In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 5569-5569
Abstract:
5569 Background: Aberrant PI3K/AKT/mTOR activation is common in GYN. Predictive biomarkers to PAMi in GYN have yet to be identified. Methods: Advanced GYN pts with available genomic data, treated with PAMi in phase I/II clinical trials were selected. Mutation (mut) allele fractions (MAFs) were corrected for tumor purity and defined as clonal (cl) (≥ 0.4) or subclonal (scl) ( 〈 0.4). PAMi efficacy: (i) time to progression (TTP); (ii) clinical benefit rate (CBR: complete/partial response or stable disease 〉 4 months [m]); and (iii) ratio TTP on PAMi/ TTP on non-standard chemotherapy pre- or post-PAMi (PAMi/nsChemo TTP). Results: From 2010 to 2016, 264 GYN pts (152 ovarian(OC); 75 endometrial(EC); 37 cervical(CC)) had genomic analysis; 50 pts (24 OC [11 PIK3CA mut, 5 KRAS mut] , 15 EC [6 PIK3CA mut, 5 PTEN mut, 4 KRAS mut], and 11 CC [9 PIK3CA mut, 3 KRAS mut] ) received PAMi (17 pan-PI3K/mTOR or AKT inh, 17 α-PI3K inh, 16 PAMi targeted combos). PAMi therapy was matched (MA) to PIK3CA/PTEN mut in 30 pts (60%). Median age was 57 years (30-70); median number of prior lines was 2 (1-6) and 34 pts (68%) received nsChemo. Efficacy of PAMi: (i) median TTP (3.27 m [95% CI 2.1-4.4] with trend for longer TTP in OC compared to others [3.93 vs. 2.1 m, HR 0.57; p = 0.08] , without differences according to MA status [p = 0.26] or regimen [p = 0.5] ); (ii) CBR (42% [95% CI 27-58%], without differences according to tumor type [p = 0.47] , MA status [p = 1] or regimen [p = 0.86] ); and (iii) TTP PAMi/nsChemo ≥ 1.3 (42% [95% CI 24-63%], without differences according to tumor type [p = 0.53] , MA status [p = 0.23] or regimen [p = 0.41] ). Partial responses were seen in 5 pts (4 PIK3CA mut on single agent PAMi; 1 KRAS mut on PI3K + MEK inh). Of 4 KRAS mut pts, none had CBR with single agent PAMi. PIK3CA mut were cl in 63% of OC, 17% of EC and 40% of CC. Clonal exon 20 PIK3CA mut were more frequent in OC (p = 0.03). We found longer TTP for cl PIK3CA events (4.0 vs. 1.5 m in scl, HR 5.1, p = 0.006) and a trend for exon 20 events (4.4 vs. 1.4 m in exon 9, HR 1.7, p = 0.25). Conclusions: Regardless of PIK3CA/PTEN mut status, PAMi confer CBR in almost 40% of GYN pts. Functionality and clonality of PIK3CA mut impact on TTP and interact with tumor type. Coexisting KRAS mut may drive resistance to single agent PAMi.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.5569
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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