OVAR 16 QOL Update Health-Related Quality of Life Secondary - - PowerPoint PPT Presentation

OVAR 16 QOL Update

Health-Related Quality of Life

Secondary endpoint: evaluate health-related quality of life (HRQOL) as measured by EORTC QLQ-C30, OV28 and EQ-5D

(captures health status across five dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression)

• Data were collected at baseline, week 13,

months 7, 10, 13, 16, 25 (end of treatment), and 31 (post-treatment)

Pre-specified analyses examined HRQOL differences while on treatment

Mixed-model repeated measures analysis

Exploratory Hypotheses

Maintenance therapy with pazopanib will result in a small but statistically significant decline in global HRQOL and more side effects during the time on treatment, but will be associated with an overall benefit to patients Specifically:

Pazopanib will be associated with superior quality adjusted PFS Progressive disease results in a decline in quality of life Pazopanib will delay the time to second line therapy

Proportion of EQ-5D Questionnaires Completed

Progression-free (PF) Population Intent-to-treat (ITT) Population

BL Wk13 M7 M10 M13 M16 M25 Study Visit

• n treatment
• ff treatment

BL Wk13 M7 M10 M13 M16 M25 Study Visit PF on treatment PF off treatment PP 99% 98% 99% 98% 98% 98% 100% 94% 84% 74% 57% 47% 36% 24% % of PF Population

100 90 80 70 60 50 40 30 20 10

% of ITT Population

100 90 80 70 60 50 40 30 20 10

Abbreviations: BL, baseline; M, month; PP, post-progression; Wk, week.

Prespecified Analyses per Protocol

Difference in change from baseline in HRQOL scores between treatment groups*

QLQ-C30 Global Health Status OV-28 subscales EQ-5D

*Mixed model repeated measure analysis Interpretation of clinical significance followed Cocks et al 2011 and Pickard et al 2007

QLQ-C30 Global Health Status

• 30
• 20
• 10

10 20 30 Adjusted Mean (± SE) Pazopanib Placebo Baseline W13 M7 M10 M13 M16 M25 Better Health Status

Abbreviations: M, month; SE, standard error of the mean; W, week.

EQ-5D Utility Index

Baseline W13 M7 M10 M13 M16 M25

• 0.3
• 0.2
• 0.1

0.1 0.2 0.3 Adjusted Mean (± SE) Pazopanib Placebo Better Utility

Abbreviations: M, month; SE, standard error of the mean; W, week.

QLQ-C30 Diarrhea (ITT)

• 30
• 20
• 10

10 20 30 Adjusted Mean (± SE) Pazopanib Placebo Baseline W13 M7 M10 M13 M16 M25 More Diarrhea

Abbreviations: ITT, intention-to-treat; M, month; SE, standard error of the mean; W, week.

Post Hoc / Exploratory Analyses

Evaluate the trade-offs between treatment efficacy and treatment-related toxicity

Quality-Adjusted PFS (QAPFS)

Proportion Progression-Free

1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Median 80 120 160 200 240 280 320 360 400 440 480 520 560 600 640 680 720

Days From Randomization

760 40

P = 0.052 (1000 x bootstrap with replacement)

Therapy Pazopanib: QAPFS Placebo: QAPFS

Post Hoc Analysis

QLQ-C30 after progression

QLQ-C30 Global Health Status (GHS) deteriorates with progression

8.6 points difference between pre- and post-progression (P < 0.0001)* *paired t-test; analysis included patients with pre- and post-progression data pooled across treatment arms (N=206)

Post Hoc Analysis Time to Subsequent Anticancer Therapy

Medians 19.7 vs 15.0 months for pazopanib and placebo, respectively Curves divergent at 24 months

Proportion Progression-Free

1.0 0.8 0.6 0.4 0.2 0.0 6 12 18

Time Since Randomization, Months

24 30 36

472 389 273 211 139 25 36 468 Pazopanib Placebo

HR (95% CI): 0.722 (0.698, 0.858) Log-rank P value=0.0001

Patients at risk

Pazopanib (n=472) Placebo (n=468)

384 253 195 133 32 3

Conclusions

Maintenance therapy with pazopanib results in

an improvement in median PFS of 5.6 months a small decrement in overall HRQOL for patients on treatment a significant increase in patient-reported diarrhea

Progression results in worse HRQOL and initiation of further chemotherapy Quality-adjusted PFS supports the net value of maintenance therapy Limitations of post-hoc analyses

highlight the importance of including a priori HRQOL hypotheses in future studies