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Durvalumab, a PD-L1 inhibitor, and Olaparib, a PARP inhibitor, in recurrent ovarian cancer


The PARP inhibitor, Olaparib ( Lynparza ) has shown clinical activity in subsets of recurrent ovarian cancer patients.
Researchers have hypothesized increased DNA damage by Olaparib may complement anti-tumor activity of immune checkpoint blockade with Durvalumab in recurrent ovarian cancer.
The safety data and recommended phase 2 dose ( RP2D ) of Durvalumab plus Olaparib were previously reported.

Eligible patients with PS 0-1, good end organ function and biopsiable disease received the recommended phase 2 dose ( Olaparib 300 mg orally twice daily and Durvalumab 1500mg IV on day 1 of each 28-day cycle ).

The primary objective was to estimate clinical activity using RECIST v1.1 response rate ( RR ) and a 2-stage design targeting 35 evaluable patients.
Safety was assessed by CTCAEv4.0.

Tissue and blood samples were collected pre-treatment and on therapy ( cycle 1 day 15 and cycle 3 day 1 ).

35 patients received at least 1 cycle of treatment ( median age 67 year-old [ range 40-85 ], 6 germline BRCA mutation carriers [ gBRCAm; 17% ] / 29 BRCA wild type [ BRCAwt; 83% ] ).

30 patients ( 86% ) had Platinum-resistant recurrent disease.

Median number of prior therapy regimens was 3.5 ( 1-16 ).

Among 34 evaluable patients ( 6 gBRCAm/28 BRCAwt ), 5 PRs were observed ( 15% RR, median 11months [ 6.5-23 ] ): 2 patients with gBRCAm ( Platinum-resistant [ 8.5months ] and -sensitive disease [ 11+months ] ) and 3 patients with BRCAwt ( Platinum-resistant [ 2; 23 and 14+months ] and -sensitive disease [ 6.5months ] ).

13 patients ( 3 gBRCAm/10 BRCAwt ) had stable disease greater than or equal to 4 months ( median 6.5 months [ 4-12.5 ] ), yielding 53% disease control rate ( partial response plus stable disease greater than or equal to 4 months ).

Grade 3/4 adverse events include anemia ( 26% ) and lymphopenia ( 14% ).

3 patients required Olaparib dose reduction due to grade 3 anemia ( 1 ), grade 3 atrial fibrillation ( 1 ) and recurrent grade 2 nausea refractory to supportive care ( 1 ).

In conclusion, the results suggested Durvalumab plus Olaparib was well-tolerated and had clinical activity in a subgroup of heavily pretreated BRCAwt ovarian cancer patients.
Biomarker evaluation is ongoing to further characterize the subset of patients who had benefit from Durvalumab plus Olaparib. ( Xagena )

Source: European Society of Medical Oncology - ESMO Congress, 2018

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