Phase i study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours

G. Del Conte, C. Sessa, R. Von Moos, L. Viganò, T. Digena, A. Locatelli, E. Gallerani, A. Fasolo, A. Tessari, R. Cathomas, L. Gianni

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Background:Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221).Methods:Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m-2, day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)).Results:Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinum-sensitive, 11 had a gBRCA mutation.Conclusions:Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m-2) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.

Original languageEnglish
Pages (from-to)651-659
Number of pages9
JournalBritish Journal of Cancer
Volume111
Issue number4
DOIs
Publication statusPublished - Aug 12 2014

Fingerprint

Neoplasms
Ovarian Neoplasms
Pneumonia
Pharmacokinetics
Stomatitis
Maximum Tolerated Dose
liposomal doxorubicin
olaparib
Platinum
Capsules
Breast
1-dodecylpyridoxal
Breast Neoplasms
Safety
Mutation

Keywords

  • advanced solid tumours
  • liposomal doxorubicin
  • olaparib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase i study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours. / Del Conte, G.; Sessa, C.; Von Moos, R.; Viganò, L.; Digena, T.; Locatelli, A.; Gallerani, E.; Fasolo, A.; Tessari, A.; Cathomas, R.; Gianni, L.

In: British Journal of Cancer, Vol. 111, No. 4, 12.08.2014, p. 651-659.

Research output: Contribution to journalArticle

Del Conte, G, Sessa, C, Von Moos, R, Viganò, L, Digena, T, Locatelli, A, Gallerani, E, Fasolo, A, Tessari, A, Cathomas, R & Gianni, L 2014, 'Phase i study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours', British Journal of Cancer, vol. 111, no. 4, pp. 651-659. https://doi.org/10.1038/bjc.2014.345
Del Conte, G. ; Sessa, C. ; Von Moos, R. ; Viganò, L. ; Digena, T. ; Locatelli, A. ; Gallerani, E. ; Fasolo, A. ; Tessari, A. ; Cathomas, R. ; Gianni, L. / Phase i study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours. In: British Journal of Cancer. 2014 ; Vol. 111, No. 4. pp. 651-659.
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T1 - Phase i study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours

AU - Del Conte, G.

AU - Sessa, C.

AU - Von Moos, R.

AU - Viganò, L.

AU - Digena, T.

AU - Locatelli, A.

AU - Gallerani, E.

AU - Fasolo, A.

AU - Tessari, A.

AU - Cathomas, R.

AU - Gianni, L.

PY - 2014/8/12

Y1 - 2014/8/12

N2 - Background:Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221).Methods:Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m-2, day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)).Results:Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinum-sensitive, 11 had a gBRCA mutation.Conclusions:Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m-2) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.

AB - Background:Olaparib, an oral PARP inhibitor, has shown antitumour activity as monotherapy in patients with germline BRCA1/2 (gBRCA)-mutated breast and ovarian cancer. This study evaluated olaparib capsules in combination with liposomal doxorubicin (PLD) in patients with advanced solid tumours (NCT00819221).Methods:Patients received 28-day cycles of olaparib, continuously (days 1-28) or intermittently (days 1-7), plus PLD (40 mg m-2, day 1); seven olaparib dose cohorts (50-400 mg bid) were explored to determine the recommended dose. Assessments included safety, pharmacokinetics, pharmacodynamics and preliminary efficacy (objective response rate (ORR)).Results:Of 44 patients treated (ovarian, n=28; breast, n=13; other/unknown, n=3), two experienced dose-limiting toxicities (grade 3 stomatitis and fatal pneumonia/pneumonitis (200 mg per 28-day cycle); grade 4 thrombocytopenia (400 mg per 7-day cycle)). The maximum tolerated dose was not reached using continuous olaparib 400 mg bid plus PLD. Grade ≥3 and serious AEs were reported for 27 (61%) and 12 (27%) patients, respectively. No major pharmacokinetic interference was observed between olaparib and PLD. The ORR was 33% (n=14 out of 42; complete response, n=3). A total of 13 responders had ovarian cancer: 10 were platinum-sensitive, 11 had a gBRCA mutation.Conclusions:Continuous/intermittent olaparib (up to 400 mg bid) combined with PLD (40 mg m-2) was generally tolerated and showed evidence of antitumour activity in ovarian cancer.

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