PURPOSE To investigate quality-adjusted progression-free survival (QA-PFS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) in a post hoc exploratory analysis of the phase III ARIEL3 study of rucaparib maintenance treatment versus placebo. PATIENTS AND METHODS Patients with platinum-sensitive, recurrent ovarian carcinoma were randomly assigned to rucaparib (600 mg twice per day) or placebo. QA-PFS was calculated as progression-free survival function 3 the 3-level version of the EQ-5D questionnaire (EQ-5D-3L) index score function. Q-TWiST analyses were performed defining TOX as the mean duration in which a patient experienced grade $ 3 treatment-emergent adverse events (TEAEs) or the mean duration in which a patient experienced grade $ 2 TEAEs of nausea, vomiting, fatigue, and asthenia. Q-TWiST was calculated as mTOX 3 TOX 1 TWiST, with mTOX calculated using EQ-5D-3L data. RESULTS The visit cutoff was Apr 15, 2017. Mean QA-PFS was significantly longer with rucaparib versus placebo in the intent-to-treat (ITT) population (375 randomly assigned to rucaparib v 189 randomly assigned to placebo; difference, 6.28 months [95% CI, 4.85 to 7.47 months]); BRCA-mutant cohort (130 rucaparib v 66 placebo; 9.37 months [95% CI, 6.65 to 11.85 months]); homologous recombination deficient (HRD) cohort (236 rucaparib v 118 placebo; 7.93 months [95% CI, 5.93 to 9.53 months]); and BRCA wild-type/loss of heterozygosity (LOH) low patient subgroup (107 rucaparib v 54 placebo; 2.71 months [95% CI, 0.31 to 4.44 months]). With TOX defined using grade $ 3 TEAEs, the difference in mean Q-TWiST (rucaparib v placebo) was 6.88 months (95% CI, 5.71 to 8.23 months), 9.73 months (95% CI, 7.10 to 11.94 months), 8.11 months (95% CI, 6.36 to 9.49 months), and 3.35 months (95% CI, 1.66 to 5.40 months) in the ITT population, BRCA-mutant cohort, HRD cohort, and BRCA wild-type/LOH low patient subgroup, respectively. Q-TWiST with TOX defined using select grade $ 2 TEAEs also consistently favored rucaparib. CONCLUSION The significant differences in QA-PFS and Q-TWiST confirm the benefit of rucaparib versus placebo in all predefined cohorts.

Oza, A. M., Lorusso, D., Aghajanian, C., Oaknin, A., Dean, A., Colombo, N., Weberpals, J. I., Clamp, A. R., Scambia, G., Leary, A., Holloway, R. W., Gancedo, M. A., Fong, P. C., Goh, J. C., O'Malley, D. M., Armstrong, D. K., Banerjee, S., Garcia-Donas, J., Swisher, E. M., Cella, D., Meunier, J., Goble, S., Cameron, T., Maloney, L., Mork, A. -., Bedel, J., Ledermann, J. A., Coleman, R. L., Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients with Recurrent Ovarian Carcinoma, <<JOURNAL OF CLINICAL ONCOLOGY>>, 2020; 38 (30): 3494-3505. [doi:10.1200/JCO.19.03107] [http://hdl.handle.net/10807/167348]

Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients with Recurrent Ovarian Carcinoma

Lorusso, Domenica;Scambia, Giovanni;
2020

Abstract

PURPOSE To investigate quality-adjusted progression-free survival (QA-PFS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) in a post hoc exploratory analysis of the phase III ARIEL3 study of rucaparib maintenance treatment versus placebo. PATIENTS AND METHODS Patients with platinum-sensitive, recurrent ovarian carcinoma were randomly assigned to rucaparib (600 mg twice per day) or placebo. QA-PFS was calculated as progression-free survival function 3 the 3-level version of the EQ-5D questionnaire (EQ-5D-3L) index score function. Q-TWiST analyses were performed defining TOX as the mean duration in which a patient experienced grade $ 3 treatment-emergent adverse events (TEAEs) or the mean duration in which a patient experienced grade $ 2 TEAEs of nausea, vomiting, fatigue, and asthenia. Q-TWiST was calculated as mTOX 3 TOX 1 TWiST, with mTOX calculated using EQ-5D-3L data. RESULTS The visit cutoff was Apr 15, 2017. Mean QA-PFS was significantly longer with rucaparib versus placebo in the intent-to-treat (ITT) population (375 randomly assigned to rucaparib v 189 randomly assigned to placebo; difference, 6.28 months [95% CI, 4.85 to 7.47 months]); BRCA-mutant cohort (130 rucaparib v 66 placebo; 9.37 months [95% CI, 6.65 to 11.85 months]); homologous recombination deficient (HRD) cohort (236 rucaparib v 118 placebo; 7.93 months [95% CI, 5.93 to 9.53 months]); and BRCA wild-type/loss of heterozygosity (LOH) low patient subgroup (107 rucaparib v 54 placebo; 2.71 months [95% CI, 0.31 to 4.44 months]). With TOX defined using grade $ 3 TEAEs, the difference in mean Q-TWiST (rucaparib v placebo) was 6.88 months (95% CI, 5.71 to 8.23 months), 9.73 months (95% CI, 7.10 to 11.94 months), 8.11 months (95% CI, 6.36 to 9.49 months), and 3.35 months (95% CI, 1.66 to 5.40 months) in the ITT population, BRCA-mutant cohort, HRD cohort, and BRCA wild-type/LOH low patient subgroup, respectively. Q-TWiST with TOX defined using select grade $ 2 TEAEs also consistently favored rucaparib. CONCLUSION The significant differences in QA-PFS and Q-TWiST confirm the benefit of rucaparib versus placebo in all predefined cohorts.
2020
Inglese
Oza, A. M., Lorusso, D., Aghajanian, C., Oaknin, A., Dean, A., Colombo, N., Weberpals, J. I., Clamp, A. R., Scambia, G., Leary, A., Holloway, R. W., Gancedo, M. A., Fong, P. C., Goh, J. C., O'Malley, D. M., Armstrong, D. K., Banerjee, S., Garcia-Donas, J., Swisher, E. M., Cella, D., Meunier, J., Goble, S., Cameron, T., Maloney, L., Mork, A. -., Bedel, J., Ledermann, J. A., Coleman, R. L., Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients with Recurrent Ovarian Carcinoma, <<JOURNAL OF CLINICAL ONCOLOGY>>, 2020; 38 (30): 3494-3505. [doi:10.1200/JCO.19.03107] [http://hdl.handle.net/10807/167348]
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