Supplemental Material

Supplemental Methods

1)Sequencing:

Hybridization-based capture of 3320 exons from 182 cancer-related genes and 37

introns of 14 genes commonly rearranged in cancer (previous version of the test performed

for nine patients) and 3769 exons from 236 cancer-related genes and 47 introns of 19

genes commonly rearranged in cancer (performed for 338 patients) was applied to ≥ 50 ng

of DNA extracted from 347 tumor specimens and sequenced to high, uniform coverage

with a mean sequencing depth of 714× as previously described35. Consistent median

sequencing depth was achieved by processing specimens according to optimized, locked

down, standard operating procedures (SOP) on automated liquid handlers in a Clinical

Laboratory Improvement Act (CLIA)-certified laboratory as previously described35. Genomic

alterations (base substitutions, small indels, rearrangements, copy number alterations)

were determined and then reported for these patient samples. Six or seven copy numbers

are reported as equivocal and > 8 are definitive; for ERBB2, equivocal amplification was 5

to 7 copies; all (equivocal or definitely amplified) were designated as positive for

amplification for this study).

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182 gene panel list:

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236 gene panel list:

ABL1 BTK CTNNB1 FGF23 IL7R MLH1 PDGFRA SMOAKT1 CARD11 DAXX FGF3 INHBA MLL PDGFRB SOCS1AKT2 CBFB DDR2 FGF4 IRF4 MLL2 PDK1 SOX10AKT3 CBL DNMT3A FGF6 IRS2 MPL PIK3CA SOX2ALK CCND1 DOT1L FGFR1 JAK1 MRE11A PIK3CG SPENAPC CCND2 EGFR FGFR2 JAK2 MSH2 PIK3R1 SPOPAR CCND3 EMSY

(C11orf30)FGFR3 JAK3 MSH6 PIK3R2 SRC

ARAF CCNE1 EP300 FGFR4 JUN MTOR PPP2R1A STAG2ARFRP1 CD79A EPHA3 FLT1 KAT6A

(MYST3)MUTYH PRDM1 STAT4

ARID1A CD79B EPHA5 FLT3 KDM5A MYC PRKAR1A STK11ARID2 CDC73 EPHB1 FLT4 KDM5C MYCL1 PRKDC SUFUASXL1 CDH1 ERBB2 FOXL2 KDM6A MYCN PTCH1 TET2ATM CDK12 ERBB3 GATA1 KDR MYD88 PTEN TGFBR2ATR CDK4 ERBB4 GATA2 KEAP1 NF1 PTPN11 TNFAIP3

ATRX CDK6 ERG GATA3 KIT NF2 RAD50 TNFRSF14AURKA CDK8 ESR1 GID4(C1

7orf39)KLHL6 NFE2L2 RAD51 TOP1

AURKB CDKN1B EZH2 GNA11 KRAS NFKBIA RAF1 TP53AXL CDKN2A FAM123B

(WTX)GNA13 LRP1B NKX2-1 RARA TSC1

BAP1 CDKN2B FAM46C GNAQ MAP2K1 NOTCH1 RB1 TSC2BARD1 CDKN2C FANCA GNAS MAP2K2 NOTCH2 RET TSHRBCL2 CEBPA FANCC GPR124 MAP2K4 NPM1 RICTOR VHL

BCL2L2 CHEK1 FANCD2 GRIN2A MAP3K1 NRAS RNF43 WISP3BCL6 CHEK2 FANCE GSK3B MCL1 NTRK1 RPTOR WT1BCOR CIC FANCF HGF MDM2 NTRK2 RUNX1 XPO1

BCORL1 CREBBP FANCG HRAS MDM4 NTRK3 SETD2 ZNF217BLM CRKL FANCL IDH1 MED12 NUP93 SF3B1 ZNF703

BRAF CRLF2 FBXW7 IDH2 MEF2B PAK3 SMAD2BRCA1 CSF1R FGF10 IGF1R MEN1 PALB2 SMAD4BRCA2 CTCF FGF14 IKBKE MET PAX5 SMARCA4BRIP1 CTNNA1 FGF19 IKZF1 MITF PBRM1 SMARCB1SELECT REARRANGEMENTS

ALK BCR BCL2 BRAF EGFR ETV1 ETV4 ETV5ETV6 EWSR1 MLL MYC NTRK1 PDGFRA RAF1 RARA

RET ROS1 TMPRSS2

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2)Therapy

Treatment was considered “matched” if at least one agent in the treatment regimen targeted at least one aberration or pathway component harbored in a patient’s molecular profile or a functionally active protein preferentially expressed in the tumor (e.g. estrogen receptor (ER) or HER2, assessed by standard of care testing other than NGS) with a half inhibitory concentration (IC50) in the low nM range. Examples of matched therapy included, but were not limited to: anti-EGFR drugs in the presence of EGFR anomalies, mTOR inhibitors for alterations in the PTEN/PIK3CA/Akt/mTOR pathway, BRAF or MEK inhibitors for RAF or RAS aberrations. More specifically, we defined “matched-direct” if at least one drug directly impacted the gene product of the molecular alteration or a differentially expressed protein [e.g. an EGFR inhibitor in a patient with an EGFR alteration (direct effect on the molecular aberration) or hormonal manipulation in patients with over-expressed estrogen or androgen receptors (proteins preferentially expressed on tumor cells were targeted)]. “Matched-indirect” was the term used for a drug that affects a target removed from the molecular aberration (e.g. mTOR inhibitor administered to patient with a PIK3CA mutation). Matched-direct therapy would include small molecule inhibitors with an IC50 ≤ 100 nM for the target, as well as antibodies whose primary target was the aberrant protein or a differentially expressed protein. Small molecule inhibitors that directly impacted a target, but had an 100 nM < IC50 ≤ 250 nM for that target were considered matched-indirect treatments. Matching designation was confirmed by the senior investigator (RK), who was blinded at the time of designation to the outcomes.

3)Matching ScoreIt is now well known that advanced tumors have multiple aberrations and that

combination therapy is likely to be better than monotherapy. Therefore, an exploratory scoring system (“Matching Score”) was developed that divided the number of matched drugs by the number of aberrations. Under this system, the higher the Matching Score, the better the match. The score for each match (direct or indirect) was assigned a 1; no match was a zero. If a drug directly impacted two targets present in the tumor, a 2 was given (example, a multikinase inhibitor with potent activity against more than one target present in a tumor); if two drugs each impacted a target directly in a patient, a 2 was also given. If two drugs were given that impacted directly (or indirectly) the same target in a patient, the number 2 was still given. The Matching Score was calculated by dividing the number derived from the direct and indirect matches in each tumor (numerator) by the number of aberrations (denominator). For instance, if a patient who tumor harbored six genomic aberrations received two drugs, the Matching Score would be 2/6 or 0.33. The cut-off of 0.2 for the OS analysis was chosen according to the minimum p-value criteria (Mazumdar and Glassman21).

4)Statistical Analysis 1. Patient’s characteristicsPatient characteristics were summarized using descriptive statistics. A diagram

displays the data availability for the matched and unmatched patients; patients who were lost to follow up or were still on prior therapy or on observation were considered unevaluable (see Figure 1).

2. Study endpoints and definitions4

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The following clinical endpoints were considered: (i) rate of [stable disease (SD)≥6 months/partial response (PR)/complete response (CR)]; (ii) progression-free survival (PFS) of the first line of therapy given after molecular profile results (PFS2); (iii) PFS2 versus PFS1 (immediate prior line of therapy), i.e., using patients as their own controls22,23; (iv) percent of patients with a PFS2/PFS1 ratio ≥ 1.322; and (v) overall survival (OS). SD, PR, or CR was determined per the assessment of the treating physician. PFS was defined as the time from the beginning of therapy to progression or the time to last follow up for patients that were progression-free (patients that were progression-free on the date of last follow up were censored on that date). OS was defined as the time from the beginning of therapy to death or last follow-up date for patients who were alive (the latter were censored on that date). The cut-off date for the analysis was April 1st 2015; all patients that were progression-free (for PFS) or alive (for OS) as of date of analysis were censored on that date unless their date of last follow up was earlier, in which case that was the date of censoring.

3. Analyses performedWhenever appropriate, Chi-Square tests were used to compare categorical

variables and the non-parametric Mann Whitney-U test to compare two groups on one continuous variable. Binary logistic regressions were performed for categorical endpoints. PFS and OS were analyzed by the Kaplan-Meier method24 and the log-rank test was used to compare variables. Cox regression models were used as multivariable analysis, when appropriate for survival endpoints. The importance of a prognostic factor was assessed by the Chi-Square and Wald-type test statistics (for the log-rank test and logistic regression/Cox regression models, respectively). The higher the Chi-square or Wald, the stronger the association.

3.1 Variables assessedThe main variables analyzed in this study were “matched versus unmatched”, the

primary diagnosis, the number of prior therapy lines (in advanced/metastatic setting), if the therapy was single agent or a combination, the total number of alterations, the presence of metastasis at diagnosis, the presence of metastasis at biopsy date (of tissue used for molecular testing).

3.2 Propensity score for being matched vs. notGiven the retrospective nature of our study, and to account for imbalances between

patients who were “matched” versus not, the “propensity” to receive a matched therapy for each patient was determined by using a multivariable logistic regression with “matched or not” as the outcome26–28. Variables included in the final propensity score model were “breast or not” cancers, “gastrointestinal or not” cancers, “skin/melanoma or not” cancers, “first line of treatment or not”, and “number of alterations”. This propensity score was used as a covariate in multivariable models or in the inverse probability of matched treatment weighting method. In the latter method, “matched” patients were given [1/Propensity score] as weight and “unmatched” patients were given [1/(1-Propensity score)] as weight. P-values were two-sided and considered significant if ≤0.05. Statistical analysis were performed by author MS with SPSS version 22.0.

Supplemental Table 1. Patient characteristics

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Characteristics Total patients, N=347

Age at diagnosis (years)(Median, CI 95%) 54 (52-55)

Gender Women Men

204 (59%)143 (41%)

Race Caucasian Other Asian African American Unknown Hispanic

247 (71.2%)46 (13.3%)26 (7.5%)13 (3.7%)9 (2.6%)6 (1.7%)

Type of cancer Gastro-intestinal Breast Brain Genitourinary Head and neck Lung Melanoma Othera

94 (27.1%)82 (23.7%)36 (10.4%)34 (9.8%)33 (9.5%)28 (8%)26 (7.5%)14 (4%)

aEwing sarcoma, carcinoid tumor, sarcomatoid tumor, peripheral nerve sheath tumor, pleiomorphic sarcoma (n=2), soft tissue rhabdomyosarcoma, leiomyosarcoma, and unknown origin (n=6).

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Supplemental Table 2. List of alterations and matched drugs

# Tumor type AlterationsMatched drug

(alteration(s) targeted bolded)

SD ≥ 6 months/PR/CR

1 Lung PTEN splice site 493-1 G>A everolimus YES

2 Breast EGFR amplification, CCND1 amplification, CDKN2A/B loss, FGFR1 amplification, MYC amplification, TP53 P151A

lapatinib YES

3 Breast ESR1a Y537S tamoxifen YES4 Head and neck PTEN I67K, CDKN2A/B loss, CTNNB1 T257I, MCL1 amplification everolimus NO

5 Head and neck ERBB2 amplification, FGFR4 amplification, NF1 loss, PIK3CA E545K, CCNE1 amplification, MYC amplification, TP53 D228fs*1

everolimus + lapatinib NO

6 GI FGFR2 amplification, CDKN2A loss, MYC amplification, APC I1307K, ARID1A P2139fs*62, TP53 F113C

ponatinib NO

7 GI APC S1421fs*52, APC A571fs*18, TP53 Y163C bevacizumab NO8 Brain EGFR amplification, CDKN2A loss lapatinib NO9 Breast ERBB2 amplification trastuzumab + lapatinib NO

10 Breast RET C634R, GATA3 P436fs*11+ sorafenib NO

11 Breast AKT3 amplification, MYC amplification, MYCL1 amplification, TP53 R248Q

everolimus NO

12 Breast ERBB2 amplification, MYC amplification, CDK6 amplification, TP53 R213*

trastuzumab YES

13 GI KRAS G13D, MYCL1 amplification, ATM R337C, DNMT3A R882H, TP53 G266R

bevacizumab YES

14 Skin/Melanoma BRAF V600E, MYC amplification, MSH6 R1068 dabrafenib NO

15 Breast ERBB2 amplification, PIK3CA H1047L, AURKA amplification, TP53 R342P, CREBBP P858S, ZNF217 amplification

trastuzumab + lapatinib + everolimus YES

16 Breast MCL1 amplification, ESR1a D538G letrozole NO17 GU FBXW7 E113D, MCL1 amplification, TP53 S241F bevacizumab YES

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18 GIAURKA amplification, CCND2 amplification, KRAS G12V, MYC A59V, RICTOR amplification, TP53 R248Q, FGF23 amplification, ZNF217 amplification

bevacizumab YES

19 Breast ERBB2 V777L, ERBB2 S1050*, FGFR1 amplification, PIK3CA E545K, TET2 S714*, TP53 W53*, ZNF703 amplification

trastuzumab + everolimus YES

20 GUNF1 Q1315*, NF1 Q2528fs*20, PTEN G44D, BRCA2 W993*, MLL R2204Q, TP53 G244S, TP53 S215G, KDM5C splice, MLH1 splice site 1558+1G>A, PBRM1 splice, SPEN splice

everolimus NO

21 Breast STK11 loss, TP53 R248W, MYC amplification, SMAD4 D415fs*14, GATA3 splice, MYST3 amplification

dasatinib NO

22 Breast PTEN N329fs*3, TP53 splice site 994-2A>G everolimus NO

23 BreastPIK3CA E545K, PTEN loss, MYC amplification, TP53 truncation intron 6, DNMT3A R882C, ASXL1 G181R, MAP3K1 C667fs*4, MAP3K1 H1058fs*24

everolimus NO

24 Breast PIK3CA H1047R, CCND1 amplification, ESR1a Y537S, KDM5C S717L, FGF19 amplification, FGF3 amplification, FGF4 amplification

everolimus + exemestane NO

25 BreastPIK3CA H1047R, ERBB2 amplification, TP53 Q317*, MYC amplification

T-DM1 YES

26 Head and neckBRAF V600E, PIK3CA Q546K

vemurafenib NO

27 Brain NF1 E2608*, PTEN H272fs*4, CDKN2A/B loss everolimus YES

28 BreastPIK3CA N345K, PTEN loss, CCND1 amplification, ARID1A F1728fs*4, NUP93 E14K, FGF19 amplification, FGF3 amplification, FGF4 amplification

everolimus YES

29 Head and neck PTCH1 Q853*, CDKN2A R80*, MDM2 amplification, TP53 R248Q, NOTCH1 E424K

vismodegib NO

30 Breast PIK3CA H1047R, MCL1 amplification,TP53 R156P, NFKBIA amplification, SF3B1 K700E

everolimus NO

31 BreastERBB2 amplification, FGFR1 amplification, FGFR2 amplification, PIK3CA H1047R, MCL1 amplification, MYC amplification, TP53 K132R, FANCA D1325fs*38, ZNF703 amplification

trastuzumab + pertuzumab YES

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32 Skin/Melanoma AKT1 E17K, FLT1 V395I sorafenib YES

33 BreastPTEN loss, CCND1 amplification, FGF19 amplification, FGF3 amplification, FGF4 amplification, GATA3 H435fs*9+, MEN1 R465*, ZNF703 amplification

everolimus NO

34 LungEGFR E746_A750del, AKT2 amplification, CDK6 amplification, TP53 K120fs*26, CCND1 amplification, CCNE1 amplification, CDKN2A/B loss, SMAD4 Y133fs*8, FGF19 amplification, FGF4 amplification, FGF3 amplification, AXL amplification, PBRM1 K416fs*3

erlotinib YES

35 Breast ERBB2 amplification, TP53 R248Q trastuzumab + lapatinib YES

36 BreastNF1 loss, PIK3CA E542K, CCND1 amplification, MCL1 amplification, TP53 splice site 993+1G>A, CDH1 P744fs*24, FGF19 amplification, FGF3 amplification, FGF4 amplification

everolimus NO

37 Lung RET KIF5B-RET fusion, MDM2 amplification cabozantinib NO38 Breast AKT1 E17K, NF1 Q2373*, KRAS A146V everolimus YES

39 Lung EGFR G719A, EGFR L861Q, MDM2 amplification, CDK4 amplification, GRIN2A R1022C

erlotinib YES

40 Breast PIK3CA E726K, PIK3CA H1047R everolimus YES41 Brain NF2 L117fs*6, RET V804M, CDKN2A/B loss, CDKN2C loss everolimus NO

42 BreastERBB2 amplification, FGFR1 amplification, TP53 I195T, NOTCH1 truncation exon 3, ARID1A A40fs*11, MAP3K1 Q390*, MYST3 amplification, ZNF703 amplification

trastuzumab YES

43 Breast ERBB2 amplification, MDM2 amplification, RUNX1 Y403fs*80+, EP300 P925T

trastuzumab NO

44 Breast ERBB2 amplification, SRC amplification, ARID1A E1019*, ARID1A E1108*, ZNF217 amplification, SPEN Q256*, GATA3 G335fs*16

T-DM1 + pertuzumab NO

45 Head and neck HRAS G13V, CDKN2A P114L, RICTOR amplification – equivocal⌘, TP53 P278R, FGF10 amplification – equivocal⌘ trametinib NO

46 Head and neckRET CCDC6-RET

vandetanib YES

47 Lung ALK EML4-ALK fusion, ARID2 A88fs*5 crizotinib NO48 GU JAK2 amplification ruxolitinib NO

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49 Brain EGFR amplification, EGFR vIII, IRS2 amplification, CDKN2A/B loss, CDKN2C L122fs*2, FANCA T1161M

erlotinib NO

50 BreastAKT1 E17K, CCND1 amplification-equivocal, ESR1a D538G, FGF3 amplification-equivocal, FGF4 amplification-equivocal, FGF19 amplification-equivocal

everolimus + exemestane NO

51 BreastERBB2 amplification – equivocal⌘, TSC1 truncation exon 7, PTPN11 E76K – subclonal⌘, TP53 R175H, BRIP1 duplication exons 15-17, BRIP1 amplification

trastuzumab + everolimus YES

52 Brain EGFR amplification, CDKN2A/B loss, MLL2 R4238C erlotinib NO

53 GU FBXW7 R465H, PIK3CA V344G, CCNE1 amplification, MYC amplification, TP53 R248W

bevacizumab NO

54 Breast RAF1 amplification, MYC amplification, TP53 E286G pazopanib YES

55 GUPIK3CA amplification, ERBB4 amplification – equivocal⌘, SOX2 amplification, MCL1 amplification – equivocal⌘, TP53 E258G, BRCA2 2417fs*4

MEK 162/BYL 719 trial (NCT01449058) YES

56 Breast

ERBB2 amplification, AKT3 amplification, JAK2 amplification – equivocal⌘, ATM R337H, TP53 R273L, MYC amplification, CDKN2A loss, ESR1 amplification – equivocal⌘, CDKN1B S56fs*15, CDK12 truncation

lapatinib NO

57 GU NF1 S821fs*5, TP53 S166*, MYC amplification, FANCC truncation exon 8

bevacizumab YES

58 GUKRAS G12D, PTEN R130G, ATR F1134fs*6, BRCA2 T3033fs*29, CTNNB1 D32N, NOTCH1 V1578del, ARID1A Q177fs*223, ARID1A D1850fs*33, AXL V289M, CTCF T204fs*18, LRP1B splice

MSC2363318A, a Dual p70S6K/Akt Inhibitor trial (NCT01971515)

NO

59 Breast IKBKE amplification everolimus NO60 Brain BRAF V600E, CDKN2A/B loss, CTNNA1 R731* vemurafenib YES61 Brain TP53 P278S, TP53 R249T, IDH1 R132S, ATRX N1232fs*15 bevacizumab NO

62 GI KRAS G13D, FBXW7 R13*, APC S1465fs*3, APC S559fs*2, MSH2 rearrangement exon 14, MAP2K4 loss

everolimus NO

63 Breast PIK3CA N345K, MYCN amplification, TP53 C277*, ARFRP1 amplification, ZNF217 amplification

everolimus NO

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64 Lung EGFR splice site 3272-1G>A, MET L903F, KRAS G12A, CCNE1 amplification, TP53 G154V, NFKBIA amplification – equivocal⌘ bevacizumab NO

65 Brain

KDR amplification – equivocal⌘, PDGFRA amplification – equivocal⌘, KIT amplification – equivocal⌘, JAK1 T593M, CDKN2A A36fs*17, TP53 R158H, TP53 R273H, NOTCH1 Q1049fs*130, NOTCH Q1687*, MSH2 Q395*, MSH6 K1358fs*2, SETD2 D2064fs*84, SPEN T3244fs*40, ATRX K358fs*2

bevacizumab NO

66 GI

EGFR amplification – equivocal⌘, GNAS amplification – equivocal⌘, PIK3CA E545K, AURKA amplification – equivocal⌘, CDK6 amplification, MYC amplification, TP53 R282W, CCND1 amplification, SMAD4 loss, FGF3 amplification, FGF4 amplification, FGF19 amplification, ZNF217 amplification – equivocal⌘, ARFRP1 amplification – equivocal⌘

bevacizumab YES

67 GU TP53 R273C bevacizumab NO

68 GI EGFR amplification, TP53 C176Y, APC R1435fs*38cetuximab and bevacizumab NO

69 Breast CCND1 amplification, MDM2 amplification, FGF3 amplification, FGF4 amplification, FGF19 amplification, GATA3 D336fs*17

palbociclib NO

70 GU KRAS G12V, CDKN2A E88*, MSH3 A60_A62del trametinib NO71 GI ERBB2 V777L, ERBB3 E928G, SMAD4 R361C lapatinib + trastuzumab NO

72 GUFGFR1 amplification – equivocal⌘, NF1 Q1218*, TP53 R267G, ERBB2 I767M, MLL2 P3668fs*5, MLL2 splice site 177-1G>T, ZNF703 amplification – equivocal⌘

pazopanib NO

73 Brain NF1 E318fs*11, PIK3CA R38H, PTEN loss, CDKN2A/B loss, TP53 E171fs*3, TP53 L194H, TP53 loss

bevacizumab NO

74 Lung

EGFR amplification – equivocal⌘, EGFR E746_A750del, EGFR T790M, AKT2 amplification – equivocal⌘, FGFR4 amplification, GNAS amplification – equivocal⌘, CCNE1 amplification, MCL1 amplification – equivocal⌘, TP53 E258K

EGFR inhibitor (clinical trial) NO

75 Breast PIK3CA amplification, SOX2 amplification, TP53 G302fs*42, FLT3 L260* faslodex for ER+ NO76 Breast AKT1 (E17K) casodex for AR+ NO77 Breast GATA3 *445fs*2+ tamoxifen for ER+ NO

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78 Breast CCND1 amplification, MCL1 amplification, CDH1 P127fs*89 faslodex for ER+ YES79 Breast MYC amplification, ARID1A R1461*, PALB2 G808fs*43, PALB2 Y1183* estradiol for ER+ NO

80 BreastTOP1 amplification, MYC amplification, AURKA amplification, TP53 R196P, MYST3 amplification, ZNF217 amplification, ZNF703 amplification

exemestane for ER+ NO

81 BreastFGFR1 amplification, CCND1 amplification, FGF19 amplification, FGF3 amplification, FGF4 amplification, MYST3 amplification, ZNF703 amplification

faslodex for ER+ YES

82 Breast PIK3CA H1047R, PIK3CA I1058L, CSF1R V32G arimidex for ER+ YES83 Breast IGF1R amplification, GATA3 M401fs*45+ exemestane for ER+ NO

84 Breast

SRC amplification, TOP1 amplification, MDM2 amplification, CCND1 amplification, CDK4 amplification, AURKA amplification, NKX2-1 amplification, NFKBIA amplification, ARID1A 253fs*111, FGF19 amplification, FGF3 amplification, FGF4 amplification, GATA3 G335fs*18, ZNF217 amplification

exemestane for ER+ NO

85 Breast

RPTOR amplification, CDKN2A/B loss, CCND1 amplification, TP53 H168R, SMAD4 loss, NKX2-1 amplification, BCL2L2 amplification, FGF19 amplification, FGF3 amplification, FGF4 amplification, GATA3 N332fs*21

letrozole for ER+ NO

86 Breast

AURKA amplification – equivocal⌘, CCND1 amplification, FGF3 amplification, FGF4 amplification, FGF19 amplification, MLL2 A4571T, EMSY amplification, ZNF217 amplification, ARFRP1 amplification – equivocal⌘

exemestane for ER+ NO

87 BreastPIK3CA H1047R, FGFR2 amplification

pertuzumab + trastuzumab for HER2+ NO

Abbreviations: GI: gastrointestinal; GU: genitourinary; ER+: estrogen receptor positive; HER2+: human epidermal growth factor receptor 2 positive; AR+: androgen receptor positive; SD ≥ 6 months or PR or CR: Stable disease ≥ 6 months or partial response or complete response of any duration. N=87 patients were matched; N=30/87 (34.5%) achieved SD ≥ 6 months/PR/CR. 13 of the 87 patients (15%, see patients number 75-87) were matched on basis of non-NGS marker only (these patients were considered matched as next-generation sequencing results were used in context of standard of care). aESR1 is generally a resistance mutation, but patients with such alterations may respond to certain hormonal modulators, depending on the mutation36(p1),37,38(p1)

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Supplemental Figure 1. Overall survival analysis

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Overall survival (Months)

Overall survival (Months)

Overall survival (Months)

A. “matched” versus “non-matched”

B. Matching-scores comparison

C. “responders” versus “non-responders”

Overall survival analysis (Kaplan Meier method). Refer to Table 3 for complete analysis. The P-value for the “matching-score” was P = 0.04 in a Cox regression model (backward conditional model).

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