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Ref Type Journal Article
PMID (32343890)
Authors de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M
Title Olaparib for Metastatic Castration-Resistant Prostate Cancer.
URL
Abstract Text Multiple loss-of-function alterations in genes that are involved in DNA repair, including homologous recombination repair, are associated with response to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition in patients with prostate and other cancers.We conducted a randomized, open-label, phase 3 trial evaluating the PARP inhibitor olaparib in men with metastatic castration-resistant prostate cancer who had disease progression while receiving a new hormonal agent (e.g., enzalutamide or abiraterone). All the men had a qualifying alteration in prespecified genes with a direct or indirect role in homologous recombination repair. Cohort A (245 patients) had at least one alteration in BRCA1, BRCA2, or ATM; cohort B (142 patients) had alterations in any of 12 other prespecified genes, prospectively and centrally determined from tumor tissue. Patients were randomly assigned (in a 2:1 ratio) to receive olaparib or the physician's choice of enzalutamide or abiraterone (control). The primary end point was imaging-based progression-free survival in cohort A according to blinded independent central review.In cohort A, imaging-based progression-free survival was significantly longer in the olaparib group than in the control group (median, 7.4 months vs. 3.6 months; hazard ratio for progression or death, 0.34; 95% confidence interval, 0.25 to 0.47; P<0.001); a significant benefit was also observed with respect to the confirmed objective response rate and the time to pain progression. The median overall survival in cohort A was 18.5 months in the olaparib group and 15.1 months in the control group; 81% of the patients in the control group who had progression crossed over to receive olaparib. A significant benefit for olaparib was also seen for imaging-based progression-free survival in the overall population (cohorts A and B). Anemia and nausea were the main toxic effects in patients who received olaparib.In men with metastatic castration-resistant prostate cancer who had disease progression while receiving enzalutamide or abiraterone and who had alterations in genes with a role in homologous recombination repair, olaparib was associated with longer progression-free survival and better measures of response and patient-reported end points than either enzalutamide or abiraterone. (Funded by AstraZeneca and Merck Sharp & Dohme; PROfound ClinicalTrials.gov number, NCT02987543.).

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Molecular Profile Treatment Approach
ATM C1674Y Olaparib
RAD54L P85A Olaparib
ATM C2488Y Olaparib
ATM C2021Y Olaparib
CHEK2 E351K Olaparib
ATM G2695C Olaparib
BRIP1 S614Y Olaparib
ATM S1455R Olaparib
RAD54L Q90* Olaparib
BRIP1 E726* Olaparib
ATM E2977Rfs*2 Olaparib
BARD1 E287* Olaparib
RAD51C Q143R Olaparib
BRIP1 R173C Olaparib
CHEK2 Y390S Olaparib
CHEK2 W93Gfs*17 Olaparib
ATM L1764I Olaparib
RAD51C G162Efs*9 Olaparib
ATM G2919D Olaparib
ATM A416E Olaparib
ATM E1724K Olaparib
RAD54L inact mut Olaparib
ATM Q1500* Olaparib
ATM E1666* Olaparib
RAD51B inact mut Olaparib
CHEK2 I189V Olaparib
ATM R2459S Olaparib
CHEK2 K287fs Olaparib
ATM R2993* Olaparib
ATM V2757M Olaparib
RAD51C Q133E Olaparib
ATM E668* Olaparib
CHEK2 D409N Olaparib
FANCL T367Nfs*13 Olaparib
ATM H2125L Olaparib
ATM P1680R Olaparib
ATM W164C Olaparib
BARD1 Y180fs Olaparib
ATM K1030* Olaparib
BRIP1 W335L Olaparib
CHEK2 P85L Olaparib
BRIP1 N576Kfs*2 Olaparib
ATM R1618* Olaparib
CHEK2 A392P Olaparib
CHEK2 C108R Olaparib
ATM Q2730P Olaparib
CHEK2 M381* Olaparib
RAD54L S49E Olaparib
ATM L100W Olaparib
CHEK2 E239K Olaparib
BRIP1 inact mut Olaparib
CHEK2 V198Ffs*7 Olaparib
ATM Q2177* Olaparib
ATM Y1229* Olaparib
ATM Y2371* Olaparib
ATM R2912Efs*26 Olaparib
CHEK2 R148G Olaparib
BRIP1 G49R Olaparib
ATM T2934N Olaparib
PALB2 N344Tfs*2 PARP Inhibitor (Pan)
CHEK2 I157T Olaparib
CHEK2 K253* Olaparib
ATM E2304Gfs*69 Olaparib
ATM L233* Olaparib
ATM V2951F Olaparib
BRIP1 L860P Olaparib
ATM G197E Olaparib
ATM E2295* Olaparib
CHEK2 L183F Olaparib
BARD1 V154fs Olaparib
ATM W2960L Olaparib
CHEK2 G370E Olaparib
BRIP1 C832Y Olaparib
ATM S1403fs Olaparib
BARD1 D135N Olaparib
ATM D2870Y Olaparib
BARD1 R406* Olaparib
ATM G2020D Olaparib
CHEK2 H143Y Olaparib
ATM D2016H Olaparib
ATM E2904Q Olaparib
ATM E2768* Olaparib
ATM A2843D Olaparib
CHEK2 S357F Olaparib
ATM R2763* Olaparib
RAD54L F82S Olaparib
ATM T2682I Olaparib
RAD54L L381Cfs*8 Olaparib
ATM E2039G Olaparib
ATM S1905Ifs*25 Olaparib
ATM S2017fs Olaparib
ATM E2096* Olaparib
RAD54L K189R Olaparib
ATM N3033* Olaparib
CDK12 Q944* Olaparib
ATM P2759L Olaparib
ATM Q1015* Olaparib
ATM W308* Olaparib
ATM Q2762* Olaparib
ATM N2326_K2363del Olaparib
ATM L2427_R2428del Olaparib
ATM E1342* Olaparib
BRIP1 K52R Olaparib
ATM P2829S Olaparib
ATM Q2733* Olaparib
ATM T2853R Olaparib
ATM N1719D Olaparib
CDK12 G909R Olaparib
ATM L1078P Olaparib
ATM Q1640* Olaparib
RAD51D E157* Olaparib
ATM V2937G Olaparib
ATM L2780R Olaparib
ATM I1453fs Olaparib
ATM L2659S Olaparib
ATM A2308V Olaparib
ATM V1268* Olaparib
CHEK2 K224E Olaparib
ATM H2554D Olaparib
ATM G2072E Olaparib
CDK12 A88fs Olaparib
CDK12 Y319fs Olaparib
ATM A2602E Olaparib
BRIP1 Q227* Olaparib
ATM L2767R Olaparib
ATM P1379R Olaparib
ATM S2549fs Olaparib
CHEK1 inact mut Olaparib
BARD1 C53W Olaparib
CHEK2 L236P Olaparib
ATM P1829R Olaparib
RAD51C G150E Olaparib
ATM G2477* Olaparib
BRIP1 Q689* Olaparib
ATM G2020C Olaparib
CHEK2 T476M Olaparib
ATM R2598* Olaparib
ATM L1936S Olaparib
BRIP1 R865W Olaparib
PALB2 K1098* PARP Inhibitor (Pan)
CHEK2 R181C Olaparib
CHEK2 Q209* Olaparib
ATM K2413Q Olaparib
BRIP1 L347P Olaparib
ATM F2393S Olaparib
BRIP1 G49* Olaparib
ATM I2948F Olaparib
ATM S853* Olaparib
ATM E1707* Olaparib
ATM S2190* Olaparib
BARD1 L44R Olaparib
ATM R2832C Olaparib
CDK12 S133Kfs*24 Olaparib
ATM R1730* Olaparib
BRIP1 E501* Olaparib
CHEK2 K249R Olaparib
ATM K468Efs*18 Olaparib
ATM F2839L Olaparib
RAD51B L103* Olaparib
CDK12 Q602* Olaparib
CHEK2 del Olaparib
BRIP1 R261* Olaparib
ATM L2427R Olaparib
ATM Q2637* Olaparib
CHEK2 E87* Olaparib
CDK12 W719* Olaparib
ATM W2769R Olaparib
CHEK2 T367fs Olaparib
CDK12 F89Sfs*3 Olaparib
BARD1 G681fs Olaparib
CHEK2 Q10fs Olaparib
ATM Q675* Olaparib
RAD51C G125V Olaparib
RAD51C R237P Olaparib
ATM E2977* Olaparib
RAD51C D159A Olaparib
ATM S719* Olaparib
CDK12 E928fs Olaparib
BRIP1 S624* Olaparib
ATM Y332H Olaparib
CHEK2 H143R Olaparib
CHEK2 G14Afs*47 Olaparib
ATM D2448G Olaparib
ATM Q2637E Olaparib
ATM V2823F Olaparib
BARD1 del Olaparib
ATM F2732V Olaparib
ATM F1025L Olaparib
BARD1 V767fs Olaparib
BRIP1 C283S Olaparib
ATM E958* Olaparib
ATM W164* Olaparib
ATM Q1970* Olaparib
ATM L2890I Olaparib
BARD1 W34R Olaparib
CHEK2 T476K Olaparib
RAD51C R214C Olaparib
PALB2 K346Tfs*13 PARP Inhibitor (Pan)
CHEK2 F202fs Olaparib
ATM S2761Vfs*41 Olaparib
RAD51D G112A Olaparib
ATM L442P Olaparib
CHEK2 E394K Olaparib
CHEK2 H345Y Olaparib
ATM G2891S Olaparib
ATM K293* Olaparib
ATM del Olaparib
ATM K241* Olaparib
ATM R1917G Olaparib
RAD51D loss Olaparib
ATM Y1961C Olaparib
ATM F2686C Olaparib
FANCL T367fs Olaparib
ATM W3055* Olaparib
ATM P2759S Olaparib
ATM E2444K Olaparib
RAD51C D108G Olaparib
ATM I2683M Olaparib
RAD51C G130A Olaparib
CHEK2 E64K Olaparib
ATM Q1636Rfs*10 Olaparib
BRIP1 I983fs Olaparib
CHEK2 M304T Olaparib
ATM Q2972* Olaparib
BRIP1 Y461* Olaparib
RAD51C C135R Olaparib
ATM L1874F Olaparib
RAD51C S163R Olaparib
RAD51C A155E Olaparib
ATM F2393I Olaparib
ATM Q1310* Olaparib
ATM L2452P Olaparib
ATM S214Pfs*16 Olaparib
ATM Q1531* Olaparib
ATM M1755I Olaparib
ATM M1628V Olaparib
ATM Y2969* Olaparib
ATM Q781* Olaparib
ATM G335E Olaparib
CHEK2 S372Y Olaparib
ATM K2440N Olaparib
ATM C2337R Olaparib
RAD51C E80* Olaparib
ATM R250Sfs*3 Olaparib
ATM L1078R Olaparib
BARD1 G700Afs*14 Olaparib
ATM C2349F Olaparib
CHEK2 E161del Olaparib
CDK12 S62fs Olaparib
CHEK2 H54Pfs*6 Olaparib
BRIP1 S913fs Olaparib
ATM R2060H Olaparib
ATM E1072* Olaparib
ATM L2623F Olaparib
ATM T2947S Olaparib
CHEK2 E107_K197del Olaparib
ATM R2060C Olaparib
ATM L419* Olaparib
BARD1 G753D Olaparib
ATM E1892* Olaparib
ATM S1599* Olaparib
RAD51C T102I Olaparib
ATM E277* Olaparib
BRIP1 N541fs Olaparib
ATM D2448A Olaparib
ATM G2695V Olaparib
CDK12 H111fs Olaparib
BRIP1 L392* Olaparib
ATM Y2833D Olaparib
ATM R1466P Olaparib
RAD51B Y46* Olaparib
ATM L2338P Olaparib
CHEK2 R318H Olaparib
ATM G2083* Olaparib
RAD51C Q133K Olaparib
ATM D2016G Olaparib
ATM E2187* Olaparib
ATM A2635D Olaparib
ATM R2486* Olaparib
CHEK2 Y424H Olaparib
ATM N2875T Olaparib
ATM Q2220* Olaparib
ATM L2445P Olaparib
CDK12 K1021* Olaparib
ATM G2869C Olaparib
CHEK2 Y390C Olaparib
ATM K331E Olaparib
ATM L2868F Olaparib
ATM L1255* Olaparib
CDK12 R882L Olaparib
ATM Q1117* Olaparib
ATM W3052L Olaparib
RAD51C R312W Olaparib
ATM G2063V Olaparib
ATM W2300L Olaparib
ATM L2946S Olaparib
ATM V1941F Olaparib
BRIP1 R848H Olaparib
BARD1 C645R Olaparib
RAD51C E146* Olaparib
ATM R76* Olaparib
ATM C907* Olaparib
ATM D2016N Olaparib
BRIP1 L415P Olaparib
ATM S421* Olaparib
ATM L2051P Olaparib
ATM G2695S Olaparib
ATM E968* Olaparib
ATM S1455Vfs*3 Olaparib
ATM Q284* Olaparib
ATM P1288Q Olaparib
RAD51C G114V Olaparib
ATM F2571Yfs*4 Olaparib
ATM dec exp Olaparib
BRIP1 del Olaparib
ATM S1487* Olaparib
ATM E2164K Olaparib
ATM I2629fs Olaparib
ATM R2034* Olaparib
RAD51D D206A Olaparib
ATM L145R Olaparib
ATM C2931Y Olaparib
ATM W524* Olaparib
BRIP1 L358P Olaparib
RAD51B R8* Olaparib
ATM Q1906* Olaparib
RAD51C V140E Olaparib
ATM W1058C Olaparib
ATM T1200Lfs*7 Olaparib
ATM G3030V Olaparib
ATM Q628Pfs*7 Olaparib
ATM Y731* Olaparib
ATM R250* Olaparib
ATM S83L Olaparib
RAD51C inact mut Olaparib
ATM N2494Y Olaparib
ATM N2632K Olaparib
CDK12 K756R Olaparib
ATM W57* Olaparib
ATM K2749I Olaparib
ATM P960H Olaparib
RAD51C L27P Olaparib
ATM R2973M Olaparib
CDK12 T212fs Olaparib
ATM L1562* Olaparib
CDK12 Y279* Olaparib
ATM L2952P Olaparib
ATM G3030E Olaparib
ATM E1346* Olaparib
ATM Q501* Olaparib
ATM E3022* Olaparib
ATM K1057* Olaparib
RAD51D V203E Olaparib
CHEK2 Y139* Olaparib
CHEK2 N185fs Olaparib
CHEK2 T366fs Olaparib
ATM Y1938C Olaparib
ATM F1767V Olaparib
CHEK2 T387S Olaparib
BARD1 Q730* Olaparib
CHEK2 K373E Olaparib
ATM G2024W Olaparib
ATM Y2080C Olaparib
BARD1 D612fs Olaparib
ATM V2664del Olaparib
ATM E1978* Olaparib
ATM Q2730R Olaparib
BRIP1 T997fs Olaparib
ATM E2895A Olaparib
CHEK2 D162G Olaparib
CHEK2 K135Nfs*26 Olaparib
BARD1 V523A Olaparib
CHEK2 H371Y Olaparib
ATM W3055L Olaparib
ATM W1710* Olaparib
ATM I2702M Olaparib
CHEK2 N352D Olaparib
ATM R3047* Olaparib
ATM V723G Olaparib
RAD51C S105* Olaparib
RAD51C D159Y Olaparib
ATM K1807E Olaparib
CHEK2 L309P Olaparib
CHEK2 E149Ifs*6 Olaparib
BRIP1 E81* Olaparib
CHEK2 S428F Olaparib
BARD1 K209Efs*5 Olaparib
ATM N2501S Olaparib
ATM H2075L Olaparib
ATM A2626V Olaparib
ATM V2951D Olaparib
ATM D2913Y Olaparib
ATM negative Olaparib
ATM L2427P Olaparib
ATM Y2627C Olaparib
ATM E2014K Olaparib
RAD51C loss Olaparib
ATM Q91* Olaparib
PALB2 inact mut PARP Inhibitor (Pan)
ATM Q401* Olaparib
ATM V1678G Olaparib
ATM Q684* Olaparib
ATM Q654Rfs*10 Olaparib
ATM S83* Olaparib
ATM R2506_N2543del Olaparib
ATM Q2297* Olaparib
CHEK2 E275* Olaparib
ATM I2076S Olaparib
ATM E2539* Olaparib
ATM S2407* Olaparib
FANCL T224K Olaparib
BRIP1 R439* Olaparib
ATM L1239fs Olaparib
ATM L1524R Olaparib
ATM A59S Olaparib
CHEK2 R117A Olaparib
BRIP1 G224* Olaparib
ATM R329T Olaparib
RAD54L E297* Olaparib
PALB2 N821Tfs*25 PARP Inhibitor (Pan)
ATM G3051E Olaparib
ATM E2052K Olaparib
ATM I1849fs Olaparib
ATM G3030R Olaparib
ATM D2085H Olaparib
ATM E2014G Olaparib
ATM K2431* Olaparib
ATM S2855_V2856delinsRI Olaparib
RAD54L del Olaparib
ATM R2723* Olaparib
ATM G1746R Olaparib
CHEK2 R382* Olaparib
ATM P955S Olaparib
PALB2 W898* PARP Inhibitor (Pan)
CDK12 D877N Olaparib
BRIP1 A349P Olaparib
ATM E2126* Olaparib
ATM V278fs Olaparib
CHEK2 G306A Olaparib
ATM C540* Olaparib
BARD1 G623E Olaparib
BRIP1 Q554Hfs*35 Olaparib
BARD1 N295S Olaparib
ATM L745* Olaparib
BRIP1 R836* Olaparib
PALB2 Q1056* PARP Inhibitor (Pan)
ATM L2447W Olaparib
BRIP1 R762P Olaparib
ATM W1058* Olaparib
BRIP1 S990A Olaparib
ATM L1465P Olaparib
ATM S2592C Olaparib
ATM Y1442* Olaparib
ATM L2945M Olaparib
BRIP1 V341D Olaparib
ATM G294* Olaparib
BRIP1 L340R Olaparib
CHEK2 R180H Olaparib
ATM R1304* Olaparib
ATM W2960C Olaparib
CHEK2 C284Y Olaparib
BARD1 Q564H Olaparib
ATM R1466G Olaparib
ATM V1941L Olaparib
BRIP1 Y147* Olaparib
PALB2 R1086Efs*9 PARP Inhibitor (Pan)
RAD51D K91Ifs*13 Olaparib
ATM L2953Tfs*3 Olaparib
BRIP1 E795* Olaparib
CDK12 R271* Olaparib
ATM V2757E Olaparib
ATM T554M Olaparib
BRIP1 loss Olaparib
CHEK2 P426R Olaparib
ATM G2072R Olaparib
CDK12 inact mut Olaparib
ATM H2788Y Olaparib
CHEK2 loss Olaparib
CHEK2 F169Lfs*2 Olaparib
ATM E739* Olaparib
ATM L15fs Olaparib
ATM T2947N Olaparib
CHEK2 F125S Olaparib
ATM L427* Olaparib
ATM L2715R Olaparib
ATM K2747N Olaparib
BARD1 L465F Olaparib
ATM A2622V Olaparib
BRIP1 Q561* Olaparib
BARD1 T719R Olaparib
RAD51B loss Olaparib
BRIP1 I504fs Olaparib
ATM G1202* Olaparib
ATM A2524P Olaparib
ATM R2459P Olaparib
BARD1 inact mut Olaparib
ATM R447* Olaparib
ATM P2353R Olaparib
CHEK1 del Olaparib
ATM S2859Y Olaparib
ATM L2780I Olaparib
RAD51C R366Q Olaparib
ATM Q2641* Olaparib
ATM D2720Y Olaparib
ATM V2424G Olaparib
ATM L2952V Olaparib
ATM L944R Olaparib
CHEK2 T323P Olaparib
ATM L2492F Olaparib
ATM K2237* Olaparib
ATM V519I Olaparib
RAD51C L226P Olaparib
RAD54L Y309* Olaparib
ATM A2067V Olaparib
CHEK2 R95* Olaparib
ATM E390* Olaparib
BRIP1 Y408Lfs*14 Olaparib
ATM I1581Nfs*5 Olaparib
ATM I2876F Olaparib
ATM E522* Olaparib
ATM L2952I Olaparib
ATM L2738* Olaparib
PALB2 S979Vfs*11 PARP Inhibitor (Pan)
ATM W2042L Olaparib
ATM H2125Y Olaparib
RAD51C T132R Olaparib
RAD51C T132P Olaparib
ATM R2461P Olaparib
CHEK1 R379* Olaparib
ATM R248Q Olaparib
CHEK2 R474C Olaparib
ATM A2062V Olaparib
CHEK2 W93R Olaparib
BRIP1 T48Qfs*7 Olaparib
BARD1 C71Y Olaparib
ATM V2441D Olaparib
CHEK2 L326P Olaparib
ATM E2621* Olaparib
ATM R2642I Olaparib
BARD1 C83R Olaparib
BRIP1 Q126* Olaparib
ATM C353fs Olaparib
RAD51C L265* Olaparib
PALB2 loss PARP Inhibitor (Pan)
CHEK2 R145W Olaparib
ATM W3052C Olaparib
ATM C1674R Olaparib
ATM C2770G Olaparib
ATM L2572fs Olaparib
ATM E2676* Olaparib
ATM R2790S Olaparib
ATM D1637N Olaparib
ATM D2870N Olaparib
ATM E2039K Olaparib
CDK12 R701* Olaparib
ATM Q2066R Olaparib
ATM G330V Olaparib
RAD51C V140G Olaparib
RAD51C R258H Olaparib
ATM E2444D Olaparib
ATM R2929K Olaparib
ATM S2489F Olaparib
ATM A2067D Olaparib
ATM L1176fs Olaparib
ATM K2363N Olaparib
CHEK2 D293fs Olaparib
ATM Y2852C Olaparib
ATM Q2651* Olaparib
ATM E518fs Olaparib
ATM Q445* Olaparib
RAD51D V200* Olaparib
ATM Y1216* Olaparib
ATM G2765V Olaparib
CDK12 S343fs Olaparib
ATM W2109* Olaparib
BRIP1 K998Efs*60 Olaparib
ATM E2932K Olaparib
RAD51D E37* Olaparib
CDK12 P335fs Olaparib
ATM G1746E Olaparib
BRIP1 Q25* Olaparib
ATM R2032K Olaparib
ATM F2827C Olaparib
CDK12 E1024* Olaparib
RAD51C R12W Olaparib
CDK12 K46fs Olaparib
CHEK2 A230P Olaparib
ATM Q2066H Olaparib
ATM Q1171Tfs*8 Olaparib
BRIP1 C283R Olaparib
FANCL I336_C337delinsS Olaparib
ATM K331N Olaparib
BARD1 P187A Olaparib
ATM E2744* Olaparib
ATM S214fs Olaparib
ATM G2765A Olaparib
ATM R2854L Olaparib
ATM R1882* Olaparib
CHEK2 Q34Vfs*42 Olaparib
ATM V2716A Olaparib
ATM R2849* Olaparib
ATM Q14* Olaparib
ATM W412* Olaparib
ATM R2105S Olaparib
ATM Q2414* Olaparib
ATM E2837K Olaparib
RAD51C L219S Olaparib
RAD51D S207L Olaparib
CHEK2 A237T Olaparib
PALB2 N1039Ifs*2 PARP Inhibitor (Pan)
CHEK2 L216* Olaparib
ATM E2294Q Olaparib
ATM S1993Rfs*23 Olaparib
CDK12 L122* Olaparib
ATM T2333Nfs*40 Olaparib
ATM inact mut Olaparib
ATM Q1579fs Olaparib
ATM R2453P Olaparib
ATM R2151K Olaparib
ATM Q2740* Olaparib
CHEK2 E273K Olaparib
ATM M946I Olaparib
ATM L436P Olaparib
ATM P292L Olaparib
BRIP1 D393V Olaparib
BARD1 loss Olaparib
CDK12 R204fs Olaparib
CDK12 L996F Olaparib
ATM W2769* Olaparib
BARD1 S551* Olaparib
ATM L100* Olaparib
ATM V2288fs Olaparib
BARD1 K312N Olaparib
ATM R2263* Olaparib
ATM C458Y Olaparib
ATM R2871K Olaparib
BARD1 Q730L Olaparib
ATM H1380Y Olaparib
CHEK2 D438Y Olaparib
ATM G330* Olaparib
CHEK2 A247D Olaparib
ATM W2845C Olaparib
ATM G2891D Olaparib
ATM E836* Olaparib
CHEK2 T59K Olaparib
FANCL inact mut Olaparib
ATM R2849P Olaparib
BARD1 S660R Olaparib
CDK12 P683Qfs*70 Olaparib
BRIP1 C283H Olaparib
ATM T2902fs Olaparib
ATM G2867R Olaparib
ATM K742* Olaparib
ATM S131* Olaparib
CDK12 S785fs Olaparib
PALB2 L35F PARP Inhibitor (Pan)
BRIP1 P785L Olaparib
BRIP1 K703Ifs*3 Olaparib
RAD51C del Olaparib
ATM V2906A Olaparib
ATM L991* Olaparib
BRIP1 P991A Olaparib
CHEK2 D265_H282del Olaparib
ATM E3015* Olaparib
ATM Q2028* Olaparib
BRIP1 S653* Olaparib
RAD51D inact mut Olaparib
ATM L2345F Olaparib
ATM R2580* Olaparib
ATM E2164D Olaparib
PALB2 L24F PARP Inhibitor (Pan)
CHEK2 S412R Olaparib
BARD1 V85M Olaparib
ATM W2960* Olaparib
CHEK2 C385R Olaparib
FANCL M247V Olaparib
BARD1 Q564* Olaparib
ATM R1875* Olaparib
ATM E2272* Olaparib
BRIP1 G51* Olaparib
ATM F2732L Olaparib
PALB2 G808* PARP Inhibitor (Pan)
PALB2 E1010* PARP Inhibitor (Pan)
ATM T1743I Olaparib
ATM V2862F Olaparib
ATM R2138Kfs*8 Olaparib
ATM C2735F Olaparib
ATM Q2277* Olaparib
ATM I2701Nfs*17 Olaparib
ATM P2907H Olaparib
ATM R2912T Olaparib
BRIP1 F366S Olaparib
RAD51D G96C Olaparib
ATM V1538fs Olaparib
ATM D1053N Olaparib
ATM A2346T Olaparib
ATM Q2269* Olaparib
BRIP1 Q815* Olaparib
ATM S601I Olaparib
ATM V2830D Olaparib
ATM G2765S Olaparib
ATM L762Qfs*4 Olaparib
CHEK2 R406Vfs*8 Olaparib
BRIP1 G690E Olaparib
ATM G1676fs Olaparib
BRIP1 V676E Olaparib
RAD51D Q41* Olaparib
CHEK2 D347N Olaparib
ATM A2602fs Olaparib
ATM Q2522fs Olaparib
ATM L2447F Olaparib
CHEK2 C420T Olaparib
BRIP1 W448* Olaparib
ATM Q1709* Olaparib
ATM L2890R Olaparib
PALB2 S254Ifs*3 PARP Inhibitor (Pan)
ATM C2931W Olaparib
CHEK2 L183S Olaparib
ATM Y2437* Olaparib
ATM V1268fs Olaparib
ATM L1322P Olaparib
ATM L2850F Olaparib
ATM W2483* Olaparib
BRIP1 R831K Olaparib
ATM R2227C Olaparib
ATM K2756* Olaparib
ATM G2536* Olaparib
BRIP1 G763C Olaparib
ATM W412L Olaparib
CHEK2 R474H Olaparib
CHEK2 Y220C Olaparib
ATM S2685* Olaparib
ATM L1956H Olaparib
CHEK2 E321* Olaparib
FANCL D306* Olaparib
CHEK2 T410fs Olaparib
ATM Y1938H Olaparib
ATM L1449* Olaparib
ATM G2891C Olaparib
RAD51C V156D Olaparib
CDK12 K975E Olaparib
ATM Q1627* Olaparib
BRIP1 R798* Olaparib
BRIP1 R581* Olaparib
ATM S712* Olaparib
CHEK2 G167R Olaparib
CDK12 Y901C Olaparib
CDK12 G879V Olaparib
ATM I2683T Olaparib
ATM T1953A Olaparib
RAD54L K189A Olaparib
BRIP1 Q645* Olaparib
ATM G2922V Olaparib
ATM G2867E Olaparib
ATM V2892G Olaparib
ATM S978fs Olaparib
ATM T2934I Olaparib
ATM H2872D Olaparib
ATM L1718V Olaparib
ATM V2951I Olaparib
ATM P2974L Olaparib
BRIP1 R279Q Olaparib
BRIP1 E387* Olaparib
RAD51D G107V Olaparib
PALB2 Q1023* PARP Inhibitor (Pan)
ATM R1898* Olaparib
ATM R1466* Olaparib
BRIP1 S697P Olaparib
BRIP1 C350F Olaparib
ATM R2105W Olaparib
ATM S751* Olaparib
ATM P604S Olaparib
ATM Y54* Olaparib
ATM M1484Rfs*15 Olaparib
PALB2 R414* PARP Inhibitor (Pan)
ATM C353R Olaparib
ATM T2666I Olaparib
ATM L1348W Olaparib
ATM P2793T Olaparib
ATM K1410* Olaparib
ATM Q513* Olaparib
RAD51D del Olaparib
ATM Q14P Olaparib
CHEK2 R117G Olaparib
BRIP1 S601* Olaparib
ATM R1095I Olaparib
ATM P2665S Olaparib
ATM D2708N Olaparib
ATM R337S Olaparib
ATM T2921M Olaparib
CHEK2 G229S Olaparib
ATM L2255I Olaparib
ATM Q1116* Olaparib
CHEK2 I160T Olaparib
BARD1 L480S Olaparib
CHEK2 A392S Olaparib
ATM R3008C Olaparib
ATM T2921R Olaparib
ATM V2892D Olaparib
RAD51C D348V Olaparib
ATM Q2724K Olaparib
ATM S2394L Olaparib
ATM E2181K Olaparib
CDK12 del Olaparib
ATM G2718_K2756del Olaparib
RAD51D K91fs Olaparib
ATM D2913H Olaparib
ATM H2125R Olaparib
CHEK2 P85R Olaparib
CHEK2 K244R Olaparib
ATM V2937A Olaparib
PALB2 del PARP Inhibitor (Pan)
CHEK2 R474L Olaparib
ATM A2626T Olaparib
ATM L2659* Olaparib
ATM G3051R Olaparib
CHEK2 D82_E86del Olaparib
ATM Q2066L Olaparib
CHEK2 I160M Olaparib
ATM S2685P Olaparib
FANCL Q18* Olaparib
CHEK2 E122Dfs*8 Olaparib
BARD1 Q164* Olaparib
BARD1 P707S Olaparib
RAD54L R75* Olaparib
RAD51C T287A Olaparib
ATM R2419* Olaparib
ATM K3053* Olaparib
BRIP1 G690R Olaparib
BRIP1 S189L Olaparib
CHEK2 G386R Olaparib
ATM S214Ffs*40 Olaparib
RAD51C K131I Olaparib
ATM D1637Y Olaparib
ATM L1647P Olaparib
ATM L2890P Olaparib
CHEK2 A392V Olaparib
ATM Q1537L Olaparib
PALB2 R170fs PARP Inhibitor (Pan)
ATM H2872R Olaparib
ATM A2787V Olaparib
RAD51C T121R Olaparib
CHEK2 E321K Olaparib
PALB2 K908fs PARP Inhibitor (Pan)
PALB2 T494Lfs*67 PARP Inhibitor (Pan)
ATM E73* Olaparib
BARD1 A460T Olaparib
ATM R3008H Olaparib
CHEK2 N290Ifs*15 Olaparib
ATM W2300* Olaparib
ATM K2440E Olaparib
BRIP1 R777C Olaparib
ATM Q2684* Olaparib
ATM K102* Olaparib
ATM A302fs Olaparib
BRIP1 Q685* Olaparib
ATM S677N Olaparib
PALB2 L947F PARP Inhibitor (Pan)
ATM W1058R Olaparib
ATM R2973W Olaparib
BRIP1 S772* Olaparib
RAD51B del Olaparib
ATM N81Tfs*20 Olaparib
ATM L2001S Olaparib
ATM D2448H Olaparib
ATM K468fs Olaparib
CDK12 V387* Olaparib
CDK12 E72fs Olaparib
ATM K2670* Olaparib
RAD51C R193* Olaparib
ATM V2119fs Olaparib
BARD1 P24fs Olaparib
CHEK2 N166S Olaparib
RAD51C A279P Olaparib
ATM K2811fs Olaparib
ATM Q2397* Olaparib
ATM D2448N Olaparib
ATM S1947P Olaparib
CHEK2 T367Mfs*15 Olaparib
ATM Q2730L Olaparib
ATM G3051V Olaparib
CDK12 E647Kfs*8 Olaparib
CHEK2 G306E Olaparib
ATM P1526L Olaparib
BARD1 G451fs Olaparib
ATM L2492R Olaparib
BRIP1 F993A Olaparib
ATM Q852* Olaparib
ATM Q1839* Olaparib
ATM G2925S Olaparib
CHEK2 S140N Olaparib
PALB2 Q790* PARP Inhibitor (Pan)
ATM E2039* Olaparib
ATM W2091* Olaparib
BRIP1 K752fs Olaparib
CHEK2 D347A Olaparib
ATM G2777D Olaparib
ATM L804fs Olaparib
BARD1 P530L Olaparib
ATM H2038Y Olaparib
ATM E2164G Olaparib
ATM V2926F Olaparib
ATM E343* Olaparib
CHEK2 S372F Olaparib
ATM D2959N Olaparib
ATM L2490F Olaparib
ATM W2638* Olaparib
FANCL R221W Olaparib
RAD51C L138F Olaparib
ATM R2973T Olaparib
ATM P2759H Olaparib
ATM P2829L Olaparib
BRIP1 P47A Olaparib
ATM R805* Olaparib
ATM Y2627* Olaparib
FANCL E217K Olaparib
ATM Y2755* Olaparib
ATM I1441fs Olaparib
BARD1 R565C Olaparib
RAD51C G153D Olaparib
ATM G1672V Olaparib
ATM E1979* Olaparib
ATM R1973I Olaparib
BRIP1 H396D Olaparib
CHEK2 F292fs Olaparib
ATM W3052* Olaparib
ATM S333F Olaparib
BRIP1 E626K Olaparib
ATM P2842L Olaparib
ATM R1917T Olaparib
ATM H2872Q Olaparib
ATM Y2627H Olaparib
ATM R248* Olaparib
BARD1 E652fs Olaparib
RAD54L E436* Olaparib
ATM R2526S Olaparib
ATM F2779C Olaparib
BRIP1 S805* Olaparib
ATM I352N Olaparib
ATM loss Olaparib
ATM G2919S Olaparib
ATM E2164Q Olaparib
ATM Q2800* Olaparib
ATM E2245* Olaparib
ATM Q446* Olaparib
ATM T2333fs Olaparib
BRIP1 S618* Olaparib
ATM P1069fs Olaparib
ATM G1522R Olaparib
ATM S2855R Olaparib
CHEK2 H483R Olaparib
ATM K1904* Olaparib
ATM T2666A Olaparib
CHEK2 G414E Olaparib
CHEK2 inact mut Olaparib
ATM E71* Olaparib
CHEK2 W485G Olaparib
CHEK2 F475Lfs*7 Olaparib
ATM N765Kfs*12 Olaparib
BARD1 P669L Olaparib
ATM D2720H Olaparib
ATM L1019P Olaparib
ATM W2104* Olaparib
ATM G2694E Olaparib
ATM K792N Olaparib
ATM D1682H Olaparib
ATM Y175* Olaparib
ATM S1993fs Olaparib
BARD1 G491R Olaparib
BRIP1 S697F Olaparib
ATM V566Ifs*6 Olaparib
ATM I10fs Olaparib
PALB2 K862Rfs*9 PARP Inhibitor (Pan)
ATM R2547_S2549del Olaparib
CHEK2 L174V Olaparib
ATM S1655F Olaparib
ATM E473* Olaparib
ATM S698* Olaparib
PALB2 H46Y PARP Inhibitor (Pan)
ATM Y2019C Olaparib
RAD51C C135Y Olaparib
BRIP1 T252R Olaparib
CDK12 loss Olaparib
CDK12 S587Ffs*54 Olaparib
ATM Q466* Olaparib
ATM Q3038* Olaparib
ATM G2765C Olaparib
ATM P2699L Olaparib
ATM R2691C Olaparib
BARD1 K321Nfs*21 Olaparib
BARD1 T598I Olaparib
BARD1 G698D Olaparib
CHEK2 I160R Olaparib
ATM R2854C Olaparib
ATM W2491C Olaparib
BARD1 G203* Olaparib
RAD54L loss Olaparib
ATM S2812Vfs*3 Olaparib
ATM L663* Olaparib
RAD51C G302V Olaparib
RAD51C F103V Olaparib
ATM Q2522H Olaparib
BARD1 S142* Olaparib
ATM S824F Olaparib
ATM G2897S Olaparib
ATM A2893P Olaparib
CHEK2 F169L Olaparib
CHEK2 S422Vfs*15 Olaparib
CHEK2 Q27* Olaparib
ATM M2520fs Olaparib
ATM A2893V Olaparib
CDK12 P58fs Olaparib
ATM V2951L Olaparib
ATM L2051R Olaparib
ATM L186* Olaparib
ATM I1294Nfs*8 Olaparib
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ATM R2227C prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM R2227C, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM R2547_S2549del prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM R2547_S2549del, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
RAD51B inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including RAD51B (PMID: 32343890; NCT02987543). detail... detail... 32343890
PALB2 inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including PALB2 (PMID: 32343890; NCT02987543). detail... detail... 32343890
ATM D2625_A2626delinsEP prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM D2625_A2626delinsEP, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). 32343890 detail... detail...
ATM D2708N prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM D2708N, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM R2032K prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM R2032K, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM F2827C prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM F2827C, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... detail... 32343890
ATM A2622V prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM A2622V, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... detail... 32343890
ATM G2765S prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM G2765S, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). 32343890 detail... detail...
RAD51C inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including RAD51C (PMID: 32343890; NCT02987543). detail... detail... 32343890
RAD51D inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including RAD51D (PMID: 32343890; NCT02987543). detail... detail... 32343890
CDK12 inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in metastatic castration-resistant prostate cancer patients harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, HR for progression or death was 0.74 in CDK12-mutant patients (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM R2832C prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM R2832C, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM Y2470D prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM Y2470D, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM A2067D prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM A2067D, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... detail... 32343890
ATM inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including nonsense, frameshift, rearrangement, splice site variants, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM R3008C prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM R3008C, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). 32343890 detail... detail...
ATM S2855_V2856delinsRI prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM S2855_V2856delinsRI, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). 32343890 detail... detail...
ATM V2716A prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM V2716A, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM R3008H prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM R3008H, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). 32343890 detail... detail...
BARD1 inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including BARD1 (PMID: 32343890; NCT02987543). detail... 32343890 detail...
ATM P292L prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM P292L, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
CHEK1 inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including CHEK1 (PMID: 32343890; NCT02987543). detail... detail... 32343890
BRIP1 inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including BRIP1 (PMID: 32343890; NCT02987543). detail... 32343890 detail...
CHEK2 inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in metastatic castration-resistant prostate cancer patients harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, HR for progression or death was 0.87 in CHEK2-mutant patients (PMID: 32343890; NCT02987543). detail... detail... 32343890
ATM D2016G prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM D2016G, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
RAD54L inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in metastatic castration-resistant prostate cancer patients harboring deleterious or suspected deleterious mutations in homologous recombination repair genes who progressed on hormone therapy, HR for progression or death was 0.33 in RAD54L-mutant patients (PMID: 32343890; NCT02987543). detail... detail... 32343890
ATM D2913Y prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) improved progression-free survival (7.4 vs 3.6 mo, HR 0.34, p<0.001), objective response rate (33% vs 2%, OR 20.86, p<0.001), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) over control in metastatic prostate cancer patients harboring inactivating BRCA/ATM mutations as detected by approved assays, including ATM D2913Y, HR was 1.04 in ATM-mutant group (PMID: 32343890; NCT02987543). detail... 32343890 detail...
FANCL inact mut prostate cancer sensitive Olaparib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including FANCL (PMID: 32343890; NCT02987543). detail... detail... 32343890