Solving Unknown Primary cancER (SUPER) Established in 2014 National prospective cohort study 11 metropolitan and rural sites across Australia

Overall Project Aims To establish a cohort of CUP patients with associated biospecimens, clinical, quality of life and psychosocial data To determine the clinical management patterns when genomics test results provided to treating clinician To establish the experiences, quality of life, psychosocial needs of patients with CUP compared to a matched sample of patients with metastatic cancer of a known primary and investigate differences between rural vs urban CUP patients

1st patient recruited November 2013 SUPER – 31st March 2019 1st patient recruited November 2013 Site Total Peter Mac 131 Westmead 26 Nepean 15 Blacktown Flinders 14 Geelong 29 Warrnambool 11 Cabrini 6 Bendigo 22 Darwin Healthscope 5 Border MO TOTAL RECRUITMENT 294 Recruiting ~6 per month 294 participants in total Study target – 350 Total Recruitment

AIM 1 SUPER – Establishing a CUP cohort (1st April) 2019) Item Number Target = 350 294 (84%) 56 remaining Recruitment rate 6 per month on average Projection: 30th Nov 2019 Item Number Female (%) Age (SD) Rural (%) Deceased < 3 M (%) < 6 M < 9 M < 12 M Phase 1 [2013-15] 168 92 (55) 63 (13) 28 (17) 30 (18) 50 (30) 67 (40) 81 (48) Phase 2 [2017 – ] 128 68 (53) 65 (13) 51 (40) 11* (10) 18* (23) 20* (32) 23* (46) Combined 294 159 (54) 79 (27) 44* (15) 68* (28) 87* (38) 104* (48) Test Item Number Phase 2 data 128 samples   CCP Complete 81 (63%) Incomplete 41 (32%) Pending 6 (5%) SUPERDx 77 (60%) 44 (34%) 7 (6%) Combined Complete both 72 (56%) Incomplete both 36 (28%) Complete either 86 (67%) * Number of included participants vary in P2 data as their duration on study will vary according to when they where recruited

AIM 2 SUPER – Impacting clinical decisions Specific Aims: Describe the molecular landscape of CUP patients and correlate molecular test results with demographic and clinical characteristics Determine the impact site-of-origin and mutation profiling has had on treatment decisions taken by the treating clinician 13

Clinical impact of molecular testing Dr Tharani Sivakumaran Design: Pre/post survey of clinical management prior to and post receiving genomic results Analysis ongoing

Early Results: Phase I Likely site of origin: CUPguide CUPGuide was completed for ~78% (97 of 124) of samples Primary site prediction was made in ~87% (84 of 97) Predictions resulted in: a change in management in ~12% (10 of 84) confirmed current management in ~63% (53 of 84) Mutation profiling: CCP version 1 Comprehensive Cancer Panel (CCP) was completed in ~83% (103 of 124) Actionable gene mutations where identified in ~10% (10 of 103) Germline gene mutations were identified in 6% (6 of 103) a change in treatment for 30% (3 of 10) of patients because the targeted therapy was available.

AIM 3 SUPER – Quality of life and psychosocial needs Specifically, we seek: To establish reliable estimates for quality of life and psychosocial needs across the CUP illness trajectory To identify similarities and differences between CUP and non-CUP patients from baseline to 12-month follow-up To identify similarities and differences between urban and rural/regional CUP patients from baseline to 12-month follow-up

What do we know about the experience of CUP? Compared to known primaries, CUP patients were: less likely to receive written information about their type of cancer, diagnostic tests and any operations they had Less likely to understand the results of their tests Less likely to completely understand the explanation of their illness Less likely to feel their views were taken into account in treatment discussions

Communicating with CUP patients 86 oncologist responded. 99% prepared to make a diagnosis of CUP if no primary located BUT 27% prefer to provide a ‘best guess’ rather than CUP as an diagnostic entity 83% would assign a primary site to obtain PBS drug funding 62% did not have a specific treatment protocol for CUP Different ways of describing Dx: “No I don’t use CUP, I usually talk about my best guess primary” vs “The primary (parent) appears of have regressed but metastases(children) have grown”

METHODS Design A prospective, longitudinal study with matched control group at baseline CUP patients recruited from both urban and rural/regional Patient reported outcome data will be collected at baseline and at 3, 6, 9 and 12 months post-baseline (or to death).

Measures Physical, social and mental health Patient Reported Outcomes Measurement Interactive System (PROMIS®) : Anxiety; Depression; Fatigue; Pain Interference; Pain Intensity; Sleep Disturbance; Physical Function; Satisfaction with Social Roles and Activities Cancer-specific health-related quality of life EORTC Quality of Life Questionnaire – C30 (EORTC QLQ-C30) Medical communication/information and psychological needs: Needs Assessment for Advanced Lung Cancer Patients (NA-ALCP) Hopelessness : Hopelessness Assessment in Illness (HAI) Communication about and understanding of illness and treatment: a purpose-built questionnaire drawn from UK National Cancer Patient Experience Survey

Psychological distress in CUP patients: the role of communication Aim To investigate the impact of patient-oncologist communication practices and socio-demographic factors on the anxiety and depression of CUP patients Design Cross-sectional survey: data drawn from baseline data from SUPER study. Dr Kamil Wolyniec

Patients’ communication experiences Item Response scale Percentage How well do you feel you understand your cancer? Very well Well Not so well Not well at all 20% 43% 25% 12% Were you given written information about the type of cancer you had? Yes, and it was easy to understand Yes, but it was difficult to understand No, I was not given written information I did not need written information Don’t know/can’t remember 26% 9% 57% 7% 0% How do you feel about the way you were told you had advanced cancer? It was done sensitively It should have been done a bit more sensitively It should have been done a lot more sensitively 78% 16%

Results CUP patients who felt they understood their cancer very well reported lower levels of anxiety and depression than those who did not. Patient’s understanding of cancer Patient’s understanding of cancer p=.006 p=.029 p=.004 p=.040 p=.006 Mean Anxiety scores Mean Depression scores Very well well Very well well Not so well Not well at all Not so well Not well at all

Key findings Only 20% felt they understood their cancer very well and this was linked to lower levels of anxiety and depression Less than half received written information about cancer or information about support but not linked to psychological distress. Younger CUP patients reported higher anxiety and depression 28

Conclusions Locating and retaining CUP patients in a cohort study remains challenging; as is successful genomic testing Rapid advances in genomic testing to assist in the diagnosis and treatment but at present these advances don’t appear to be translating into clinical management change Genomic testing advances represent a challenge for both clinician communication and patient understanding Good patient understanding may alleviate psychological distress Younger patients may require additional support and referral to psychological services