2018 ASCO Annual Meeting!
Session: Tumor Genomics: Finding the Target, Hitting the Target
Type: Clinical Science Symposium
Time: Saturday June 2, 8:00 AM to 9:30 AM
Location: Hall D1
Results from molecular analysis for therapy choice (MATCH) arm I: Taselisib for PIK3CA-mutated tumors.
Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 101)
Author(s): Ian E. Krop, Opeyemi Jegede, Juneko E. Grilley-Olson, Josh David Lauring, Stanley R. Hamilton, James A. Zwiebel, Shuli Li, Lawrence Rubinstein, Austin Doyle, David R. Patton, Edith P. Mitchell, Carlos L. Arteaga, Barbara A. Conley, David Sims, Lyndsay Harris, Alice P. Chen, Keith Flaherty; Dana-Farber Cancer Institute, Boston, MA; University of North Carolina at Chapel Hill, Chapel Hill, NC; Johns Hopkins, Baltimore, MD; The University of Texas MD Anderson Cancer Center, Houston, TX; Cancer Therapy Evaluation Program, Bethesda, MD; National Cancer Institute, Bethesda, MD; National Cancer Institute, Rockville, MD; National Cancer Institute, Bethesda, MD, US; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA; Vanderbilt University Ingram Cancer Center, Nashville, TN; Frederick National Laboratory of Cancer Research, Frederick, MD; Cancer Diagnosis Program, National Cancer Institute, Rockville, MD; Early Clinical Trials Development Program, DCTD, National Cancer Institute at the National Institutes of Health, Bethesda, MD; Massachusetts General Hospital, Boston, MA
Background: MATCH is a trial that assigns patients (pts) with solid tumors, lymphomas, or multiple myeloma to specific targeted therapies based on genetic alterations identified in fresh tumor biopsies. Arm I evaluated the PI3-kinase inhibitor taselisib in pts with activating mutations in PIK3CA, the catalytic subunit of PI3-kinase. Methods: Pts with KRAS mutations or PTEN mutation or loss were excluded, as were pts with breast or squamous lung cancer. Pts received taselisib 4 mg po daily on 28 d cycles until progression or intolerable toxicity. Staging was every 2 cycles. The primary endpoint was objective response (OR); secondary endpoints were PFS, 6-month PFS, and predictive biomarkers. Results: 65 pts (enrolled 3/2016-4/2017) received ≥1 dose of study therapy; 45 tumor types were represented; 38% of pts had > 3 prior lines of therapy. There were no ORs, but prolonged stable disease was observed (estimated PFS6 rate 27%, 90% CI 19%-39%), and 2 pts remain on study > 1 yr. The most common toxicities were fatigue (38%), diarrhea (38%) and nausea (34%), all predominately grade 1-2, with 2% of pts requiring dose reductions, and 11% discontinuing taselisib because of toxicity. No hyperglycemia or rash were observed. PIK3CA mutations occurred in the helical domain (HD, 69%), kinase domain (KD, 17%), or other domains (14%). There was an observed trend (non-significant) toward longer PFS in tumors with KD mutations compared to HD or other mutations (median PFS 4.6 mo vs 3.5 mo vs 1.8 mo, respectively). Co-occurring mutations were detected in 67% of tumors. In exploratory analyses, TP53/MDM2 alterations (n = 24) were associated with PFS < 6 mo, and enrichment for PFS ≥ 6 mo was observed in pancreatic-biliary tumors/cholangiocarcinoma (3/6) and adenoid cystic carcinoma (3/4). Only 1 of 9 pts with BRAF, NRAS, HRAS, MAP2K1, MAPK1, or NF1 mutations achieved PFS ≥ 6 mo. Conclusions: In a mixed histology cohort selected for activating PIK3CA mutations, taselisib did not achieve any ORs, although 27% of pts had PFS ≥ 6 mo. PIK3CA mutation independent of histology is an insufficient predictor of taselisib activity. Associations of individual histologies and PIK3CA mutation subtypes with PFS may be worthy of further study. Clinical trial information: NCT02465060