. 2018 Sep 28;9:3970. doi: 10.1038/s41467-018-05564-z

Table 1.

Responses observed in 12 HGSOC PDX to cisplatin and rucaparib treatment in vivo

PDX #	Baseline tumor	Patient response to platinum agents/PARP inhibitors^a	HR gene defect	TTH vehicle	Cisplatin response in PDX				Rucaparib (300 mg kg⁻¹) response in PDX				Explored mechanisms of resistance to rucaparib in vivo
PDX #	Baseline tumor	Patient response to platinum agents/PARP inhibitors^a	HR gene defect	TTH vehicle	Response	Median TTH (days)	Average TTP (days)	p-value	Response	Median TTH (days)	Average TTP (days)	p-value	Explored mechanisms of resistance to rucaparib in vivo
#54	Chemo-naive	Platinum sensitive^a PARPi unknown	BRCA1:c.5095C>T	32	Resistant SD	78	50	0.010	Refractory PD	36	8	0.900	No secondary mutations; BRCA1 structural reversion predicted
#56	Chemo-naive	Platinum sensitive^a PARPi 2 ^nd line single agent CR	BRCA1:c.894_895delTG	15	Sensitive CR	>120	113	<0.001	Response SD	95	53	<0.001	No secondary mutations
#13	Chemo-naive	Platinum resistant^a No PARPi	BRCA2:c.5517_5518delA	43	Resistant PR	>120	99	<0.001	Minimal response SD	81	32	0.010	No secondary mutations
#19	Chemo-naive	Platinum sensitive^a PARPi unknown	BRCA2:c.2323_2323delT	22	Sensitive CR	>120	>120	<0.001	Response CR	>120	>120	<0.001	No secondary mutations
#11	Chemo-naive	Platinum sensitive^a PARPi 4 ^th line single agent PR for 11 months	BRCA1 methylation homozygous	46	Sensitive CR	>120	>120	<0.001	Not assessed	–	–	–	No loss of methylation
#62	Chemo-naive	Platinum sensitive^a No PARPi	BRCA1 methylation homozygous	18	Resistant/Refractory SD	60	46	<0.001	Response SD	71	50	<0.001	No loss of methylation
#48	Pre-treated	Platinum resistant PARPi 3rd line single agent refractory	BRCA1 methylation heterozygous	36	Resistant SD	>120	43	<0.001	Refractory PD	67	8	0.095	No further loss of methylation
#169	Pre-treated	Platinum refractory No PARPi	BRCA1 methylation heterozygous	29	Refractory PD	67	8	0.077	Refractory^b PD	36	8	0.924	No further loss of methylation
#201	Chemo-naive	Platinum sensitive No PARPi	HR-DNA repair gene wild type	25	Resistant PR	99	57	<0.001	Refractory PD	46	8	<0.001^c	–
#27	Chemo-naive	Platinum sensitive^a,d No PARPi	HR-DNA repair gene wild type	22	Resistant PR	109	57	0.001	Refractory PD	36	8	0.887	–
#29	Chemo-naive	Platinum refractory^a No PARPi	HR-DNA repair gene wild type	25	Refractory PD	32	8	0.128	Refractory PD	32	8	0.306	–
#80	Chemo-naive	Platinum sensitive No PARPi	HR-DNA repair gene wild type	53	Sensitive CR	>120	>120	0.021	Refractory PD	64	15	0.021^c	–

PDX were derived from the chemo-naive baseline patient HGSOC samples apart from PDX #48, derived from a patient who had undergone three prior chemotherapeutic regimens, and PDX #169, generated from ascites fluid (the only PDX in this study not to be derived from solid tumor) from a young woman whose HGSOC progressed 1 month after completing first-line therapy and was refractory to second-line platinum treatment. Bold—patient PARPi response

TTH time to harvest, TTP time to progression, SD stable disease, CR complete response, PR partial response, PD progressive disease

^aAs previously reported³⁴

^bRucaparib 450 mg kg⁻¹

^cNo tumor regressions or stabilization of disease was achieved despite significant p-value

^dClinical trial involving standard chemotherapy with placebo/novel agent, followed by maintenance therapy with placebo/novel agent