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In this edition of “Applying research to practice,” I highlight a study suggesting olaparib is helpful in patients BRCA mutations experiencing multiple relapses of ovarian cancer.
SOLO3 was the first phase 3 trial comparing the oral PARP inhibitor olaparib (OLA; 300 mg twice daily) with physician’s choice of intravenous single-agent chemotherapy (TPC) in relapsed high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer (J Clin Oncol. 2020 Feb 19. doi: 10.1200/JCO.19.02745).
The trial involved 266 BRCA-mutated patients who had received two (approximately 50%) or more lines of platinum-based TPC. All patients were required to be completely platinum sensitive (progression beyond 12 months from last platinum exposure) or partially platinum sensitive (progression within 6-12 months).
Women were randomized to receive either OLA or nonplatinum TPC (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). After an amendment to the study in 2017, the primary endpoint was objective response rate, determined by blinded independent central review, with a variety of secondary endpoints.
Among 223 patients with measurable disease, the objective response rate was 72.2% with OLA and 51.4% with TPC (odds ratio, 2.53; P = .002). Across all patients, the median progression-free survival was significantly better with OLA (13.4 months) than with TPC (9.2 months; P = .013). Overall survival data were immature.
The superiority of OLA for the primary endpoint was maintained in multiple subgroups of patients, including those who had received only two prior lines of therapy (OR, 3.44) and those who had three or more prior lines (OR, 2.21). Time to first subsequent therapy (HR, 0.48) and time to treatment discontinuation or death (HR, 0.17) were significantly longer for OLA than for TPC.
Adverse events were consistent with the established safety profiles of OLA and chemotherapy. The most common grade 3 or higher adverse events were anemia (21.3%) with OLA and neutropenia (15.8%) and hand-foot syndrome (11.8%) with TPC.
However, median treatment durations were substantially and consistently longer for OLA than for TPC, and there were fewer treatment discontinuations because of toxicity for OLA than for TPC. At the time of data cutoff, 43 patients in the OLA group and 1 patient in the TPC cohort remained on treatment.
How these results influence practice
The results of the SOLO3 trial are clear: Treatment with OLA is a reasonable alternative to nonplatinum-containing chemotherapy for women with BRCA mutations and platinum-sensitive ovarian cancer. OLA is a “chemotherapy-free” option for these patients in the second- and later-line settings.
Less clear are the following:
- How many patients with BRCA mutations will not have already received a PARP inhibitor in the frontline maintenance setting in the future? SOLO3 required modification in the accrual target and endpoint because of challenges in patient recruitment from the entry of PARP inhibitors into routine clinical practice.
- Would OLA be superior to a carboplatin doublet rather than a nonplatinum single agent in patients with two prior relapses of platinum-sensitive ovarian cancer? Standard practice would be for patients in the second-line setting to receive a platinum doublet.
- Is extending the platinum-free interval a worthwhile objective, or would some patients prefer a finite interval of a platinum doublet over an indefinite period of treatment with OLA?
All phase 3 clinical trials have limitations since they require years to complete and the applicability of the results are challenged by intercurrent advances in treatment options and diagnostic tests.
However, overall, the results of SOLO3 are impressive and should influence clinical practice for the subset of relapsed ovarian cancer patients who would have qualified to participate in it. OLA represents an important treatment advance for a group of patients who are trying to string together remission after remission, with limited negative impact on quality of life.
Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
In this edition of “Applying research to practice,” I highlight a study suggesting olaparib is helpful in patients BRCA mutations experiencing multiple relapses of ovarian cancer.
SOLO3 was the first phase 3 trial comparing the oral PARP inhibitor olaparib (OLA; 300 mg twice daily) with physician’s choice of intravenous single-agent chemotherapy (TPC) in relapsed high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer (J Clin Oncol. 2020 Feb 19. doi: 10.1200/JCO.19.02745).
The trial involved 266 BRCA-mutated patients who had received two (approximately 50%) or more lines of platinum-based TPC. All patients were required to be completely platinum sensitive (progression beyond 12 months from last platinum exposure) or partially platinum sensitive (progression within 6-12 months).
Women were randomized to receive either OLA or nonplatinum TPC (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). After an amendment to the study in 2017, the primary endpoint was objective response rate, determined by blinded independent central review, with a variety of secondary endpoints.
Among 223 patients with measurable disease, the objective response rate was 72.2% with OLA and 51.4% with TPC (odds ratio, 2.53; P = .002). Across all patients, the median progression-free survival was significantly better with OLA (13.4 months) than with TPC (9.2 months; P = .013). Overall survival data were immature.
The superiority of OLA for the primary endpoint was maintained in multiple subgroups of patients, including those who had received only two prior lines of therapy (OR, 3.44) and those who had three or more prior lines (OR, 2.21). Time to first subsequent therapy (HR, 0.48) and time to treatment discontinuation or death (HR, 0.17) were significantly longer for OLA than for TPC.
Adverse events were consistent with the established safety profiles of OLA and chemotherapy. The most common grade 3 or higher adverse events were anemia (21.3%) with OLA and neutropenia (15.8%) and hand-foot syndrome (11.8%) with TPC.
However, median treatment durations were substantially and consistently longer for OLA than for TPC, and there were fewer treatment discontinuations because of toxicity for OLA than for TPC. At the time of data cutoff, 43 patients in the OLA group and 1 patient in the TPC cohort remained on treatment.
How these results influence practice
The results of the SOLO3 trial are clear: Treatment with OLA is a reasonable alternative to nonplatinum-containing chemotherapy for women with BRCA mutations and platinum-sensitive ovarian cancer. OLA is a “chemotherapy-free” option for these patients in the second- and later-line settings.
Less clear are the following:
- How many patients with BRCA mutations will not have already received a PARP inhibitor in the frontline maintenance setting in the future? SOLO3 required modification in the accrual target and endpoint because of challenges in patient recruitment from the entry of PARP inhibitors into routine clinical practice.
- Would OLA be superior to a carboplatin doublet rather than a nonplatinum single agent in patients with two prior relapses of platinum-sensitive ovarian cancer? Standard practice would be for patients in the second-line setting to receive a platinum doublet.
- Is extending the platinum-free interval a worthwhile objective, or would some patients prefer a finite interval of a platinum doublet over an indefinite period of treatment with OLA?
All phase 3 clinical trials have limitations since they require years to complete and the applicability of the results are challenged by intercurrent advances in treatment options and diagnostic tests.
However, overall, the results of SOLO3 are impressive and should influence clinical practice for the subset of relapsed ovarian cancer patients who would have qualified to participate in it. OLA represents an important treatment advance for a group of patients who are trying to string together remission after remission, with limited negative impact on quality of life.
Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
In this edition of “Applying research to practice,” I highlight a study suggesting olaparib is helpful in patients BRCA mutations experiencing multiple relapses of ovarian cancer.
SOLO3 was the first phase 3 trial comparing the oral PARP inhibitor olaparib (OLA; 300 mg twice daily) with physician’s choice of intravenous single-agent chemotherapy (TPC) in relapsed high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer (J Clin Oncol. 2020 Feb 19. doi: 10.1200/JCO.19.02745).
The trial involved 266 BRCA-mutated patients who had received two (approximately 50%) or more lines of platinum-based TPC. All patients were required to be completely platinum sensitive (progression beyond 12 months from last platinum exposure) or partially platinum sensitive (progression within 6-12 months).
Women were randomized to receive either OLA or nonplatinum TPC (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). After an amendment to the study in 2017, the primary endpoint was objective response rate, determined by blinded independent central review, with a variety of secondary endpoints.
Among 223 patients with measurable disease, the objective response rate was 72.2% with OLA and 51.4% with TPC (odds ratio, 2.53; P = .002). Across all patients, the median progression-free survival was significantly better with OLA (13.4 months) than with TPC (9.2 months; P = .013). Overall survival data were immature.
The superiority of OLA for the primary endpoint was maintained in multiple subgroups of patients, including those who had received only two prior lines of therapy (OR, 3.44) and those who had three or more prior lines (OR, 2.21). Time to first subsequent therapy (HR, 0.48) and time to treatment discontinuation or death (HR, 0.17) were significantly longer for OLA than for TPC.
Adverse events were consistent with the established safety profiles of OLA and chemotherapy. The most common grade 3 or higher adverse events were anemia (21.3%) with OLA and neutropenia (15.8%) and hand-foot syndrome (11.8%) with TPC.
However, median treatment durations were substantially and consistently longer for OLA than for TPC, and there were fewer treatment discontinuations because of toxicity for OLA than for TPC. At the time of data cutoff, 43 patients in the OLA group and 1 patient in the TPC cohort remained on treatment.
How these results influence practice
The results of the SOLO3 trial are clear: Treatment with OLA is a reasonable alternative to nonplatinum-containing chemotherapy for women with BRCA mutations and platinum-sensitive ovarian cancer. OLA is a “chemotherapy-free” option for these patients in the second- and later-line settings.
Less clear are the following:
- How many patients with BRCA mutations will not have already received a PARP inhibitor in the frontline maintenance setting in the future? SOLO3 required modification in the accrual target and endpoint because of challenges in patient recruitment from the entry of PARP inhibitors into routine clinical practice.
- Would OLA be superior to a carboplatin doublet rather than a nonplatinum single agent in patients with two prior relapses of platinum-sensitive ovarian cancer? Standard practice would be for patients in the second-line setting to receive a platinum doublet.
- Is extending the platinum-free interval a worthwhile objective, or would some patients prefer a finite interval of a platinum doublet over an indefinite period of treatment with OLA?
All phase 3 clinical trials have limitations since they require years to complete and the applicability of the results are challenged by intercurrent advances in treatment options and diagnostic tests.
However, overall, the results of SOLO3 are impressive and should influence clinical practice for the subset of relapsed ovarian cancer patients who would have qualified to participate in it. OLA represents an important treatment advance for a group of patients who are trying to string together remission after remission, with limited negative impact on quality of life.
Dr. Lyss was an oncologist and researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.