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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 S1135_K1192del Olaparib
CHEK2 P85L Olaparib
ATM S1905Ifs*25 Olaparib
ATM I10fs Olaparib
CHEK2 E87* Olaparib
RAD51C S105* Olaparib
PALB2 K1098* PARP Inhibitor (Pan)
RAD51C C135R Olaparib
RAD51C R312W Olaparib
ATM P2974L Olaparib
CHEK2 Y390C Olaparib
CHEK2 F125S Olaparib
RAD51B R8* Olaparib
CHEK2 D438Y Olaparib
BRIP1 S601* Olaparib
RAD54L K189A Olaparib
CHEK2 V198Ffs*7 Olaparib
CHEK2 H483R Olaparib
BRIP1 R836* Olaparib
RAD54L E297* Olaparib
BRIP1 L860P Olaparib
RAD51C V140G Olaparib
CHEK2 D82_E86del Olaparib
RAD51C V156D Olaparib
ATM P2699L Olaparib
BRIP1 C350F Olaparib
ATM Q2972* Olaparib
ATM R3008C Olaparib
PALB2 L24F PARP Inhibitor (Pan)
ATM I2701Nfs*17 Olaparib
RAD51B loss Olaparib
RAD51C R12W Olaparib
CDK12 S133Kfs*24 Olaparib
CDK12 inact mut Olaparib
ATM T2333Nfs*40 Olaparib
ATM L762Qfs*4 Olaparib
ATM N81Tfs*20 Olaparib
CHEK2 D347N Olaparib
ATM Q284* Olaparib
BARD1 C53W Olaparib
FANCL T224K Olaparib
ATM R250Sfs*3 Olaparib
ATM G2718_K2756del Olaparib
BRIP1 W335L Olaparib
CHEK2 A392P Olaparib
ATM S421* Olaparib
ATM A1742P Olaparib
BARD1 W34R Olaparib
CHEK2 Y139* Olaparib
RAD51C R214C Olaparib
CHEK2 W93R Olaparib
BRIP1 F993A Olaparib
CHEK2 F169L Olaparib
BRIP1 C832Y Olaparib
ATM S824F Olaparib
ATM E2187* Olaparib
ATM R250* Olaparib
FANCL M247V Olaparib
CHEK2 E239K Olaparib
CHEK2 W485G Olaparib
ATM Q2730P Olaparib
FANCL E217K Olaparib
RAD51C T132R Olaparib
ATM I1453fs Olaparib
RAD51C D159A Olaparib
ATM K2756* Olaparib
CHEK2 E161del Olaparib
BARD1 C71Y Olaparib
BRIP1 Q689* Olaparib
ATM V1268* Olaparib
CDK12 L996F Olaparib
ATM Y1961C Olaparib
ATM P2699S Olaparib
BRIP1 Q126* Olaparib
RAD54L R75* Olaparib
ATM V519I Olaparib
CHEK2 T367fs Olaparib
PALB2 S979Vfs*11 PARP Inhibitor (Pan)
ATM L1239fs Olaparib
ATM R3047* Olaparib
RAD51C G153D Olaparib
ATM D1682Y Olaparib
BRIP1 E81* Olaparib
CHEK2 K135Nfs*26 Olaparib
RAD51C inact mut Olaparib
CHEK2 G229S Olaparib
CDK12 K46fs Olaparib
ATM L15fs Olaparib
BARD1 A460T Olaparib
CHEK2 E321* Olaparib
ATM S214fs Olaparib
CHEK2 E273K Olaparib
CHEK2 D162G Olaparib
BRIP1 G690E Olaparib
ATM K2749I Olaparib
RAD51C del Olaparib
ATM L2338P Olaparib
CHEK2 G414E Olaparib
ATM I1441fs Olaparib
PALB2 L35F PARP Inhibitor (Pan)
ATM L2890V Olaparib
CHEK2 I189V Olaparib
BRIP1 N576Kfs*2 Olaparib
BRIP1 R777C Olaparib
RAD51B Y46* Olaparib
BARD1 E287* Olaparib
CHEK2 R180H Olaparib
ATM Q1627* Olaparib
BARD1 D612fs Olaparib
CHEK2 loss Olaparib
BARD1 G681fs Olaparib
ATM H2554D Olaparib
BRIP1 P991A Olaparib
ATM T1743I Olaparib
RAD51D G96C Olaparib
BRIP1 S805* Olaparib
CHEK2 S372F Olaparib
BRIP1 C283S Olaparib
BRIP1 G51* Olaparib
BARD1 S660R Olaparib
BARD1 Q564* Olaparib
BARD1 V767fs Olaparib
ATM V1538fs Olaparib
BRIP1 Y461* Olaparib
BARD1 R406* Olaparib
RAD51C E80* Olaparib
FANCL inact mut Olaparib
RAD54L K189R Olaparib
BARD1 del Olaparib
BARD1 T598I Olaparib
RAD54L E436* Olaparib
ATM I2629fs Olaparib
ATM E390* Olaparib
RAD51D Q41* Olaparib
CDK12 S62fs Olaparib
BRIP1 E626K Olaparib
CDK12 P683Qfs*70 Olaparib
ATM L1956H Olaparib
ATM W524* Olaparib
RAD51C L27P Olaparib
BRIP1 S990A Olaparib
BRIP1 G763C Olaparib
BARD1 S142* Olaparib
ATM N3033* Olaparib
CHEK2 R474C Olaparib
CHEK2 K253* Olaparib
CHEK2 L326P Olaparib
BRIP1 T48Qfs*7 Olaparib
CHEK2 R382* Olaparib
CHEK2 K244R Olaparib
ATM V2716A Olaparib
BRIP1 Q815* Olaparib
ATM K1807E Olaparib
RAD51D V203E Olaparib
RAD51C G114V Olaparib
ATM F2732V Olaparib
CHEK2 K287fs Olaparib
RAD51C Q143R Olaparib
CDK12 R271* Olaparib
BRIP1 S614Y Olaparib
CHEK2 I160T Olaparib
BARD1 L44R Olaparib
BRIP1 loss Olaparib
CDK12 Y901C Olaparib
BRIP1 R173C Olaparib
CDK12 R882L Olaparib
CHEK2 del Olaparib
ATM K468fs Olaparib
CHEK2 D293fs Olaparib
ATM L1449* Olaparib
BRIP1 R762P Olaparib
CHEK2 I160M Olaparib
ATM W2109* Olaparib
PALB2 K862Rfs*9 PARP Inhibitor (Pan)
ATM L2427_R2428del Olaparib
ATM R2547_S2549del Olaparib
CDK12 G879V Olaparib
CHEK2 Y424H Olaparib
ATM inact mut Olaparib
ATM S719* Olaparib
ATM Q1579fs Olaparib
RAD51B L103* Olaparib
ATM S1455Vfs*3 Olaparib
CHEK2 P426R Olaparib
CHEK2 R95* Olaparib
ATM Q1970* Olaparib
BARD1 inact mut Olaparib
ATM E2039* Olaparib
RAD51C T132P Olaparib
BRIP1 R261* Olaparib
BRIP1 R798* Olaparib
ATM Q2522fs Olaparib
RAD51C L265* Olaparib
RAD51D V200* Olaparib
CHEK2 L183F Olaparib
RAD51C T287A Olaparib
ATM R2832C Olaparib
BRIP1 del Olaparib
BRIP1 S189L Olaparib
BARD1 E652fs Olaparib
ATM P960H Olaparib
RAD54L inact mut Olaparib
ATM P1069fs Olaparib
BARD1 G623E Olaparib
RAD51B inact mut Olaparib
RAD51C T102I Olaparib
BARD1 G698D Olaparib
ATM I1849fs Olaparib
ATM M1484Rfs*15 Olaparib
CHEK2 K373E Olaparib
ATM E518fs Olaparib
RAD54L del Olaparib
CHEK2 T410fs Olaparib
RAD51C K131I Olaparib
RAD51D D206A Olaparib
BRIP1 G49R Olaparib
CHEK2 E107_K197del Olaparib
RAD51C R366Q Olaparib
BRIP1 L340R Olaparib
BRIP1 A349P Olaparib
BRIP1 L358P Olaparib
CDK12 K756R Olaparib
CDK12 P58fs Olaparib
CHEK2 T323P Olaparib
ATM Q1171Tfs*8 Olaparib
CHEK2 Q27* Olaparib
FANCL R221W Olaparib
CDK12 loss Olaparib
PALB2 K908fs PARP Inhibitor (Pan)
CDK12 A88fs Olaparib
PALB2 N821Tfs*25 PARP Inhibitor (Pan)
RAD51C F103V Olaparib
RAD54L S49E Olaparib
ATM Q2297* Olaparib
ATM S1403fs Olaparib
ATM K293* Olaparib
BARD1 L465F Olaparib
CHEK2 Y390S Olaparib
ATM S2761Vfs*41 Olaparib
RAD51C G150E Olaparib
BRIP1 V676E Olaparib
CDK12 Y279* Olaparib
BARD1 K209Efs*5 Olaparib
RAD51C Q133E Olaparib
ATM Y54* Olaparib
BRIP1 H396D Olaparib
ATM S333F Olaparib
CHEK2 M381* Olaparib
ATM G2765S Olaparib
ATM K468Efs*18 Olaparib
ATM E2039K Olaparib
ATM E1666* Olaparib
CHEK1 del Olaparib
ATM K2811fs Olaparib
CHEK2 N166S Olaparib
ATM V566Ifs*6 Olaparib
PALB2 inact mut PARP Inhibitor (Pan)
ATM V1941L Olaparib
BARD1 G753D Olaparib
BARD1 K321Nfs*21 Olaparib
CHEK2 H371Y Olaparib
RAD51C G264S Olaparib
RAD51D del Olaparib
ATM R1875* Olaparib
BARD1 C645R Olaparib
BARD1 G451fs Olaparib
CHEK2 C385R Olaparib
CHEK2 H54Pfs*6 Olaparib
BRIP1 K752fs Olaparib
FANCL T367Nfs*13 Olaparib
CHEK2 N290Ifs*15 Olaparib
ATM T2902fs Olaparib
ATM E668* Olaparib
CHEK2 W93Gfs*17 Olaparib
ATM L2572fs Olaparib
BRIP1 C283H Olaparib
RAD51C E146* Olaparib
RAD51C L219S Olaparib
ATM W1058* Olaparib
CHEK2 E275* Olaparib
CHEK2 G306A Olaparib
BRIP1 K703Ifs*3 Olaparib
RAD51C D348V Olaparib
CHEK2 T387S Olaparib
ATM E343* Olaparib
CHEK1 inact mut Olaparib
CHEK2 R117A Olaparib
CHEK2 G370E Olaparib
ATM negative Olaparib
ATM T2666A Olaparib
PALB2 N344Tfs*2 PARP Inhibitor (Pan)
CHEK2 T476K Olaparib
PALB2 W898* PARP Inhibitor (Pan)
BRIP1 S653* Olaparib
ATM L2953Tfs*3 Olaparib
ATM L1874F Olaparib
CHEK2 inact mut Olaparib
CHEK2 G306E Olaparib
CHEK2 F169Lfs*2 Olaparib
BARD1 P530L Olaparib
BARD1 loss Olaparib
CHEK2 A392V Olaparib
CHEK2 Q209* Olaparib
CHEK2 R474H Olaparib
CHEK2 F475Lfs*7 Olaparib
RAD51C G125V Olaparib
RAD51C S163R Olaparib
ATM R3008H Olaparib
CHEK2 A237T Olaparib
BRIP1 L415P Olaparib
CDK12 Y319fs Olaparib
ATM H1380Y Olaparib
CHEK2 L236P Olaparib
CHEK2 R181C Olaparib
BARD1 R565C Olaparib
BRIP1 Q561* Olaparib
ATM G2083* Olaparib
ATM A2067D Olaparib
BRIP1 R279Q Olaparib
ATM Q1906* Olaparib
CHEK2 R474L Olaparib
ATM E2977Rfs*2 Olaparib
RAD51C A155E Olaparib
ATM T2947S Olaparib
ATM W2104* Olaparib
BRIP1 K52R Olaparib
ATM C353fs Olaparib
FANCL D306* Olaparib
CHEK2 D347A Olaparib
CHEK2 C284Y Olaparib
BRIP1 S624* Olaparib
BRIP1 C283R Olaparib
CHEK2 S372Y Olaparib
BARD1 Q164* Olaparib
RAD51C G162Efs*9 Olaparib
CDK12 E1024* Olaparib
PALB2 del PARP Inhibitor (Pan)
BARD1 Q730* Olaparib
CHEK2 T59K Olaparib
RAD51C D108G Olaparib
CHEK2 A392S Olaparib
CHEK2 R318H Olaparib
ATM R2849* Olaparib
CHEK2 S140N Olaparib
ATM S1455R Olaparib
CHEK2 F292fs Olaparib
ATM N2326_K2363del Olaparib
PALB2 E1010* PARP Inhibitor (Pan)
BRIP1 T252R Olaparib
PALB2 H46Y PARP Inhibitor (Pan)
BRIP1 S697P Olaparib
CDK12 S587Ffs*54 Olaparib
CHEK2 Q10fs Olaparib
ATM V2288fs Olaparib
BARD1 N295S Olaparib
CHEK2 E122Dfs*8 Olaparib
RAD51C Q133K Olaparib
FANCL T367fs Olaparib
BRIP1 N541fs Olaparib
CHEK2 H143Y Olaparib
BRIP1 Y408Lfs*14 Olaparib
CHEK2 S428F Olaparib
CDK12 P335fs Olaparib
BARD1 G700Afs*14 Olaparib
CHEK2 G167R Olaparib
CHEK2 G14Afs*47 Olaparib
ATM R1304* Olaparib
PALB2 G808* PARP Inhibitor (Pan)
CDK12 E72fs Olaparib
BARD1 Q564H Olaparib
RAD51C T121R Olaparib
PALB2 Q1023* PARP Inhibitor (Pan)
ATM loss Olaparib
ATM E2272* Olaparib
BRIP1 S772* Olaparib
CDK12 del Olaparib
ATM L2452P Olaparib
ATM V2424G Olaparib
CHEK2 E321K Olaparib
CHEK2 R406Vfs*8 Olaparib
BRIP1 S618* Olaparib
BARD1 S551* Olaparib
ATM W412* Olaparib
CDK12 S343fs Olaparib
ATM I1681V Olaparib
BARD1 K312N Olaparib
BRIP1 E387* Olaparib
CHEK2 T476M Olaparib
ATM H2038Y Olaparib
ATM M2520fs Olaparib
ATM L2738* Olaparib
BRIP1 E501* Olaparib
FANCL I336_C337delinsS Olaparib
ATM R2138Kfs*8 Olaparib
ATM R2691C Olaparib
CHEK2 E394K Olaparib
CHEK2 L174V Olaparib
BRIP1 Q554Hfs*35 Olaparib
CDK12 H111fs Olaparib
ATM D2708N Olaparib
BARD1 P707S Olaparib
ATM V1268fs Olaparib
ATM D1682H Olaparib
BARD1 L480S Olaparib
PALB2 S254Ifs*3 PARP Inhibitor (Pan)
PALB2 Q1056* PARP Inhibitor (Pan)
BRIP1 W448* Olaparib
CDK12 Q944* Olaparib
RAD51C G130A Olaparib
CHEK2 E351K Olaparib
PALB2 L947F PARP Inhibitor (Pan)
RAD54L Q90* Olaparib
PALB2 T494Lfs*67 PARP Inhibitor (Pan)
CDK12 E928fs Olaparib
ATM R2034P Olaparib
ATM Y1229* Olaparib
ATM A2062V Olaparib
BRIP1 Q227* Olaparib
CDK12 E647Kfs*8 Olaparib
ATM Q2800* Olaparib
CDK12 G909R Olaparib
ATM R2912Efs*26 Olaparib
CHEK2 M304T Olaparib
ATM W57* Olaparib
BRIP1 L347P Olaparib
CDK12 L122* Olaparib
BRIP1 E795* Olaparib
ATM A302fs Olaparib
ATM S1993Rfs*23 Olaparib
ATM N1650S Olaparib
CDK12 D877N Olaparib
ATM R1882* Olaparib
ATM R2849P Olaparib
PALB2 Q790* PARP Inhibitor (Pan)
ATM R805* Olaparib
ATM S2394L Olaparib
CHEK2 E64K Olaparib
ATM T2333fs Olaparib
CDK12 R204fs Olaparib
RAD51B del Olaparib
BRIP1 Y147* Olaparib
CHEK2 C420T Olaparib
CDK12 Q602* Olaparib
RAD51C A279P Olaparib
BARD1 C83R Olaparib
ATM Q628Pfs*7 Olaparib
CHEK2 L216* Olaparib
RAD51D G112A Olaparib
RAD51C D159Y Olaparib
CHEK2 D409N Olaparib
CHEK2 A230P Olaparib
RAD51D inact mut Olaparib
BRIP1 V341D Olaparib
CHEK2 S422Vfs*15 Olaparib
BRIP1 Q25* Olaparib
ATM S131* Olaparib
ATM S978fs Olaparib
ATM P292L Olaparib
BRIP1 G49* Olaparib
ATM V2119fs Olaparib
ATM E473* Olaparib
ATM Q1636Rfs*10 Olaparib
PALB2 R414* PARP Inhibitor (Pan)
CHEK2 F202fs Olaparib
BRIP1 R865W Olaparib
ATM R2034* Olaparib
ATM R2598* Olaparib
BRIP1 L392* Olaparib
ATM R1466* Olaparib
CHEK2 S357F Olaparib
ATM Q2277* Olaparib
CHEK2 K224E Olaparib
CHEK2 I157T Olaparib
PALB2 loss PARP Inhibitor (Pan)
RAD51D S207L Olaparib
ATM dec exp Olaparib
ATM C2488Y Olaparib
ATM P604S Olaparib
RAD51D loss Olaparib
ATM S2855_V2856delinsRI Olaparib
ATM S751* Olaparib
ATM L1465P Olaparib
BRIP1 P47A Olaparib
BRIP1 E726* Olaparib
ATM F2827C Olaparib
BRIP1 S913fs Olaparib
RAD51D K91fs Olaparib
ATM Y2371* Olaparib
ATM E277* Olaparib
ATM R337S Olaparib
CHEK2 R148G Olaparib
BRIP1 R439* Olaparib
RAD54L F82S Olaparib
ATM T1200Lfs*7 Olaparib
ATM Y1442* Olaparib
CDK12 S785fs Olaparib
PALB2 K346Tfs*13 PARP Inhibitor (Pan)
ATM del Olaparib
ATM E2304Gfs*69 Olaparib
ATM C540* Olaparib
CHEK2 C108R Olaparib
ATM S2592C Olaparib
BRIP1 R831K Olaparib
CHEK2 K249R Olaparib
BRIP1 Q685* Olaparib
BRIP1 I983fs Olaparib
RAD54L loss Olaparib
BRIP1 G224* Olaparib
CHEK2 T367Mfs*15 Olaparib
ATM I1581Nfs*5 Olaparib
RAD54L L381Cfs*8 Olaparib
CHEK2 R117G Olaparib
BRIP1 T997fs Olaparib
BRIP1 S697F Olaparib
CDK12 T212fs Olaparib
BRIP1 Q645* Olaparib
RAD51C C135Y Olaparib
RAD51C L226P Olaparib
CHEK2 N185fs Olaparib
CHEK1 R379* Olaparib
ATM K1410* Olaparib
ATM F1025L Olaparib
BRIP1 F366S Olaparib
BRIP1 I504fs Olaparib
CHEK2 A247D Olaparib
CHEK2 Q34Vfs*42 Olaparib
CHEK2 T366fs Olaparib
FANCL Q18* Olaparib
BARD1 V154fs Olaparib
CDK12 K975E Olaparib
CHEK2 E149Ifs*6 Olaparib
RAD54L P85A Olaparib
CHEK2 P85R Olaparib
RAD51C loss Olaparib
RAD51D G107V Olaparib
BRIP1 K998Efs*60 Olaparib
CHEK2 S412R Olaparib
ATM L804fs Olaparib
ATM R2993* Olaparib
ATM R1730* Olaparib
ATM I1294Nfs*8 Olaparib
CHEK2 L183S Olaparib
CDK12 F89Sfs*3 Olaparib
RAD54L Y309* Olaparib
ATM S2017fs Olaparib
ATM S214Pfs*16 Olaparib
ATM S2812Vfs*3 Olaparib
BRIP1 inact mut Olaparib
ATM R1618* Olaparib
BRIP1 R848H Olaparib
CHEK2 I160R Olaparib
ATM S2407* Olaparib
CHEK2 H143R Olaparib
ATM Y2019C Olaparib
ATM A2602fs Olaparib
ATM R2506_N2543del Olaparib
ATM V278fs Olaparib
ATM L2427P Olaparib
ATM Q2397* Olaparib
BRIP1 P785L Olaparib
ATM R1898* Olaparib
ATM E522* Olaparib
PALB2 R1086Efs*9 PARP Inhibitor (Pan)
BRIP1 R581* Olaparib
RAD51C G302V Olaparib
CHEK2 N352D Olaparib
CHEK2 L309P Olaparib
RAD51C V140E Olaparib
ATM S1993fs Olaparib
BRIP1 G690R Olaparib
ATM N765Kfs*12 Olaparib
ATM G2867R Olaparib
CDK12 W719* Olaparib
RAD51D E37* Olaparib
ATM W2300* Olaparib
RAD51C R258H Olaparib
ATM A59S Olaparib
CHEK2 G386R Olaparib
ATM E1978* Olaparib
CHEK2 R145W Olaparib
RAD51C R193* Olaparib
RAD51C L138F Olaparib
ATM F2571Yfs*4 Olaparib
RAD51C R237P Olaparib
ATM E1072* Olaparib
CHEK2 D265_H282del Olaparib
BRIP1 D393V 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
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...
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
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...
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
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
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
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
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
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...
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
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 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), and median overall survival (18.5 vs 15.1 mo, HR 0.64, p=0.02) compared to control in metastatic castration-resistant prostate cancer patients harboring deleterious or suspected deleterious BRCA or ATM mutations, HR for progression or death was 1.04 in ATM-mutant patients (PMID: 32343890; NCT02987543). detail... 32343890 detail...