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PARP inhibitors didn’t impair QOL as ovarian cancer maintenance therapy

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Patient-reported outcomes should be standard

The QOL analyses of these two trials clearly show that neither olaparib nor niraparib has a detrimental effect on QOL in the maintenance setting of platinum-sensitive recurrent ovarian cancer. Future trials of the maintenance setting of recurrent ovarian cancer should include a predefined patient reported outcome (PRO) hypothesis and a statistical analysis plan including appropriate timing and duration of measurements. The completion of PRO instruments can be a burden to patients; thus, limiting PROs to those that inform a study-specific hypothesis can aid in achieving a high compliance rate. For example, the effect of gastrointestinal symptoms on QOL by EQ-5D-5L [European QOL five-dimension five-level questionnaire] is difficult to assess. As other drug classes are incorporated into treatment regimens for recurrent ovarian cancer, the use of the same PRO measures between trials, such as the Measure of Ovarian Symptoms and Treatment, might help in comparison of the therapeutic regimens.

Daisuke Aoki, MD, and Tatsuyuki Chiyoda, MD, are with the department of obstetrics and gynecology at Keio University, Tokyo. Dr. Aoki disclosed personal fees from AstraZeneca. Dr. Chiyoda reported no conflicts of interest. Their remarks are adapted and condensed from an editorial published online July 16, 2018, in The Lancet Oncology.


 

FROM THE LANCET ONCOLOGY

Women with platinum-sensitive recurrent ovarian cancer who received maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor had no significant decreases in health-related quality of life, outcomes data from two randomized clinical trials show.

Health-related quality of life (HRQOL) analyses from the SOLO2/ENGOT-Ov-21 trial comparing olaparib (Lynparza) with placebo and the ENGOT-OV16/NOVA trial comparing niraparib (Zejula) with placebo as maintenance therapy in women with ongoing responses to their last platinum-based chemotherapy showed that neither agent had major detrimental effects on patient-reported outcomes, further supporting the progression-free survival benefits previously seen with each agent in its respective trials.

“These results show the significant benefit of maintenance olaparib to patients beyond the RECIST [Response Evaluation Criteria in Solid Tumors] definition of progression, the primary endpoint of SOLO2, and highlight the importance of including patient-centered outcomes in addition to HRQOL in trials of maintenance therapy, in line with the recommendations of the 5th Ovarian Cancer Consensus Conference,” wrote Michael Friedlander, MD, of the University of New South Wales Clinical School and Prince of Wales Hospital in Randwick, New South Wales, Australia, and his colleagues.

Similarly, Amit M. Oza, MD, of Princess Margaret Cancer Centre in Toronto, and his coinvestigators in the ENGOT-OV16/NOVA trial found that “niraparib has no significant negative effect on QOL in patients with recurrent ovarian cancer. Combined with the evidence of increased progression-free survival with niraparib in the maintenance setting, these findings support the addition of niraparib as a component of standard of care.”

Both studies were published online in The Lancet Oncology: Friedlander M et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30343-7, and Oza AM et al. Lancet Oncol 2018 Jul 16 doi: 10.1016/S1470-2045(18)30333-4.

SOLO2 QOL summary

In SOLO2, patients with a germline BRCA1 or BRCA2 mutation and platinum-sensitive ovarian cancer that relapsed after at least two lines of chemotherapy were randomly assigned to receive either oral olaparib 300 mg twice daily (196 patients) or placebo (99 patients).

The prespecified primary HRQOL analysis looked at the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer (FACT-O) Trial Outcome Index (TOI) score during the first 12 months of the study.

In addition, the investigators examined secondary planned QOL analyses, including duration of good quality of life, defined as time without significant symptoms of toxicity, or TWiST, and quality-adjusted progression-free survival (QAPFS).

The adjusted average mean change from baseline over the first 12 months in TOI was –2.90 with olaparib vs. –2.87 with placebo (nonsignificant).

In contrast, patients treated with olaparib had significantly better mean QAPFS (13.96 vs. 7.28 months) and TWiST (15.03 vs. 7.70 months) results.

“All these predefined endpoints support the benefit to patients of a prolongation of progression-free survival, which is the primary endpoint in maintenance trials in ovarian cancer, and should be routinely included in future trials,” wrote Dr. Friedlander and his associates.

ENGOT-OV16/NOVA QOL summary

Investigators for this trial enrolled patients into two independent cohorts based on germline BRCA mutations or lack thereof. In all, 138 patients were assigned to niraparib and 65 to placebo in the germline BRCA mutation cohort, and 234 to niraparib and 116 to placebo in the nonmutation cohort.

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