Delaying surgery didn’t impact survival in early-stage cervical cancer

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Mon, 03/22/2021 - 09:32

Delaying surgery for up to 3 months had no adverse impact on overall survival in early-stage cervical cancer in a retrospective study of more than 4,700 women in the National Cancer Database.

Dimitrios Nasioudis, MD, of University of Pennsylvania, oncologist
Dr. Dimitrios Nasioudis

The 5-year overall survival rate was 85.7% among women who had radical hysterectomy and lymphadenectomy within 4 weeks of diagnosis, 86.6% among those who had the same surgery 4-8 weeks after diagnosis, and 89.6% among those who had surgery 8-12 weeks after diagnosis (P = .12).

“For patients with clinical stage I cervical carcinoma undergoing radical hysterectomy, we found no evidence of a detrimental effect of waiting time (up to 12 weeks from diagnosis) on overall survival,” the study investigators reported in a poster at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer.

The investigators looked at the issue of surgical wait times because of surgery delays due to the COVID-19 pandemic, according to investigator Dimitrios Nasioudis, MD, of the University of Pennsylvania in Philadelphia.

“We wanted to see if there was a real impact in the survival of patients,” Dr. Nasioudis said in an interview. He added that “many times, there is a question of when to perform surgery,” especially when patients need medical optimization.

Dr. Nasioudis called the findings “reassuring” and said “waiting up to 3 or 4 months is reasonable.”

Still, the investigators plan to validate the results with more granular patient-level institutional data, he said. Given the limits of the database, there was no information on tumor relapse or cause of death and no central pathology review.
 

Study details

The study included 4,782 patients who underwent primary radical hysterectomy with lymphadenectomy. Patients had clinical stage I adenocarcinoma, squamous, or adenosquamous carcinoma of the cervix, with no history of another tumor or other cervical surgery.

The median time to surgery was 34 days across the study population. Patients were divided into three groups according to the timing of their surgery:

  • Group 1 included 1,823 (38.1%) patients who had surgery less than 4 weeks from diagnosis.
  • Group 2 included 2,207 (46.2%) patients who had surgery 4-8 weeks from diagnosis.
  • Group 3 included 752 (15.7%) patients who had surgery 8-12 weeks from diagnosis.

Patients in group 1 had a higher rate of positive lymph nodes, compared with patients in groups 2 and 3 (18.4%, 15.6%, and 14.7%, respectively; P = .014). Patients in group 1 also had a higher incidence of lymphovascular space invasion (42.1%, 38.1%, and 33%; P = .007) and a higher rate of positive surgical margins (6.3%, 5.2%, and 3.9%; P = .047).

Group 1 patients “had more aggressive features,” which could explain why they had surgery within a month, Dr. Nasioudis said.

Patients in groups 3 and 2 were more likely to have government insurance, compared with patients in group 1 (35.6%, 31.6%, and 24.6%, respectively P < .001). Group 3 patients were more likely than those in groups 2 and 1 to have comorbidities (14.2%, 11.6%, and 10.5%; P = .29).

However, there were no survival differences between groups in a multivariate analysis controlling for confounders, which included tumor size, histology and extension, status of lymph nodes, receipt of radiotherapy, patient age, insurance, race, and comorbidities. Furthermore, in a stratified analysis based on tumor extent, the timing of surgery had no impact on survival.

Dr. Nasioudis said he suspects access to care was an issue for some women, and there were likely delays for medical optimization.

Access to gynecologic oncology services at the University of Pennsylvania is “pretty easy,” he said, so delays are usually related to medical optimization, but that’s not always the case in underserved areas of the United States.

There was no funding for this study, and the investigators didn’t have any disclosures.

aotto@mdedge.com

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Delaying surgery for up to 3 months had no adverse impact on overall survival in early-stage cervical cancer in a retrospective study of more than 4,700 women in the National Cancer Database.

Dimitrios Nasioudis, MD, of University of Pennsylvania, oncologist
Dr. Dimitrios Nasioudis

The 5-year overall survival rate was 85.7% among women who had radical hysterectomy and lymphadenectomy within 4 weeks of diagnosis, 86.6% among those who had the same surgery 4-8 weeks after diagnosis, and 89.6% among those who had surgery 8-12 weeks after diagnosis (P = .12).

“For patients with clinical stage I cervical carcinoma undergoing radical hysterectomy, we found no evidence of a detrimental effect of waiting time (up to 12 weeks from diagnosis) on overall survival,” the study investigators reported in a poster at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer.

The investigators looked at the issue of surgical wait times because of surgery delays due to the COVID-19 pandemic, according to investigator Dimitrios Nasioudis, MD, of the University of Pennsylvania in Philadelphia.

“We wanted to see if there was a real impact in the survival of patients,” Dr. Nasioudis said in an interview. He added that “many times, there is a question of when to perform surgery,” especially when patients need medical optimization.

Dr. Nasioudis called the findings “reassuring” and said “waiting up to 3 or 4 months is reasonable.”

Still, the investigators plan to validate the results with more granular patient-level institutional data, he said. Given the limits of the database, there was no information on tumor relapse or cause of death and no central pathology review.
 

Study details

The study included 4,782 patients who underwent primary radical hysterectomy with lymphadenectomy. Patients had clinical stage I adenocarcinoma, squamous, or adenosquamous carcinoma of the cervix, with no history of another tumor or other cervical surgery.

The median time to surgery was 34 days across the study population. Patients were divided into three groups according to the timing of their surgery:

  • Group 1 included 1,823 (38.1%) patients who had surgery less than 4 weeks from diagnosis.
  • Group 2 included 2,207 (46.2%) patients who had surgery 4-8 weeks from diagnosis.
  • Group 3 included 752 (15.7%) patients who had surgery 8-12 weeks from diagnosis.

Patients in group 1 had a higher rate of positive lymph nodes, compared with patients in groups 2 and 3 (18.4%, 15.6%, and 14.7%, respectively; P = .014). Patients in group 1 also had a higher incidence of lymphovascular space invasion (42.1%, 38.1%, and 33%; P = .007) and a higher rate of positive surgical margins (6.3%, 5.2%, and 3.9%; P = .047).

Group 1 patients “had more aggressive features,” which could explain why they had surgery within a month, Dr. Nasioudis said.

Patients in groups 3 and 2 were more likely to have government insurance, compared with patients in group 1 (35.6%, 31.6%, and 24.6%, respectively P < .001). Group 3 patients were more likely than those in groups 2 and 1 to have comorbidities (14.2%, 11.6%, and 10.5%; P = .29).

However, there were no survival differences between groups in a multivariate analysis controlling for confounders, which included tumor size, histology and extension, status of lymph nodes, receipt of radiotherapy, patient age, insurance, race, and comorbidities. Furthermore, in a stratified analysis based on tumor extent, the timing of surgery had no impact on survival.

Dr. Nasioudis said he suspects access to care was an issue for some women, and there were likely delays for medical optimization.

Access to gynecologic oncology services at the University of Pennsylvania is “pretty easy,” he said, so delays are usually related to medical optimization, but that’s not always the case in underserved areas of the United States.

There was no funding for this study, and the investigators didn’t have any disclosures.

aotto@mdedge.com

Delaying surgery for up to 3 months had no adverse impact on overall survival in early-stage cervical cancer in a retrospective study of more than 4,700 women in the National Cancer Database.

Dimitrios Nasioudis, MD, of University of Pennsylvania, oncologist
Dr. Dimitrios Nasioudis

The 5-year overall survival rate was 85.7% among women who had radical hysterectomy and lymphadenectomy within 4 weeks of diagnosis, 86.6% among those who had the same surgery 4-8 weeks after diagnosis, and 89.6% among those who had surgery 8-12 weeks after diagnosis (P = .12).

“For patients with clinical stage I cervical carcinoma undergoing radical hysterectomy, we found no evidence of a detrimental effect of waiting time (up to 12 weeks from diagnosis) on overall survival,” the study investigators reported in a poster at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer.

The investigators looked at the issue of surgical wait times because of surgery delays due to the COVID-19 pandemic, according to investigator Dimitrios Nasioudis, MD, of the University of Pennsylvania in Philadelphia.

“We wanted to see if there was a real impact in the survival of patients,” Dr. Nasioudis said in an interview. He added that “many times, there is a question of when to perform surgery,” especially when patients need medical optimization.

Dr. Nasioudis called the findings “reassuring” and said “waiting up to 3 or 4 months is reasonable.”

Still, the investigators plan to validate the results with more granular patient-level institutional data, he said. Given the limits of the database, there was no information on tumor relapse or cause of death and no central pathology review.
 

Study details

The study included 4,782 patients who underwent primary radical hysterectomy with lymphadenectomy. Patients had clinical stage I adenocarcinoma, squamous, or adenosquamous carcinoma of the cervix, with no history of another tumor or other cervical surgery.

The median time to surgery was 34 days across the study population. Patients were divided into three groups according to the timing of their surgery:

  • Group 1 included 1,823 (38.1%) patients who had surgery less than 4 weeks from diagnosis.
  • Group 2 included 2,207 (46.2%) patients who had surgery 4-8 weeks from diagnosis.
  • Group 3 included 752 (15.7%) patients who had surgery 8-12 weeks from diagnosis.

Patients in group 1 had a higher rate of positive lymph nodes, compared with patients in groups 2 and 3 (18.4%, 15.6%, and 14.7%, respectively; P = .014). Patients in group 1 also had a higher incidence of lymphovascular space invasion (42.1%, 38.1%, and 33%; P = .007) and a higher rate of positive surgical margins (6.3%, 5.2%, and 3.9%; P = .047).

Group 1 patients “had more aggressive features,” which could explain why they had surgery within a month, Dr. Nasioudis said.

Patients in groups 3 and 2 were more likely to have government insurance, compared with patients in group 1 (35.6%, 31.6%, and 24.6%, respectively P < .001). Group 3 patients were more likely than those in groups 2 and 1 to have comorbidities (14.2%, 11.6%, and 10.5%; P = .29).

However, there were no survival differences between groups in a multivariate analysis controlling for confounders, which included tumor size, histology and extension, status of lymph nodes, receipt of radiotherapy, patient age, insurance, race, and comorbidities. Furthermore, in a stratified analysis based on tumor extent, the timing of surgery had no impact on survival.

Dr. Nasioudis said he suspects access to care was an issue for some women, and there were likely delays for medical optimization.

Access to gynecologic oncology services at the University of Pennsylvania is “pretty easy,” he said, so delays are usually related to medical optimization, but that’s not always the case in underserved areas of the United States.

There was no funding for this study, and the investigators didn’t have any disclosures.

aotto@mdedge.com

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Rucaparib extends PFS in BRCA-mutated ovarian cancer, with an exception

Article Type
Changed
Tue, 03/23/2021 - 09:44

The PARP inhibitor rucaparib significantly improved progression-free survival (PFS) compared with standard-of-care chemotherapy in women with BRCA-mutated, advanced, relapsed ovarian cancer in the phase 3 ARIEL4 study.

Investigator-assessed PFS in both an intention-to-treat (ITT) analysis and an efficacy analysis that excluded patients with BRCA reversion mutations was 7.4 months in the rucaparib arm, compared with 5.7 months in patients who received either platinum-based chemotherapy or weekly paclitaxel.

Among the 23 patients with BRCA reversion mutations, however, investigator-assessed PFS was 2.9 months with rucaparib and 5.5 months with chemotherapy.

Overall survival data were not mature at the time of data cutoff in September 2020.

“Although the numbers are very small, the results suggest that presence of a BRCA reversion mutation may predict a reduced benefit from rucaparib,” said Rebecca Kristeleit, MBChB, PhD, of Guy’s and St. Thomas’ NHS Foundation Trust in London.

She presented the findings from ARIEL4 at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11479).

Invited discussant Ursula Matulonis, MD, of the Dana-Farber Cancer Institute in Boston, commented that the “BRCA reversion mutation data from ARIEL4 is intriguing. Strategies to overcome and better understand this type of resistance mechanism are needed.”
 

Study rationale and details

Rucaparib is approved as monotherapy for patients with BRCA-mutated, relapsed ovarian cancer who have received at least two prior lines of platinum-based chemotherapy. The approval was based on results of two phase 1/2 studies. ARIEL4 is a phase 3 confirmatory study, designed in consultation with both the U.S. Food and Drug Administration and the European Medicines Agency.

Women with relapsed, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer with deleterious germline or somatic BRCA mutations were eligible for enrollment in ARIEL4. The patients had to have received at least two lines of chemotherapy, including at least one platinum-based regimen, with no prior PARP inhibitor or single-agent paclitaxel treatment.

Overall, 95% of patients had epithelial ovarian cancer, 3% had fallopian tube cancer, and 2% had primary peritoneal cancer. About 90% of cancers were serous in histology. Most patients (84%) had germline BRCA mutations, 16% had somatic mutations, and the status was unknown in the remaining patients.

Patients were randomized on a 2:1 basis to receive rucaparib at 600 mg twice daily (n = 233) or chemotherapy (n = 116), stratified by platinum sensitivity status. Patients assigned to chemotherapy whose disease was considered platinum resistant or partially platinum sensitive were assigned to weekly paclitaxel. Patients with fully platinum-sensitive disease were assigned to platinum-based single-agent or doublet chemotherapy. Treatment cycles were 28 days.

On radiologically confirmed disease progression or unacceptable toxicity, patients assigned to chemotherapy had the option to cross over to the rucaparib arm. The follow-up portion of the study began 28 days after the last treatment dose, with visits every 8 weeks thereafter.

Baseline characteristics in the ITT population were similar between arms. There were 13 patients in the rucaparib arm and 10 in the chemotherapy arm who had BRCA reversion mutations and were excluded from the efficacy population.
 

Efficacy and safety

Investigator-assessed PFS in the efficacy population was a median of 7.4 months with rucaparib and 5.7 months with chemotherapy, translating to a hazard ratio (HR) of 0.64 (P = .001). In the ITT population, the respective median PFS intervals were identical, although with a slightly less favorable HR of 0.67 (P = .002). In the 23 patients with BRCA reversion mutations, the median PFS was worse with rucaparib, at 2.9 months, compared with 5.5 months for chemotherapy. This translated to a HR of 2.77, although the 95% confidence interval was wide and crossed 1, likely due to the small sample size.

Among patients who had measurable disease at baseline, the overall response rate in the efficacy population was 40.3% with rucaparib and 32.3% with chemotherapy, a difference that was not statistically significant (P = .13). The overall response data were similar in the ITT population (37.9% and 30.2%, respectively).

In the efficacy population, the duration of response was significantly longer in the rucaparib arm, at a median of 9.4 months versus 7.2 months (HR, 0.59; 95% CI, 0.36-0.98). The respective median response durations were identical in the ITT population, but the HR was 0.56 (95% CI, 0.34-0.93).

In both the efficacy and ITT populations, global health status was virtually identical and unchanged from baseline in both treatment arms through cycle 7.

Treatment-emergent adverse events (TEAEs) were more frequent with rucaparib. The most common TEAEs in the rucaparib and chemotherapy arms, respectively, were anemia/decreased hemoglobin (53.9% and 31.9%), nausea (53.4% and 31.9%), asthenia/fatigue (49.6% and 44.2%), ALT/AST increase (34.5% and 11.5%), and vomiting (34.1% and 16.8%).

In all, 8.2% of patients in the rucaparib arm and 12.4% of those in the chemotherapy arm discontinued therapy due to TEAEs.

Four patients in the rucaparib arm developed myelodysplastic syndrome or acute myeloid leukemia – one during treatment and three during follow-up. There were no cases of myelodysplastic syndrome or acute myeloid leukemia in patients who received chemotherapy.

“Data from ARIEL4 fits the paradigm that single-agent activity of PARP inhibitors in BRCA-mutated, recurrent ovarian cancer may be comparable to chemotherapy, and may, at times, be superior, depending on the study population, trial design, and treatment for control patients,” Dr. Matulonis said.

The study was funded by Clovis Oncology. Dr. Kristeleit disclosed relationships with Clovis, Roche, and Tesaro. Dr. Matulonis disclosed relationships with Novartis, Merck, and Immunogen.

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The PARP inhibitor rucaparib significantly improved progression-free survival (PFS) compared with standard-of-care chemotherapy in women with BRCA-mutated, advanced, relapsed ovarian cancer in the phase 3 ARIEL4 study.

Investigator-assessed PFS in both an intention-to-treat (ITT) analysis and an efficacy analysis that excluded patients with BRCA reversion mutations was 7.4 months in the rucaparib arm, compared with 5.7 months in patients who received either platinum-based chemotherapy or weekly paclitaxel.

Among the 23 patients with BRCA reversion mutations, however, investigator-assessed PFS was 2.9 months with rucaparib and 5.5 months with chemotherapy.

Overall survival data were not mature at the time of data cutoff in September 2020.

“Although the numbers are very small, the results suggest that presence of a BRCA reversion mutation may predict a reduced benefit from rucaparib,” said Rebecca Kristeleit, MBChB, PhD, of Guy’s and St. Thomas’ NHS Foundation Trust in London.

She presented the findings from ARIEL4 at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11479).

Invited discussant Ursula Matulonis, MD, of the Dana-Farber Cancer Institute in Boston, commented that the “BRCA reversion mutation data from ARIEL4 is intriguing. Strategies to overcome and better understand this type of resistance mechanism are needed.”
 

Study rationale and details

Rucaparib is approved as monotherapy for patients with BRCA-mutated, relapsed ovarian cancer who have received at least two prior lines of platinum-based chemotherapy. The approval was based on results of two phase 1/2 studies. ARIEL4 is a phase 3 confirmatory study, designed in consultation with both the U.S. Food and Drug Administration and the European Medicines Agency.

Women with relapsed, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer with deleterious germline or somatic BRCA mutations were eligible for enrollment in ARIEL4. The patients had to have received at least two lines of chemotherapy, including at least one platinum-based regimen, with no prior PARP inhibitor or single-agent paclitaxel treatment.

Overall, 95% of patients had epithelial ovarian cancer, 3% had fallopian tube cancer, and 2% had primary peritoneal cancer. About 90% of cancers were serous in histology. Most patients (84%) had germline BRCA mutations, 16% had somatic mutations, and the status was unknown in the remaining patients.

Patients were randomized on a 2:1 basis to receive rucaparib at 600 mg twice daily (n = 233) or chemotherapy (n = 116), stratified by platinum sensitivity status. Patients assigned to chemotherapy whose disease was considered platinum resistant or partially platinum sensitive were assigned to weekly paclitaxel. Patients with fully platinum-sensitive disease were assigned to platinum-based single-agent or doublet chemotherapy. Treatment cycles were 28 days.

On radiologically confirmed disease progression or unacceptable toxicity, patients assigned to chemotherapy had the option to cross over to the rucaparib arm. The follow-up portion of the study began 28 days after the last treatment dose, with visits every 8 weeks thereafter.

Baseline characteristics in the ITT population were similar between arms. There were 13 patients in the rucaparib arm and 10 in the chemotherapy arm who had BRCA reversion mutations and were excluded from the efficacy population.
 

Efficacy and safety

Investigator-assessed PFS in the efficacy population was a median of 7.4 months with rucaparib and 5.7 months with chemotherapy, translating to a hazard ratio (HR) of 0.64 (P = .001). In the ITT population, the respective median PFS intervals were identical, although with a slightly less favorable HR of 0.67 (P = .002). In the 23 patients with BRCA reversion mutations, the median PFS was worse with rucaparib, at 2.9 months, compared with 5.5 months for chemotherapy. This translated to a HR of 2.77, although the 95% confidence interval was wide and crossed 1, likely due to the small sample size.

Among patients who had measurable disease at baseline, the overall response rate in the efficacy population was 40.3% with rucaparib and 32.3% with chemotherapy, a difference that was not statistically significant (P = .13). The overall response data were similar in the ITT population (37.9% and 30.2%, respectively).

In the efficacy population, the duration of response was significantly longer in the rucaparib arm, at a median of 9.4 months versus 7.2 months (HR, 0.59; 95% CI, 0.36-0.98). The respective median response durations were identical in the ITT population, but the HR was 0.56 (95% CI, 0.34-0.93).

In both the efficacy and ITT populations, global health status was virtually identical and unchanged from baseline in both treatment arms through cycle 7.

Treatment-emergent adverse events (TEAEs) were more frequent with rucaparib. The most common TEAEs in the rucaparib and chemotherapy arms, respectively, were anemia/decreased hemoglobin (53.9% and 31.9%), nausea (53.4% and 31.9%), asthenia/fatigue (49.6% and 44.2%), ALT/AST increase (34.5% and 11.5%), and vomiting (34.1% and 16.8%).

In all, 8.2% of patients in the rucaparib arm and 12.4% of those in the chemotherapy arm discontinued therapy due to TEAEs.

Four patients in the rucaparib arm developed myelodysplastic syndrome or acute myeloid leukemia – one during treatment and three during follow-up. There were no cases of myelodysplastic syndrome or acute myeloid leukemia in patients who received chemotherapy.

“Data from ARIEL4 fits the paradigm that single-agent activity of PARP inhibitors in BRCA-mutated, recurrent ovarian cancer may be comparable to chemotherapy, and may, at times, be superior, depending on the study population, trial design, and treatment for control patients,” Dr. Matulonis said.

The study was funded by Clovis Oncology. Dr. Kristeleit disclosed relationships with Clovis, Roche, and Tesaro. Dr. Matulonis disclosed relationships with Novartis, Merck, and Immunogen.

The PARP inhibitor rucaparib significantly improved progression-free survival (PFS) compared with standard-of-care chemotherapy in women with BRCA-mutated, advanced, relapsed ovarian cancer in the phase 3 ARIEL4 study.

Investigator-assessed PFS in both an intention-to-treat (ITT) analysis and an efficacy analysis that excluded patients with BRCA reversion mutations was 7.4 months in the rucaparib arm, compared with 5.7 months in patients who received either platinum-based chemotherapy or weekly paclitaxel.

Among the 23 patients with BRCA reversion mutations, however, investigator-assessed PFS was 2.9 months with rucaparib and 5.5 months with chemotherapy.

Overall survival data were not mature at the time of data cutoff in September 2020.

“Although the numbers are very small, the results suggest that presence of a BRCA reversion mutation may predict a reduced benefit from rucaparib,” said Rebecca Kristeleit, MBChB, PhD, of Guy’s and St. Thomas’ NHS Foundation Trust in London.

She presented the findings from ARIEL4 at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11479).

Invited discussant Ursula Matulonis, MD, of the Dana-Farber Cancer Institute in Boston, commented that the “BRCA reversion mutation data from ARIEL4 is intriguing. Strategies to overcome and better understand this type of resistance mechanism are needed.”
 

Study rationale and details

Rucaparib is approved as monotherapy for patients with BRCA-mutated, relapsed ovarian cancer who have received at least two prior lines of platinum-based chemotherapy. The approval was based on results of two phase 1/2 studies. ARIEL4 is a phase 3 confirmatory study, designed in consultation with both the U.S. Food and Drug Administration and the European Medicines Agency.

Women with relapsed, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer with deleterious germline or somatic BRCA mutations were eligible for enrollment in ARIEL4. The patients had to have received at least two lines of chemotherapy, including at least one platinum-based regimen, with no prior PARP inhibitor or single-agent paclitaxel treatment.

Overall, 95% of patients had epithelial ovarian cancer, 3% had fallopian tube cancer, and 2% had primary peritoneal cancer. About 90% of cancers were serous in histology. Most patients (84%) had germline BRCA mutations, 16% had somatic mutations, and the status was unknown in the remaining patients.

Patients were randomized on a 2:1 basis to receive rucaparib at 600 mg twice daily (n = 233) or chemotherapy (n = 116), stratified by platinum sensitivity status. Patients assigned to chemotherapy whose disease was considered platinum resistant or partially platinum sensitive were assigned to weekly paclitaxel. Patients with fully platinum-sensitive disease were assigned to platinum-based single-agent or doublet chemotherapy. Treatment cycles were 28 days.

On radiologically confirmed disease progression or unacceptable toxicity, patients assigned to chemotherapy had the option to cross over to the rucaparib arm. The follow-up portion of the study began 28 days after the last treatment dose, with visits every 8 weeks thereafter.

Baseline characteristics in the ITT population were similar between arms. There were 13 patients in the rucaparib arm and 10 in the chemotherapy arm who had BRCA reversion mutations and were excluded from the efficacy population.
 

Efficacy and safety

Investigator-assessed PFS in the efficacy population was a median of 7.4 months with rucaparib and 5.7 months with chemotherapy, translating to a hazard ratio (HR) of 0.64 (P = .001). In the ITT population, the respective median PFS intervals were identical, although with a slightly less favorable HR of 0.67 (P = .002). In the 23 patients with BRCA reversion mutations, the median PFS was worse with rucaparib, at 2.9 months, compared with 5.5 months for chemotherapy. This translated to a HR of 2.77, although the 95% confidence interval was wide and crossed 1, likely due to the small sample size.

Among patients who had measurable disease at baseline, the overall response rate in the efficacy population was 40.3% with rucaparib and 32.3% with chemotherapy, a difference that was not statistically significant (P = .13). The overall response data were similar in the ITT population (37.9% and 30.2%, respectively).

In the efficacy population, the duration of response was significantly longer in the rucaparib arm, at a median of 9.4 months versus 7.2 months (HR, 0.59; 95% CI, 0.36-0.98). The respective median response durations were identical in the ITT population, but the HR was 0.56 (95% CI, 0.34-0.93).

In both the efficacy and ITT populations, global health status was virtually identical and unchanged from baseline in both treatment arms through cycle 7.

Treatment-emergent adverse events (TEAEs) were more frequent with rucaparib. The most common TEAEs in the rucaparib and chemotherapy arms, respectively, were anemia/decreased hemoglobin (53.9% and 31.9%), nausea (53.4% and 31.9%), asthenia/fatigue (49.6% and 44.2%), ALT/AST increase (34.5% and 11.5%), and vomiting (34.1% and 16.8%).

In all, 8.2% of patients in the rucaparib arm and 12.4% of those in the chemotherapy arm discontinued therapy due to TEAEs.

Four patients in the rucaparib arm developed myelodysplastic syndrome or acute myeloid leukemia – one during treatment and three during follow-up. There were no cases of myelodysplastic syndrome or acute myeloid leukemia in patients who received chemotherapy.

“Data from ARIEL4 fits the paradigm that single-agent activity of PARP inhibitors in BRCA-mutated, recurrent ovarian cancer may be comparable to chemotherapy, and may, at times, be superior, depending on the study population, trial design, and treatment for control patients,” Dr. Matulonis said.

The study was funded by Clovis Oncology. Dr. Kristeleit disclosed relationships with Clovis, Roche, and Tesaro. Dr. Matulonis disclosed relationships with Novartis, Merck, and Immunogen.

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