Quality of life during olaparib maintenance therapy in

platinum-sensitive relapsed serous ovarian cancer

Supplementary material

Methods

Assessments

The Functional Assessment of Cancer Therapy Ovarian (FACT-O) questionnaire

includes the 27-item FACT-General (FACT-G version 4) questionnaire targeted toward

general cancer health-related quality of life (HRQoL) and 12 questions specific to issues

faced by ovarian cancer patients (Supplementary Figure 1a) (Basen-Engquist et al,

2001).

The items included in the Trial Outcome Index (TOI) (Supplementary Figure 1b) assess

the most relevant areas for patients with ovarian cancer and capture a patient’s ability to

lead a normal fulfilling life, as well as the impact of adverse events from treatment and

feeling ill (Cella et al, 1993).

FOSI assessment derives from eight symptom-related FACT-O items:

‘I have a lack of energy’

‘I have been vomiting’

‘I have pain’

‘I have nausea’

‘I have a swelling in my stomach area’

1

‘I worry that my condition will get worse’

’I am content with the quality of my life right now’

‘I have cramps in the stomach’

Nausea, vomiting and fatigue

For each item of nausea, vomiting or fatigue, patients were asked to score their

symptoms (not at all [4], a little bit [3], somewhat [2], quite a bit [1], and very much [0]),

with higher scores representing a more favourable health state.

Analyses

Based on pre-defined minimally important differences (MIDs), the proportion of patients

with a best response of ‘improved’, ‘no change’ and ‘worsened’ was calculated (Osoba

et al, 2005; Yost and Eton, 2005; Beaumont et al, 2007). Best response of ‘improved’

was defined as two visit responses of ‘improved’ a minimum of 21 days apart, without an

intervening visit response of ‘worsened’; best response of ‘no change’ used the same

criteria except that patients could report two visit responses of ‘no change’, or a

response of ‘no change’ and a response of ‘improved’. ‘No change’ was defined as a

change from baseline of greater than –7 (TOI), –3 (FOSI), –9 (FACT-O), but less than

+7 (TOI), +3 (FOSI), +9 (FACT-O). Best response of ‘worsened’ was defined as a visit

response of ‘worsened’ without a response of ‘improved’ or ‘no change’ within 21 days.

‘Worsened’ was defined as a change from baseline of less than or equal to –7 (TOI), –3

(FOSI), –9 (FACT-O). Best responses for individual concepts of nausea, vomiting and

fatigue used the same definitions as for the FACT-O questionnaire. Time to worsening

was determined from the date of randomization until the date when the MID worsening

2

criteria had been reached, without a response of ‘improved’ or ‘no change’ within

21 days. Time-to-worsening analyses were performed using Cox proportional hazards

models with the same factors as the primary analysis (Jewish ancestry, platinum

sensitivity and response to prior therapy). Logistic regression with the same factors was

used for the best response comparisons.

3

Supplementary Table 1. Compliance rate over time (%)

TOI FOSI FACT-O

Olaparib

(n=136)

Placebo

(n=129)

Olaparib

(n=136)

Placebo

(n=129)

Olaparib

(n=136)

Placebo

(n=129)

Baseline 85 87 86 89 84 86

Month 1 79 87 81 88 77 86

Month 2 80 80 81 82 79 80

Month 3 74 73 74 76 74 73

Month 4 68 73 68 73 68 72

Month 5 66 66 66 68 66 66

Month 6 60 66 61 66 60 66

Compliance rate was determined by the number of evaluable forms divided by the number of expected forms. Evaluable forms were those where ≥50% of questions were answered for each domain. Forms were expected to be completed at baseline, at the start of every 28 day cycle and at the time of withdrawal/confirmed RECIST progression.

4

Supplementary Table 2. Time to worsening of TOI, FOSI and FACT-O using Cox’s proportional hazards model for the overall

population, patients with BRCAm, and gBRCAm

TOI FOSI FACT-O

Overall

populationBRCAm gBRCAm

Overall

populationBRCAm gBRCAm

Overall

populationBRCAm gBRCAm

Olap

(n=115)

Pla

(n=111)

Olap

(n=64)

Pla

(n=53)

Olap

(n=45)

Pla

(n=37)

Olap

(n=117)

Pla

(n=115)

Olap

(n=66)

Pla

(n=56)

Olap

(n=46)

Pla

(n=39)

Olap

(n=114)

Pla

(n=111)

Olap

(n=63)

Pla

(n=53)

Olap

(n=45)

Pla

(n=37)

Events,

n (%)

64

(55.7)

56

(50.5)

33

(51.6)

29

(54.7)

21

(46.7)

23

(62.2)

77

(65.8)

67

(58.3)

45

(68.2)

35

(62.5)

28

(60.9)

28

(71.8)

72

(63.2)

63

(56.8)

39

(61.9)

31

(58.5)

27

(60.0)

24

(64.9)

Median

time to

worsening,

monthsa

3.8 4.6 5.7 3.7 7.4 3.6 2.8 3.7 2.8 3.7 3.7 3.3 2.8 4.6 3.2 4.4 3.2 3.7

Treatment effectb

Hazard

ratio

(95% CI)

1.08 (0.75, 1.55) 0.80 (0.48, 1.34) 0.54 (0.30, 0.99) 1.22 (0.88, 1.71) 1.15 (0.74, 1.81) 0.71 (0.42, 1.22) 1.16 (0.83, 1.64) 1.04 (0.65, 1.69) 0.84 (0.48, 1.48)

2-sided 0.68 0.4 0.05 0.23 0.53 0.21 0.39 0.87 0.55

5

p-value

aCalculated using the Kaplan-Meier technique; banalysis was performed using a Cox proportional hazards model with factors for treatment, ethnic descent, platinum sensitivity and response to final platinum therapy; Hazard ratio <1 favours olaparibCI Confidence interval; Olap, olaparib treatment; Pla, placebo treatment; TOI Trial outcome index

6

Supplementary Figure 1. (a) FACT-O components by subscale; (b) TOI subscales

7

Supplementary Figure 2. Change from baseline to 6 months for TOI for (a) the

overall population and (b) patients with a gBRCAm; FOSI for (a) the overall

population and (b) patients with a gBRCAm; FACT-O (a) the overall population and

(b) patients with a gBRCAm

8

9

Supplementary Figure 3. TOI change from baseline to 6 months for physical

wellbeing for (a) the overall population and patients with (b) BRCAm and

(c) gBRCAm; functional wellbeing for (d) the overall population and patients with

(e) BRCAm and (f) gBRCAm; and ovarian cancer concerns for (g) the overall

population and patients with (h) BRCAm and (i) gBRCAm

10

Supplementary Figure 4. Total score change from baseline to 6 months for nausea

for (a) the overall population and patients with (b) BRCAm and (c) gBRCAm;

vomiting for (d) the overall population and patients with (e) BRCAm and

(f) gBRCAm; and fatigue for (g) the overall population and patients with

(h) BRCAm and (i) gBRCAm

11

12

References

Basen-Engquist K, Bodurka-Bevers D, Fitzgerald MA, Webster K, Cella D, Hu S,

Gershenson DM (2001) Reliability and validity of the functional assessment of cancer

therapy-ovarian. J Clin Oncol 19: 1809-1817.

Beaumont J, Yount S, Lalla D, Lubeck D, Derynck M, Karlan B (2007) ASCO Annual

Meeting Proceedings Part I. J Clin Oncol 25:18S (June 20 supplement)

Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, Silberman M, Yellen SB,

Winicour P, Brannon J, . (1993) The Functional Assessment of Cancer Therapy scale:

development and validation of the general measure. J Clin Oncol 11: 570-579.

Osoba D, Bezjak A, Brundage M, Zee B, Tu D, Pater J (2005) Analysis and interpretation of

health-related quality-of-life data from clinical trials: basic approach of The National Cancer

Institute of Canada Clinical Trials Group. Eur J Cancer 41: 280-287.

Yost KJ, Eton DT (2005) Combining distribution- and anchor-based approaches to determine

minimally important differences: the FACIT experience. Eval Health Prof 28: 172-191.

13