BRCA1 mutation

Castration-Resistant Prostate Carcinoma

Predictive

Supports Sensitivity Response

accepted

EID11203

This randomized, open-label, phase 3 trial evaluated the PARP inhibitor olaparib in 387 men with metastatic castration-resistant prostate cancer (mCRPC) who had disease progression while receiving a n… (full text at CIViC)

PMID 32343890 · de Bono et al., 2020 · Open in CIViC

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Malignant NeoplasmALIAS

Predictive

Supports Sensitivity Response

accepted

EID1370

In this phase 1 trial, 60 patients with advanced solid tumors (ovarian, breast, colorectal, melanoma, sarcoma, prostate) were treated with PARP inhibitor olaparib. Durable antitumor activity was only … (full text at CIViC)

PMID 19553641 · Fong et al., 2009 · Open in CIViC

〃

Predictive

Supports Sensitivity Response

accepted

EID7274

In the phase 3 SOLO1 trial 390 patients with newly diagnosed advanced ovarian cancer with a mutation in BRCA1 or BRCA2 who had complete or partial response after platinum-based chemotherapy were rando… (full text at CIViC)

PMID 30345884 · Moore et al., 2018 · Open in CIViC

〃

Predictive

Supports Sensitivity Response

accepted

EID7275

PMID 30345884 · Moore et al., 2018 · Open in CIViC

〃

Predictive

Supports Sensitivity Response

accepted

EID1772

In a study of 63 patients with ovarian cancer, 17 patients had BRCA1 or BRCA2 mutations and 46 patients had no BRCA mutations. Of the BRCA-positive patients, 7/17(41%; 95%CI 22-64) showed objective r… (full text at CIViC)

PMID 21862407 · Gelmon et al., 2011 · Open in CIViC

Cediranib + OlaparibCombination

Predictive

Supports Sensitivity Response

accepted

EID1677

46 women with platinum-sensitive, high-grade, BRCA1/2+ ovarian cancer received either olaparib monotherapy or olaparib/cediranib combination therapy. Median PFS was increased in combination therapy (… (full text at CIViC)

PMID 25218906 · Liu et al., 2014 · Open in CIViC

Rucaparib

Predictive

Supports Sensitivity Response

accepted

EID11136

Combined meta-analysis of Study 10 (NCT01482715, phase I/II) and ARIEL2 (NCT01891344, phase II), both multi-centre, open-label, single-arm trials evaluating rucaparib in ovarian cancer with BRCA1 or B… (full text at CIViC)

PMID 28882436 · Oza et al., 2017 · Open in CIViC

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Predictive

Supports Sensitivity Response

accepted

EID11138

PMID 28882436 · Oza et al., 2017 · Open in CIViC

〃

Predictive

Supports Sensitivity Response

accepted

EID1897

A phase 2 trial on patients with relapsed, platinum-sensitive high grade ovarian, fallopian tube or primary peritoneal carcinoma (ARIEL2 Part1, NCT01891344) was held to assess PARP inhibitor rucaparib… (full text at CIViC)

PMID 27908594 · Swisher et al., 2017 · Open in CIViC

〃

Predictive

Supports Sensitivity Response

accepted

EID6341

PMID 27908594 · Swisher et al., 2017 · Open in CIViC

Cisplatin + OxaliplatinSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID5915

Patients with BRCA1/2 associated pancreatic adenocarcinoma were evaluated retrospectively. In patients with stage 3 and 4, the median overall survival (mOS) was 22 months for the platinum exposed (n=2… (full text at CIViC)

PMID 25072261 · Golan et al., 2014 · Open in CIViC

Predictive

Supports Sensitivity Response

accepted

EID5914

Twenty-three patients with pancreatic cancer havoring BRCA1/2 germline mutations received olaparib. Five (21.7%) patients had a BRCA1 mutation. All but one had received prior gemcitabine, and 65% had … (full text at CIViC)

PMID 25366685 · Kaufman et al., 2015 · Open in CIViC

Veliparib

Predictive

Does Not Support Sensitivity Response

accepted

EID5934

Veliparib 400mg BID was administered to patients with germline BRCA1/2-mutated pancreatic cancer. Sixteen patients were enrolled. All except two (12.5%) had previously been treated with platinum thera… (full text at CIViC)

PMID 29223478 · Lowery et al., 2018 · Open in CIViC

Cisplatin + Gemcitabine + VeliparibCombination

Predictive

Supports Sensitivity Response

accepted

EID5932

In Phase I study for pancreatic cancer patients GEM 600 mg/m2 + CDDP 25 mg/m2 + Veliparib 20 - 80 mg twice daily showed response rate of 77.8% (7/9) and mOS of 23.3 months in germline BRCA mutation-p… (full text at CIViC)

PMID 29338080 · O'Reilly et al., 2018 · Open in CIViC

Platinum Compound

Ovarian Carcinoma

Predictive

Supports Sensitivity Response

accepted

EID1529

In a study of ovarian carcinomas, 81% of tumors with germline BRCA1/2 mutations were platinum sensitive, whereas only 60% of tumors with non-BRCA1/2 mutations were platinum sensitive (N=47; N=158; P=0… (full text at CIViC)

PMID 24240112 · Pennington et al., 2014 · Open in CIViC

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Ovarian Carcinoma

Predictive

Supports Sensitivity Response

accepted

EID1531

In a study of ovarian carcinomas, 87% of tumors with somatic BRCA1/2 mutations were platinum sensitive, whereas only 60% of tumors with non-BRCA1/2 mutations were platinum sensitive (N=38; N=158; P=0.… (full text at CIViC)

PMID 24240112 · Pennington et al., 2014 · Open in CIViC

Carboplatin + CisplatinSubstitutes

Triple-Negative Breast CarcinomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID1684

In an evaluation of 77 patients, those who had BRCA1/2 germline mutations (n=11) had an increase response rate to cisplatin when compared to those without germline mutations (54.5% versus 19.7%; P=0.0… (full text at CIViC)

PMID 25847936 · Isakoff et al., 2015 · Open in CIViC

Triple-Negative Breast CarcinomaALIAS

Predictive

Supports Resistance

accepted

EID1775

In a study of 26 patients with breast cancer, 10 patients were BRCA-positive and 16 patients were BRCA-negative. Regardless of BRCA status, none showed objective response when treated with olaparib.

PMID 21862407 · Gelmon et al., 2011 · Open in CIViC

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HER2 Negative Breast CancerUNRESOLVED

Predictive

Supports Sensitivity Response

accepted

EID5830

Randomized, open-label, phase 3 trial in which olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation HER2–negative metastatic breast cancer. 205 patients we… (full text at CIViC)

PMID 28792849 · 2017 · Open in CIViC

Malignant Breast Neoplasm

BRCA1 Loss-of-function9
Pidnarulex + QuarfloxinSubstitutes	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	4	accepted	EID1924 The authors show that in the CX-5461 and CX-3543, G-quadruplex stabilizing agents, demonstrate specific toxicity against BRCA deficient breast cancer derived cells and polyclonal patient-derived xenog… (full text at CIViC) PMID 28211448 · Xu et al., 2017 · Open in CIViC	civic
Talazoparib	Malignant Breast Neoplasm	Predictive	B	Supports Sensitivity Response	4	accepted	EID4838 In part 2 of a two-part dose-escalation phase I trial (NCT01286987), 71 patients with Ewings sarcoma, breast, ovarian, small cell lung, or pancreatic cancers received 1.0 mg/day talazoparib treatment.… (full text at CIViC) PMID 28242752 · de Bono et al., 2017 · Open in CIViC	civic
Olaparib	Malignant Ovarian Neoplasm	Predictive	B	Supports Sensitivity Response	4	accepted	EID211 The combination of PARP inhibition (Olaparib) with BRCA mutation results in irreparable and lethal DNA damage. Response rates are higher in BRCA1 mutation positive women with high grade serous or undi… (full text at CIViC) PMID 23346317 · Goff, 2013 · Open in CIViC	civic
Talazoparib	Malignant Ovarian Neoplasm	Predictive	B	Supports Sensitivity Response	3	accepted	EID4876 In part 2 of a two-part dose-escalation phase I trial (NCT01286987), 71 patients with Ewings sarcoma, breast, ovarian, small cell lung, or pancreatic cancers received 1.0 mg/day talazoparib treatment.… (full text at CIViC) PMID 28242752 · de Bono et al., 2017 · Open in CIViC	civic
Olaparib	Malignant Prostate Neoplasm	Predictive	C	Supports Sensitivity Response	2	accepted	EID845 1/1 patients with BRCA1 homozygous deletion had a response to olaparib in this phase 2 study. PMID 26510020 · Mateo et al., 2015 · Open in CIViC	civic
〃	Pancreatic Adenocarcinoma	Predictive	A	Supports Sensitivity Response	5	accepted	EID7384 In the phase 3 POLO trial patients who had germline BRCA1/2 mutation and metastatic pancreatic adenocarcinoma that had not progressed during first-line platinum-based chemotherapy were allocated to ma… (full text at CIViC) PMID 31157963 · Golan et al., 2019 · Open in CIViC	civic
〃	Triple-Negative Breast CarcinomaALIAS	Predictive	A	Supports Sensitivity Response	5	accepted	EID11216 Report of OlympiA (NCT02032823), a randomized, double-blind, placebo-controlled study of 1836 patients with HER2-negative breast cancer with germline pathogenic or likely pathogenic mutations in BRCA1… (full text at CIViC) PMID 34081848 · Tutt et al., 2021 · Open in CIViC	civic
〃	HER2 Negative Breast CancerUNRESOLVED	Predictive	A	Supports Sensitivity Response	5	accepted	EID11201 Report of OlympiA (NCT02032823), a randomized, double-blind, placebo-controlled study of 1836 patients with HER2-negative breast cancer with germline pathogenic or likely pathogenic mutations in BRCA1… (full text at CIViC) PMID 34081848 · Tutt et al., 2021 · Open in CIViC	civic
〃	HER2 Negative Breast CancerUNRESOLVED	Predictive	B	Supports Sensitivity Response	5	accepted	EID5815 302 patients (234 with progression events) with HER2-negative metastatic breast cancer and with a confirmed deleterious or suspected deleterious germline BRCA mutation (164 BRCA1, 129 BRCA2) had signi… (full text at CIViC) PMID 28578601 · Robson et al., 2017 · Open in CIViC	civic

BRCA1 Loss-of-function9

Pidnarulex + QuarfloxinSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID1924

The authors show that in the CX-5461 and CX-3543, G-quadruplex stabilizing agents, demonstrate specific toxicity against BRCA deficient breast cancer derived cells and polyclonal patient-derived xenog… (full text at CIViC)

PMID 28211448 · Xu et al., 2017 · Open in CIViC

Malignant Breast Neoplasm

Talazoparib

Predictive

Supports Sensitivity Response

accepted

EID4838

In part 2 of a two-part dose-escalation phase I trial (NCT01286987), 71 patients with Ewings sarcoma, breast, ovarian, small cell lung, or pancreatic cancers received 1.0 mg/day talazoparib treatment.… (full text at CIViC)

PMID 28242752 · de Bono et al., 2017 · Open in CIViC

Predictive

Supports Sensitivity Response

accepted

EID211

The combination of PARP inhibition (Olaparib) with BRCA mutation results in irreparable and lethal DNA damage. Response rates are higher in BRCA1 mutation positive women with high grade serous or undi… (full text at CIViC)

PMID 23346317 · Goff, 2013 · Open in CIViC

Talazoparib

Predictive

Supports Sensitivity Response

accepted

EID4876

PMID 28242752 · de Bono et al., 2017 · Open in CIViC

Malignant Prostate Neoplasm

Predictive

Supports Sensitivity Response

accepted

EID845

1/1 patients with BRCA1 homozygous deletion had a response to olaparib in this phase 2 study.

PMID 26510020 · Mateo et al., 2015 · Open in CIViC

Pancreatic Adenocarcinoma

〃

Predictive

Supports Sensitivity Response

accepted

EID7384

In the phase 3 POLO trial patients who had germline BRCA1/2 mutation and metastatic pancreatic adenocarcinoma that had not progressed during first-line platinum-based chemotherapy were allocated to ma… (full text at CIViC)

PMID 31157963 · Golan et al., 2019 · Open in CIViC

〃

Triple-Negative Breast CarcinomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID11216

Report of OlympiA (NCT02032823), a randomized, double-blind, placebo-controlled study of 1836 patients with HER2-negative breast cancer with germline pathogenic or likely pathogenic mutations in BRCA1… (full text at CIViC)

PMID 34081848 · Tutt et al., 2021 · Open in CIViC

〃

HER2 Negative Breast CancerUNRESOLVED

Predictive

Supports Sensitivity Response

accepted

EID11201

PMID 34081848 · Tutt et al., 2021 · Open in CIViC

〃

HER2 Negative Breast CancerUNRESOLVED

Predictive

Supports Sensitivity Response

accepted

EID5815

302 patients (234 with progression events) with HER2-negative metastatic breast cancer and with a confirmed deleterious or suspected deleterious germline BRCA mutation (164 BRCA1, 129 BRCA2) had signi… (full text at CIViC)

PMID 28578601 · Robson et al., 2017 · Open in CIViC

BAP1 Loss-of-function + BRCA1 Loss-of-functionBRCA1 BAP11
Rucaparib	Malignant Mesothelioma	Predictive	B	Supports Sensitivity Response	3	accepted	EID11739 In this phase 2a clinical trial, 26 patients with either BRCA1-deficient or BAP1-deficient mesotheliomas were treated with Rucaparib. 38% of the patients were BAP1 and BRCA1 negative, 89% were BAP1 ne… (full text at CIViC) PMID 33515503 · Fennell et al., 2021 · Open in CIViC	civic

BAP1 Loss-of-function + BRCA1 Loss-of-functionBRCA1 BAP11

Rucaparib

Malignant Mesothelioma

Predictive

Supports Sensitivity Response

accepted

EID11739

In this phase 2a clinical trial, 26 patients with either BRCA1-deficient or BAP1-deficient mesotheliomas were treated with Rucaparib. 38% of the patients were BAP1 and BRCA1 negative, 89% were BAP1 ne… (full text at CIViC)

PMID 33515503 · Fennell et al., 2021 · Open in CIViC

BRCA1 Expression1
Vinorelbine	Malignant Mesothelioma	Predictive	D	Supports Sensitivity Response	2	accepted	EID933 Expression of BRCA1 in 6 mesothelioma cell lines was associated with sensitivity to vinorelbine in functional studies. PMID 22190288 · Busacca et al., 2012 · Open in CIViC	civic

BRCA1 Expression1

Vinorelbine

Malignant Mesothelioma

Predictive

Supports Sensitivity Response

accepted

EID933

Expression of BRCA1 in 6 mesothelioma cell lines was associated with sensitivity to vinorelbine in functional studies.

PMID 22190288 · Busacca et al., 2012 · Open in CIViC

BRCA1 Underexpression1
Platinum Compound + Taxane CompoundCombination	Malignant Ovarian Neoplasm	Predictive	B	Supports Sensitivity Response	3	accepted	EID942 Absent/low expression of BRCA1 (IHC) was associated with improved response to chemotherapy in 292 patients with sporadic ovarian cancer compared to patients with high expression (odds ratio 2.47: 95%C… (full text at CIViC) PMID 21920589 · Carser et al., 2011 · Open in CIViC	civic

BRCA1 Underexpression1

Platinum Compound + Taxane CompoundCombination

Predictive

Supports Sensitivity Response

accepted

EID942

Absent/low expression of BRCA1 (IHC) was associated with improved response to chemotherapy in 292 patients with sporadic ovarian cancer compared to patients with high expression (odds ratio 2.47: 95%C… (full text at CIViC)

PMID 21920589 · Carser et al., 2011 · Open in CIViC

BRCA1 Q1467*1

Rucaparib

Predictive

Supports Sensitivity Response

—

accepted

EID2878

In a phase 2 study of 206 recurrent, platinum-sensitive, high-grade ovarian cancer patients, patients with germline or somatic BRCA1 or BRCA2 mutation (n=40) were associated with improved progression … (full text at CIViC)

PMID 27908594 · Swisher et al., 2017 · Open in CIViC

BRCA1 W1815X1

Ovarian Endometrioid AdenocarcinomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID4623

In an in vitro study, a SNU-251 cell line expressing BRCA1 W1815X truncating mutation demonstrated increased sensitivity to olaparib treatment with long-term exposure, compared to ovarian cell lines e… (full text at CIViC)

PMID 23415752 · Stordal et al., 2013 · Open in CIViC