial sarcoma, and leio- myosarcoma. The bone sar- coma arm had 40 patients, in- cluding 22 with osteosarcoma, 13 with Ewing sarcoma, and five with chondrosarcoma. Most patients in each arm re- ceived two or more previous treatments. Patients received 200 mg of pembrolizumab intravenously every 3 weeks. Biopsies were taken before treatment and while patients were receiving treatment. Tumors were as- sessed for PD-L1 expression and immune infiltrates using mul- ticolor immunohistochemistry (IHC). In the overall study, with a median follow-up of 19 months, the projected overall See Pembrolizumab, Page 8A Dr. George W. Sledge Jr. presents Abstract 1000.

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