Pilot clinical trial and phenotypic analysis in chemotherapy-pretreated, metastatic triple-negative breast cancer patients treated with oral TAK-228 and TAK-117 (PIKTOR) to increase DNA damage repair deficiency followed by cisplatin and nab paclitaxel

Lang, Jessica D.; Nguyen, Tuong Vi V.; Levin, Maren K.; Blas, Page E.; Williams, Heather L.; Rodriguez, Esther San Roman; Briones, Natalia; Mueller, Claudius; Selleck, William; Moore, Sarah; Zismann, Victoria L.; Hendricks, William P.D.; Espina, Virginia; O’Shaughnessy, Joyce

doi:10.1186/s40364-023-00511-7

Table 1 Patient demographics and tumor characteristics

From: Pilot clinical trial and phenotypic analysis in chemotherapy-pretreated, metastatic triple-negative breast cancer patients treated with oral TAK-228 and TAK-117 (PIKTOR) to increase DNA damage repair deficiency followed by cisplatin and nab paclitaxel

Patients								Biomarkers	Treatment on Study			Post-Study Treatment
Patient ID	Age at Study Entry	Ethnicity	Sites of Metastatic Disease	Prior Therapies (neo/adjuvant)	Prior Therapies (metastatic)	Pre-PIKTOR Biopsy Site	Post-PIKTOR Biopsy Site	Standard of Care Germline Tumor/Blood NGS and IHC Results	Total weeks on PIKTOR	Total Weeks on Cis/Nab Pac	Response to Cis/Nab Pac	Treatment	Duration (weeks)
001	40	White	Internal mammary LN, abdominal LN, bone, brain	Cisplatin Docetaxel + Cyclophosphamide	Gemcitabine + Carploplatin Xeloda	Inguinal LN	Same as pre-PIKTOR site	G: BRCA1 +; BRCA2 -	7	16	SD	Pembrolizumab	106
								S: NOTCH1; TP53; MYC; FGFR2; CIC Amplification of PDGFRA
								IHC: PD-L1 Negative; 22C3: PD-L1 Negative
002	57	White	Chest wall, mediastinal LN, lung	Doxorubicin + Cyclophosphamide + Paclitaxel Carboplatin + Capecitabine	N/A	Lung	Axillary LN	G: BRCA1/2 -	9	3	PD	Entrectinib	5
002	57	White	Chest wall, mediastinal LN, lung		N/A	Lung	Axillary LN	S: TP53; MYO5A NTRK3; PAK1; CDKN2A; CDKN2B Amplification of C11ORF30 (EMSY); PIK3CA	9	3	PD	Entrectinib	5
004	38	White	Mediastinum LN, lung	Doxorubicin + Cyclophosphamide + Paclitaxel Carboplatin Capecitabine	N/A	Cervical LN	Supraclavicular LN	G: Panel Germline Testing Negative	10	17	PR	Paclitaxel + Bevacizumab + Pembrolizumab	18
								S: PTEN; LZTR1; NOTCH2; TP53; AR; FGFR1; PIK3CA; MET MTAP; ARID2 Amplification of ZNF217; PIK3CA; RAF1; KRAS; CCND2; CCND1; MET; BRAF; FGFR2; PDGFRA; KIT; CDK6; CCNE1
								IHC: PD-L1 Negative
005	58	White	Axilla LN, lung	Doxorubicin + Cyclophosphamide + Paclitaxel	N/A	Lung	Same as pre-PIKTOR site	G: BRCA1 +; other Panel Germline Testing Negative	5	9	PD	Eribulin + Pembrolizumab	11
								S: TP53
								PD-L1 Negative
006	68	White	Internal mammary LN, supraclavicular LN	Doxorubicin + Cyclophosphamide + Paclitaxel Carboplatin + Capecitabine	Letrozole + Xeloda Faslodex + Palbociclib	Supraclavicular LN	Same as pre-PIKTOR site	G: BRCA1/2 -; MUTYH	11	6	PD	Pembrolizumab	190
								S: TP53; INPP4B; MLL3; MEF2B; Amplification of CDK4
								IHC: PD-L1 Positive
008	39	African American	Axillary LN, supraclavicular LN, thoracic LN, internal mammary LN	Doxorubicin + Cyclophosphamide Carboplatin + Paclitaxel	Gemcitabine + Carboplatin	Axillary LN	Same as pre-PIKTOR site	G: Panel Germline Testing Negative	14	18	SD	Pembrolizumab	65
								S: PIK3CA; TP53; RB1;
								IHC: P-L1 Negative, CPS 10, 22C3; PD-L1 Positive, CPS 11, 22C3
009	48	White, Hispanic/ Latino	Lung, mediastinal LN	Docetaxel + Cyclophosphamide	N/A	Lung	Same as pre-PIKTOR site	G: Panel Germline Testing Negative	4	7	PD	Pembrolizumab	12
								S: PTEN; TP53; RB1; MLL2; CREBBP; MLL3 Amplification of FGFR1; PIK3CA; CCNE1; MYC
								IHC: PD-L1 Negative
010	63	White,	Supraclavicular LN, mediastinal LN, hilar LN	Doxorubicin + Cyclophosphamide + Paclitaxel	Taxol	Supraclavicular LN	Same as pre-PIKTOR site	G: Unknown	14	17	SD	N/A	N/A
								S: TP53; BAP1; PTEN; ETV6;
								IHC: PD-L1 Negative
011	42	Asian	Supraclavicular LN	Epirubicin + Docetaxel	Niraparib PARP inhibitor clinical trial Carboplatin + Gemzar Eribulin	Supraclavicular LN	Same as pre-PIKTOR site	G: BRCA1 +; other Panel Germline Testing Negative	7	3	PD	Paclitaxel + Bevacizumab + Capecitabine	5
								S: TP53; TCF7L2; INPP4B; BAP1 Amplification of FGFR2; MYC
								IHC: PD-L1 Negative
012	51	White	Paratracheal LN, lung	Doxorubicin + Cyclophosphamide + Paclitaxel	Carboplatin, Gemcitabine Abraxane + Tecentriq Pembrolizumab	Lung	Same as pre-PIKTOR site	G: Panel Germline Testing Negative	3	6	PD	Erubilin	7
012	51	White	Paratracheal LN, lung	Doxorubicin + Cyclophosphamide + Paclitaxel	Carboplatin, Gemcitabine Abraxane + Tecentriq Pembrolizumab	Lung	Same as pre-PIKTOR site	S: TP53	3	6	PD	Erubilin	7

Abbreviations: LN = lymph node; N/A = not applicable; PD = progression of disease; PR = partial response; SD = stable disease; Cis = Cisplatin; Nab Pac = Nab-Paclitaxel; G = Germline Mutations; S: Somatic Mutations; VUS: Variance of Unknown Significance; IHC = Immunohistochemistry; NGS = Next-generation sequencing;
Footnote: Patients 003 and 007 were screen fails and did not receive treatment; Patients 001 and 006 are still alive, Patient 001 is on currently on bevacizumab and Patient 006 is currently on pembrolizumab

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ISSN: 2050-7771

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