Article Figures & Data
Tables
- Table 1.
Patient, tumor, and treatment characteristics
Characteristics Values Total no. of patients 89 Age (y), median (range) 51 (31–77) Stage at diagnosis—no. (%) 1 5 (6) 2 7 (8) 3 63 (71) 4 8 (9) Not known 6 (7) Histology grade—no. (%) 2 13 (15) 3 66 (74) Not known 10 (11) Histology—no. (%) Serous papillary 67 (75) Endometrioid 7 (8) Adenocarcinoma not otherwise specified 15 (17) Prior no. of lines of systemic chemotherapy (excluding olaparib)—no. (%) 1 13 (15) 2 30 (34) 3 23 (26) ≥4 21 (24) Not known 2 (2) BRCA mutation status—no. (%) BRCA1 66 (74) BRCA2 23 (26) Optimally debulked—no. (%) Yes 48 (54) No 23 (26) Not known 18 (20) Previous breast cancer—no. (%) Yes 29 (33) Chemotherapy for breast cancer 11 (38) No 60 (67) Sensitivity to last pre-PARPi platinum chemotherapy—no. (%) Sensitive (TFI >12 m) 15 (17) Partially sensitive (TFI >6 and ≤12 m) 38 (43) Resistant (TFI <6 m) 36 (40) Overall response rate to olaparib—no. of responses/no. evaluable (%) RECIST 34/86 (40) RECIST and/or CA125 41/87 (47) - Table 2.
Types and efficacies of chemotherapies used in the post-olaparib first-line setting
RECIST RECIST and/or GCIG Regimens Evaluable Responses (%) Evaluable Responses (%) Platinum-based chemotherapies 48 19 (40) 53 26 (49) Platinum single-agent 6 3 (50) 6 3 (50) Platinum-taxane 19 8 (42) 22 14 (64) Platinum-PLD 10 4 (40) 11 5 (45) Platinum-others 13 4 (31) 14 4 (29) Taxane single-agent 10 4 (40) 10 5 (50) PLD single-agent 5 0 (0) 10 3 (30) Others 4 1 (25) 5 1 (20) Total 67 24 (36) 78 35 (45) - Table 3.
Breakdown of objective responses to different chemotherapeutic regimens used in the post-PARPi setting according to pre-PARPi platinum sensitivity
Response by RECIST and/or GCIG criteria (events/evaluable; %) Chemotherapeutic regimen used Platinum-resistant Platinum-partially sensitive Platinum-sensitive Platinum-based chemotherapies 5/14 (36) 16/26 (62) 5/13 (38) Platinum single-agent 1/3 (33) 1/2 (50) 1/1 (100) Platinum-taxane 3/5 (60) 9/10 (90) 2/7 (29) Platinum-PLD 1/4 (25) 3/5 (60) 1/2 (50) Platinum-others 0/2 (0) 3/9 (33) 1/3 (33) Taxane single-agent 3/8 (38) 2/2 (100) 0/0 (0) PLD single-agent 2/6 (33) 1/3 (33) 0/1 (0) Others 1/2 (50) 0/3 (0) 0/0 (0) Total 11/30 (37) 19/34 (56) 5/14 (36) - Table 4.
Table summarizing the association of baseline factors with OS in patients treated with platinum-based chemotherapy in the post-olaparib setting
Univariate Multivariate Variables HR P HR P Age (y) 0.981 (0.948–1.015) 0.267 - - Grade (3 vs. 2) 1.066 (0.325–3.493) 0.916 - - Stage at diagnosis (III or IV vs. I or II) 1.072 (0.442–2.599) 0.877 - - Serous histology 0.834 (0.293–2.380) 0.735 - - Optimally debulked (<1 cm) 0.598 (0.291–1.229) 0.162 - - BRCA2 vs. BRCA1 0.970 (0.461–2.042) 0.936 - - Previous breast cancer 0.661 (0.341–1.281) 0.220 - - Residual disease after first-line treatment 1.665 (0.773–3.588) 0.193 - - Olaparib RECIST and/or GCIG response 0.031 0.056 SD vs. PD 0.299 (0.103–0.868) 0.026 0.301 (0.104–0.875) 0.027 PR/CR vs. PD 0.257 (0.093–0.709) 0.009 0.298 (0.106–0.838) 0.022 Last pre-PARPi platinum sensitivity 0.332 Partial sensitive vs. resistant 0.902 (0.448–1.815) 0.773 - - Sensitive vs. resistant 0.522 (0.214–1.276) 0.154 PTP interval (mo) 0.960 (0.928–0.993) 0.018 0.962 (0.928–0.997) 0.036 - Table 5.
Associations between objective response to first-line post-olaparib platinum-based chemotherapy and (i) olaparib response, (ii) pre-olaparib platinum sensitivity (measured by TFI), and (iii) interval between last pre-olaparib and first post-olaparib platinum-based chemotherapies (PTP interval)
Post-olaparib platinum chemotherapy response by RECIST and/or GCIG criteria SD vs. PD PR/CR vs. PD P OR (95% CI) P OR (95% CI) Olaparib response by RECIST and/or GCIG SD vs. PD 0.105 14 (0.58–338.78) 0.184 7.0 (0.40–123.35) PR/CR vs. PD 0.341 3.6 (0.26–50.33) 0.275 3.4 (0.38—30.66) TFI after last pre-PARPi platinum (months) 0.874 1.008 (0.915–1.110) 0.921 1.005 (0.916–1.102) PTP interval (months) 0.061 1.117 (0.995–1.254) 0.045 1.124 (1.003–1.264) - Table 6.
Results of massively parallel sequencing of tumors obtained from the six patients in this study.
BRCA1 mutation reads (%) BRCA2 mutation reads (%) TP53 mutation reads (%) Patient Time of tumor biopsy Biopsy site BRCA1 mutation (rs number) Wild-type alleles Mutant alleles BRCA2 mutation (rs number) Wild-type alleles Mutant alleles TP53 mutation Wild-type alleles Mutant alleles 1 Diagnosis Right ovary c.3005delA/p.N1002fs (80357846) 257 (58) 183 (42) c.5946delT p.2003 (80359550) 17 (89) 2 (11) c.949C>T/p.Q317* 169 (76) 52 (24) Diagnosis Left ovary c.3005delA/p.N1002fs (80357846) 79 (24) 244 (76) – – – c.949C>T/p.Q317* 179 (79) 48 (21) Diagnosis LN c.3005delA/p.N1002fs (80357846) 112 (21) 426 (79) – – – c.949C>T/p.Q317* 178 (77) 52 (23) Post-PARPi LN 1 c.3005delA/p.N1002fs (80357846) 102 (18) 453 (82) – – – c.949C>T/p.Q317* 164 (71) 66 (29) Post-PARPi LN 2 c.3005delA/p.N1002fs (80357846) 88 (17) 435 (83) – – – c.949C>T/p.Q317* 160 (73) 59 (27) 2 Diagnosis Right ovary c.3760_3761insT/p.K1254fs (80357986) 87 (42) 120 (58) – – – c.659A>G/p.Y220C 15 (42) 21 (58) Post-PARPi Pelvic sidewall tumor c.3760_3761insT/p.K1254fs (80357986) 130 (51) 126 (49) c.659A>G/p.Y220C 1 (6) 16 (94) 3 Diagnosis Left ovary c.66_67delAG/p.E23fs (80357713) 28 (17) 132 (83) — — — – – – Post-PARPi Peritoneal tumor c.66_67delAG/p.E23fs (80357713) 24 (27) 66 (73) 4 Post first-line Vaginal vault lesion c.3450_3453delCAAG/p.Q1111fs (80357903) 50 (12) 382 (88) — — — – – – Post-PARPi Para-aortic LN c.3450_3453delCAAG/p.Q1111fs (80357903) 74 (20) 298 (80) 5 Post-PARPi Ascites – — — c.8975_9100del/p.Pro2992_Gln3034 (80359736) 167 (61) 104 (38) c.794A>G/p.L265P 60 (79) 16 (21) 6 Post-PARPi Ascites c.1961_1962insA/p.K654fs (80357853) 311 (57) 232 (43) — — — c.489insTGCTTG/pS166* 243 (98) 5 (2) Abbreviation: LN, lymph node.
Additional Files
Supplementary Data
Files in this Data Supplement:
- Supplementary Table 1 - Supplementary Table 1 - PDF file 57K, Supplementary Table 1. Details of platinum sensitivity and best response to olaparib and post-PARPi chemotherapy of the six patients whose tumor samples were analyzed by massively parallel sequencing. (NE: not evaluable)
October 2013
Volume 19, Issue 19
Volume 19, Issue 19
Efficacy of Chemotherapy in BRCA1/2 Mutation Carrier Ovarian Cancer in the Setting of PARP Inhibitor Resistance: A Multi-Institutional Study
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