Lari Wenzel

Quality of Life and Adverse Events: Prognostic Relationships in Long-Term Ovarian Cancer Survival

Abstract Background There is a critical need to identify patient characteristics associated with long-term ovarian cancer survival. Methods Quality of life (QOL), measured by the Functional Assessment of Cancer Therapy-Ovarian-Trial Outcome Index (FACT-O-TOI), including physical, functional, and ovarian-specific subscales, was compared between long-term survivors (LTS) (8+ years) and short-term survivors (STS) (<5 years) of GOG 218 at baseline; before cycles 4, 7, 13, 21; and 6 months post-treatment using linear and longitudinal mixed models adjusted for covariates. Adverse events (AEs) were compared between survivor groups at each assessment using generalized linear models. All P values are 2-sided. Results QOL differed statistically significantly between STS (N = 1115) and LTS (N = 260) (P < .001). Baseline FACT-O-TOI and FACT-O-TOI change were independently associated with long-term survival (odds ratio = 1.05, 95% confidence interval = 1.03 to 1.06 and odds ratio = 1.06, 95% confidence interval = 1.05 to 1.07, respectively). A 7-point increase in baseline QOL was associated with a 38.0% increase in probability of LTS, and a 9-point increase in QOL change was associated with a 67.0% increase in odds for LTS. QOL decreased statistically significantly with increasing AE quartiles (cycle 4 quartiles: 0-5 vs 6-8 vs 9-11 vs ≥12 AEs, P = .01; cycle 21 quartiles: 0-2 vs 3 vs 4-5 vs ≥6 AEs, P = .001). Further, LTS reported statistically significantly better QOL compared with STS (P = .03 and P = .01, cycles 4 and 21, respectively), with similar findings across higher AE grades. Conclusions Baseline and longitudinal QOL change scores distinguished LTS vs STS and are robust prognosticators for long-term survival. Results have trial design and supportive care implications, providing meaningful prognostic value in this understudied population.

Effects of the WRITE Symptoms Interventions on Symptoms and Quality of Life Among Patients With Recurrent Ovarian Cancers: An NRG Oncology/GOG Study (GOG-0259)

PURPOSE GOG-259 was a 3-arm randomized controlled trial of two web-based symptom management interventions for patients with recurrent ovarian cancer. Primary aims were to compare the efficacy of the nurse-guided (Nurse-WRITE) and self-directed (SD-WRITE) interventions to Enhanced Usual Care (EUC) in improving symptoms (burden and controllability) and quality of life (QOL). METHODS Patients with recurrent or persistent ovarian, fallopian, or primary peritoneal cancer with 3+ symptoms were eligible for the study. Participants completed baseline (BL) surveys (symptom burden and controllability and QOL) before random assignment. WRITE interventions lasted 8 weeks to develop symptom management plans for three target symptoms. All women received EUC: monthly online symptom assessment with provider reports; online resources; and every 2-week e-mails. Outcomes were evaluated at 8 and 12 weeks after BL. Repeated-measures modeling with linear contrasts evaluated group by time effects on symptom burden, controllability, and QOL, controlling for key covariates. RESULTS Participants (N = 497) reported mean age of 59.3 ± 9.2 years. At BL, 84% were receiving chemotherapy and reported a mean of 14.2 ± 4.9 concurrent symptoms, most commonly fatigue, constipation, and peripheral neuropathy. Symptom burden and QOL improved significantly over time ( P < .001) for all three groups. A group by time interaction ( P < .001) for symptom controllability was noted whereby both WRITE intervention groups had similar improvements from BL to 8 and 12 weeks, whereas EUC did not improve over time. CONCLUSION Both WRITE Intervention groups showed significantly greater improvements in symptom controllability from BL to 8 and BL to 12 weeks compared with EUC. There were no significant differences between Nurse-WRITE and SD-WRITE. SD-WRITE has potential as a scalable intervention for a future implementation study.

Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005

PURPOSE We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC). PATIENTS AND METHODS NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes. RESULTS Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib ( v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, –1.3 to 1.5, P = .8725). CONCLUSION The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

Testing the Combination of Cediranib and Olaparib in Comparison to Each Drug Alone or Other Chemotherapy in Recurrent Platinum-Resistant Ovarian Cancer

This randomized phase II/III trial studies how well cediranib maleate and olaparib work when given together or separately, and compares them to standard chemotherapy in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has returned (recurrent) after receiving chemotherapy with drugs that contain platinum (platinum-resistant) or continued to grow while being treated with platinum-based chemotherapy drugs (platinum-refractory). Cediranib maleate and olaparib may stop the growth of tumor cells by blocking enzymes needed for cell growth. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cediranib maleate and olaparib together may cause more damage to cancer cells when compared to either drug alone or standard chemotherapy.

Symptom Management in Patients With Recurrent or Persistent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

This randomized clinical trial is studying two different symptom management programs to see how well they work compared with usual care in patients with recurrent or persistent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Developing a symptom management plan may help relieve symptoms related to cancer or cancer treatment and help improve quality of life.