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HONOLULU – The improved progression-free survival and reduced risk of disease progression seen with maintenance rucaparib versus placebo in women with recurrent ovarian cancer in the pivotal ARIEL3 study occurred across age subgroups, according to a post hoc exploratory analysis of data from the phase 3 study.
In general, the safety profile of the first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor was consistent across age groups, as well, but rates of dose modifications and treatment discontinuations varied slightly by age subgroup in the rucaparib (Rubraca)and placebo arms, Jonathan A. Ledermann, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
No clear trend emerged with respect to those differences, said Dr. Ledermann, a professor of medical oncology at University College of London Cancer Institute and UCL Hospitals.
Initial results from the randomized, placebo-controlled study were published in 2017 and showed a significant progression-free survival (PFS) benefit with 600 mg of maintenance rucaparib vs. placebo (10.8 vs. 5.4 months, respectively, in the intention-to-treat population). For the current analysis, outcomes were assessed for the ITT population across three baseline age-based subgroups: those under age 65 years, those aged 65-74 years, and those 75 years or older.
Investigator-assessed PFS – the primary endpoint of ARIEL3 – for the rucaparib vs. placebo groups was 11.1 vs. 5.4 months among 237 and 117 patients under age 65 years in the groups, respectively (hazard ratio, 0.33); 8.3 vs. 5.3 for 113 and 64 patients aged 65-74 years, respectively (HR, 0.43); and 9.2 and 5.5 months in 25 and 8 patients aged 75 and older (HR, 0.47), he said.
“The hazard ratios are comparable across all three age cohorts,” Dr. Ledermann said.
Treatment-emergent adverse events (TEAEs) of any grade occurring in at least 35% of patients included nausea, asthenia, vomiting, dysgeusia, constipation, anemia, ALT/AST increase, diarrhea, abdominal pain, thrombocytopenia, and pruritus.
The rates of these events were similar across age groups, although slight, nonsignificant numerical increases in grade 3 toxicities occurred with increasing age, he noted.
“If we look at dose interruption and dose reduction rates – again, broadly similar, [but with] a slight trend toward an increase in older age groups,” he said.
Dose modifications related to TEAEs, however, occurred in 65.5% of rucaparib and 9.4% of placebo patients aged under 65 years, compared with 82.3% and 12.5% of those aged 65-74, and 83.3% and 12.5% of those aged 75 or older, respectively. Discontinuations because of TEAEs occurred in 13.6% and 1.7% in those under age 65 years vs. 19.5% and 3.1% in those aged 65-74 years, and 20.8% and 0% of those aged 75 years or older in the groups, respectively.
Of note, the age subgroups and the treatment and placebo groups were well balanced except more of those under age 65 years had a deleterious germline or somatic BRCA mutation (96 and 49 in the rucaparib and placebo arms, respectively) than did patients aged 65-74 years (29 and 15, respectively), and patients aged 75 years and older (5 and 2, respectively).
ARIEL3 was funded by Clovis Oncology. Dr. Ledermann reported financial relationships (consulting, grant receipt, honorarial reimbursement, and/or speakers bureau fees) with AstraZeneca, Clovis Oncology, Pfizer, Seattle Genetics, Roche, and MSD/Merck.
SOURCE: Ledermann J et al. SGO 2019, Abstract 4.
HONOLULU – The improved progression-free survival and reduced risk of disease progression seen with maintenance rucaparib versus placebo in women with recurrent ovarian cancer in the pivotal ARIEL3 study occurred across age subgroups, according to a post hoc exploratory analysis of data from the phase 3 study.
In general, the safety profile of the first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor was consistent across age groups, as well, but rates of dose modifications and treatment discontinuations varied slightly by age subgroup in the rucaparib (Rubraca)and placebo arms, Jonathan A. Ledermann, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
No clear trend emerged with respect to those differences, said Dr. Ledermann, a professor of medical oncology at University College of London Cancer Institute and UCL Hospitals.
Initial results from the randomized, placebo-controlled study were published in 2017 and showed a significant progression-free survival (PFS) benefit with 600 mg of maintenance rucaparib vs. placebo (10.8 vs. 5.4 months, respectively, in the intention-to-treat population). For the current analysis, outcomes were assessed for the ITT population across three baseline age-based subgroups: those under age 65 years, those aged 65-74 years, and those 75 years or older.
Investigator-assessed PFS – the primary endpoint of ARIEL3 – for the rucaparib vs. placebo groups was 11.1 vs. 5.4 months among 237 and 117 patients under age 65 years in the groups, respectively (hazard ratio, 0.33); 8.3 vs. 5.3 for 113 and 64 patients aged 65-74 years, respectively (HR, 0.43); and 9.2 and 5.5 months in 25 and 8 patients aged 75 and older (HR, 0.47), he said.
“The hazard ratios are comparable across all three age cohorts,” Dr. Ledermann said.
Treatment-emergent adverse events (TEAEs) of any grade occurring in at least 35% of patients included nausea, asthenia, vomiting, dysgeusia, constipation, anemia, ALT/AST increase, diarrhea, abdominal pain, thrombocytopenia, and pruritus.
The rates of these events were similar across age groups, although slight, nonsignificant numerical increases in grade 3 toxicities occurred with increasing age, he noted.
“If we look at dose interruption and dose reduction rates – again, broadly similar, [but with] a slight trend toward an increase in older age groups,” he said.
Dose modifications related to TEAEs, however, occurred in 65.5% of rucaparib and 9.4% of placebo patients aged under 65 years, compared with 82.3% and 12.5% of those aged 65-74, and 83.3% and 12.5% of those aged 75 or older, respectively. Discontinuations because of TEAEs occurred in 13.6% and 1.7% in those under age 65 years vs. 19.5% and 3.1% in those aged 65-74 years, and 20.8% and 0% of those aged 75 years or older in the groups, respectively.
Of note, the age subgroups and the treatment and placebo groups were well balanced except more of those under age 65 years had a deleterious germline or somatic BRCA mutation (96 and 49 in the rucaparib and placebo arms, respectively) than did patients aged 65-74 years (29 and 15, respectively), and patients aged 75 years and older (5 and 2, respectively).
ARIEL3 was funded by Clovis Oncology. Dr. Ledermann reported financial relationships (consulting, grant receipt, honorarial reimbursement, and/or speakers bureau fees) with AstraZeneca, Clovis Oncology, Pfizer, Seattle Genetics, Roche, and MSD/Merck.
SOURCE: Ledermann J et al. SGO 2019, Abstract 4.
HONOLULU – The improved progression-free survival and reduced risk of disease progression seen with maintenance rucaparib versus placebo in women with recurrent ovarian cancer in the pivotal ARIEL3 study occurred across age subgroups, according to a post hoc exploratory analysis of data from the phase 3 study.
In general, the safety profile of the first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor was consistent across age groups, as well, but rates of dose modifications and treatment discontinuations varied slightly by age subgroup in the rucaparib (Rubraca)and placebo arms, Jonathan A. Ledermann, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
No clear trend emerged with respect to those differences, said Dr. Ledermann, a professor of medical oncology at University College of London Cancer Institute and UCL Hospitals.
Initial results from the randomized, placebo-controlled study were published in 2017 and showed a significant progression-free survival (PFS) benefit with 600 mg of maintenance rucaparib vs. placebo (10.8 vs. 5.4 months, respectively, in the intention-to-treat population). For the current analysis, outcomes were assessed for the ITT population across three baseline age-based subgroups: those under age 65 years, those aged 65-74 years, and those 75 years or older.
Investigator-assessed PFS – the primary endpoint of ARIEL3 – for the rucaparib vs. placebo groups was 11.1 vs. 5.4 months among 237 and 117 patients under age 65 years in the groups, respectively (hazard ratio, 0.33); 8.3 vs. 5.3 for 113 and 64 patients aged 65-74 years, respectively (HR, 0.43); and 9.2 and 5.5 months in 25 and 8 patients aged 75 and older (HR, 0.47), he said.
“The hazard ratios are comparable across all three age cohorts,” Dr. Ledermann said.
Treatment-emergent adverse events (TEAEs) of any grade occurring in at least 35% of patients included nausea, asthenia, vomiting, dysgeusia, constipation, anemia, ALT/AST increase, diarrhea, abdominal pain, thrombocytopenia, and pruritus.
The rates of these events were similar across age groups, although slight, nonsignificant numerical increases in grade 3 toxicities occurred with increasing age, he noted.
“If we look at dose interruption and dose reduction rates – again, broadly similar, [but with] a slight trend toward an increase in older age groups,” he said.
Dose modifications related to TEAEs, however, occurred in 65.5% of rucaparib and 9.4% of placebo patients aged under 65 years, compared with 82.3% and 12.5% of those aged 65-74, and 83.3% and 12.5% of those aged 75 or older, respectively. Discontinuations because of TEAEs occurred in 13.6% and 1.7% in those under age 65 years vs. 19.5% and 3.1% in those aged 65-74 years, and 20.8% and 0% of those aged 75 years or older in the groups, respectively.
Of note, the age subgroups and the treatment and placebo groups were well balanced except more of those under age 65 years had a deleterious germline or somatic BRCA mutation (96 and 49 in the rucaparib and placebo arms, respectively) than did patients aged 65-74 years (29 and 15, respectively), and patients aged 75 years and older (5 and 2, respectively).
ARIEL3 was funded by Clovis Oncology. Dr. Ledermann reported financial relationships (consulting, grant receipt, honorarial reimbursement, and/or speakers bureau fees) with AstraZeneca, Clovis Oncology, Pfizer, Seattle Genetics, Roche, and MSD/Merck.
SOURCE: Ledermann J et al. SGO 2019, Abstract 4.
REPORTING FROM SGO 2019