Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (33602685)
Authors Sharma P, Abramson VG, O'Dea A, Nye L, Mayer I, Pathak HB, Hoffmann M, Stecklein SR, Elia M, Lewis S, Scott J, De Jong JA, Wang YY, Yoder R, Schwensen K, Finke K, Heldstab J, LaFaver S, Williamson SK, Phadnis MA, Reed GA, Kimler BF, Khan QJ, Godwin AK
Title Clinical and Biomarker Results from Phase I/II Study of PI3K Inhibitor Alpelisib plus Nab-paclitaxel in HER2-Negative Metastatic Breast Cancer.
URL
Abstract Text PIK3CA mutations are common in breast cancer and promote tumor progression and treatment resistance. We conducted a phase I/II trial of alpelisib (α-specific PI3K inhibitor) plus nab-paclitaxel in patients with HER2-negative metastatic breast cancer (MBC).Eligible patients had HER2-negative MBC with any number of prior chemotherapies. Phase I was 3+3 dose-escalation design with three dose levels of alpelisib (250, 300, and 350 mg) daily plus nab-paclitaxel 100 mg/m2 administered on days 1, 8, and 15 every 28 days. Phase II was according to Simon's two-stage design. PIK3CA mutations in tumor/circulating tumor DNA (ctDNA) were assessed. Primary endpoints were recommended phase II dose (RP2D) and objective response rate (ORR). Additional endpoints included safety, pharmacokinetics, progression-free survival (PFS), and association of PIK3CA mutation with outcomes.A total of 43 patients were enrolled (phase I, n = 13 and phase II, n = 30). A total of 84% had visceral disease and 84% had prior taxane. No dose-limiting toxicities occurred in phase I. RP2D was alpelisib 350 mg daily plus nab-paclitaxel 100 mg/m2 on days 1, 8, and 15. Hyperglycemia (grade 3, 26% and grade 4, 0%), neutropenia (grade 3, 23% and grade 4, 7%), diarrhea (grade 3, 5% and grade 4, 0%), and rash (grade 3, 7% and grade 4, 0%) were the most common adverse events. Among 42 evaluable patients, ORR was 59% (complete response, 7% and partial response, 52%), 21% of whom had response lasting >12 months; median PFS was 8.7 months. A total of 40% of patients demonstrated tumor and/or ctDNA PIK3CA mutation; patients with tumor/ctDNA mutation demonstrated better PFS compared with those without mutation (11.9 vs. 7.5 months; HR, 0.44; P = 0.027). Patients with normal metabolic status had longer PFS compared with prediabetic/diabetic patients (12 vs. 7.5 months; P = 0.014). No pharmacokinetics interactions were detected.The alpelisib plus nab-paclitaxel combination was well tolerated and shows encouraging efficacy, especially in patients with PIK3CA-mutated tumor/ctDNA. The impact of metabolic status on response to this combination merits further investigation.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PIK3CA act mut Her2-receptor negative breast cancer predicted - sensitive Alpelisib + Nab-paclitaxel Clinical Study - Cohort Actionable In a Phase I/II trial, Piqray (Alpelisib) and Abraxane (nab-paclitaxel) combination treatment resulted in improved clinical benefit rate (100% vs 68%; OR=1.47, P=0.013) and median progression-free survival (11.9 vs 7.5 mo.; HR=0.44, P=0.027) and longer median overall survival (26.7 vs. 14.9 mo.; HR=0.59, P=0.19) in patients with ERBB2 (HER2)-negative metastatic breast cancer harboring activating PIK3CA mutations compared to patients without PIK3CA mutations (PMID: 33602685; NCT02379247). 33602685