Pazopanib and Everolimus combination and PIK3CA alterations
Journal Name: Investigational New drugs
Phase I Combination of Pazopanib and Everolimus in PIK3CA Mutation Positive/PTEN Loss Patients with Advanced Solid Tumors Refractory to Standard Therapy
Heloisa Veasey Rodrigues1,Danxia Ke2, JoAnn Lim2, Bettzy Stephen2, Jorge Bellido2, Filip Janku2 , Ralph Zinner2, Apostolia Tsimberidou2, David Hong2, Sarina Piha-Paul2, Siqing Fu2, Aung Naing2, Vivek Subbiah2, Daniel Karp2, Gerald Falchook3, Razelle Kurzrock4, Jennifer Wheler2
1 Centro de Oncologia e Hematologia do Hospital Israelita Albert Einstein, São Paulo, Brazil; 2 Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, 3 Sarah Cannon Research Institute at HealthONE, Denver, CO; 4 Department of Medicine, University of California, San Diego, La Jolla, CA.
Corresponding Author:Jennifer J. Wheler, MD, The University of Texas MD Anderson Cancer Center, Department of Investigational Cancer Therapeutics, Unit 455, 1400 Holcombe Boulevard, Houston, TX 77030; Phone: (713) 745-9246; Fax: (713) 563-0566; Email:
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Pazopanib and Everolimus combination and PIK3CA alterations
Supplementary Table 1. Characteristics of patients with PI3K/AKT/mTOR pathway alterations
Case No. / Cancer Diagnosis / Molecular Test / PIK3CA mutation / PTEN mutation / PTEN loss(IHC) / Other PI3K-mTOR aberrations / Other aberrations / Best response(% change)
22 / Colorectal / NGSb / - / - / Yes / RICTOR amplification / APC N659fs*14, K1449fs*24;
AURKA amplification / 11
27 / Rectal / 46 gene panelc / - / - / Yes / - / MET T1010I;
SMAD4 R361C;
TP53 G245S;
c-KIT M541L / 4
54 / Colorectal / NGSb / Q546K / - / No / - / KRAS G13D;
CTNNB1 T41A V22_T41del;
PTPRD S1845fs*2;
TP53 R248W / NA
60 / Colorectal / 46 gene panelc / H1047R / - / No / - / KRAS G12V / - 10
49 / Breast / 46 gene panelc / - / - / Yes / - / APC P870S;
TP53 V157F2 / NA
50 / Breast
ER+ PR- HER2 - / 46 gene panelc / - / - / Yes / - / ABL1 G254R;
NRAS Q61H;
TP53 R213* / 0
58 / Breast / 46 gene panelc and NGSb / H1047R / - / No / - / FGFR3 amplification;
CCND1 amplification;
TP53 R249M / -20
61 / Breast
ER+ PR- HER2 - / 46 gene panelc and NGSb / H1047R / - / No / - / ATM R337C;
ARID1A P111fs*250, Y148fs*1;
MAP3K1 Q345*;
PALB2 N280fs*3;
MYST3 amplification;
ZNF703 amplification / -34
62 / Breast / 46 gene panelc / H1047R / - / No / - / JAK3 S568* / NA
9 / Ovarian / Single gene assessment / - / - / Yes / - / - / 14
28 / Vaginal / 46 gene panelc and NGSb / E45K / - / No / - / STK11 loss;
PTPRD S1845fs*2 / -38
4 / Endometrial / Single gene assessment / - / - / Yes / - / - / 42
44 / Endometrial / SequenomR platformd / - / - / Yes / - / - / 3
53 / Endometrial / NGSb / H1047R / Q17* / No / AKT3 amplification;
PIK3R1 T350fs*23 / KRAS G12D;
MCL1 amplification;
ARID1A H203fs*196 / -20
56 / Cervical / NGSb / E545K / - / No / - / PTPN11 S502L / NA
57 / Cervical / 46 gene panelc and NGSb / E542K / - / No / - / c-KIT variant M541L;
TOP1 amplification;
SRC amplification;
AURKA amplification;
ARFRP1 amplification;
ZNF217 amplification / -2
59 / Endocervical / 46 gene panelc and NGSb / E545K / Yes / - / EGFR G796S;
FGFR3-TACC3 fusion and amplification / 0
5 / Non-small cell lung cancer / 46 gene panelc / - / - / Yes / - / KRAS G12V / -6
7 / Pecoma / Single gene assessment / - / - / Yes / - / - / 11
35 / Clear cell sarcoma / NGSb / - / - / Yes / - / CDKN2A/B loss;
TP53 T284P, R248Q / 0
52 / Leiomyosarcoma / NGSb / - / - / Yes / - / RB1 loss / -9
55 / Leiomyosarcoma / NGSb / - / - / Yes / - / TP53 217V_218VinsVPYEPPE / -1
32 / Salivary gland / SequenomR platformd / - / - / No / AKT1 E17K / NRAS Q61R / 41
33 / Hepatocellular carcinoma / NGSb / H1047R / - / No / - / CTNNB1 S37C;
PTPRD 1845fs*2 / 8
16 / Hepatocellular carcinoma / NGSb / - / - / No / NF1 R1241* / BAP1 truncation, exon 12; CTNNB1 N387K / -30
48 / Small cell bladder / NGSb / - / - / No / AKT1 E17K;
RICTOR amplification / TP53 R248W;
KDM6A splice site 3209+1G>A;
RB1 Q62* / NA
a NA: not accessible for RECIST restaging.
bNGS: Next Generation Sequencing – Foundation Medicine®.
c46 gene panel: MDACC gene panel for solid tumors
dKnightDiagnostic Laboratories®
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