Observational study in R/M SCCHN V18Dec2018
Research type
Research Study
Full title
TREATMENT PATTERNS, CLINICAL OUTCOMES, RESOURCE UTILIZATION, AND PATIENT REPORTED OUTCOMES IN FIRST-LINE RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK (1L R/M SCCHN) PATIENTS IN EUROPE
IRAS ID
258057
Contact name
Prianka Singh
Contact email
Sponsor organisation
Bristol-Myers Squibb Research and Development
Duration of Study in the UK
0 years, 7 months, 0 days
Research summary
Research Summary
This research study will collect real-world data that would describe treatment patterns and, in particular, the rationale for therapy selection and discontinuation, patient characteristics and profiles in 1L R/M SCCHN therapy, and outcomes in this patient population. This is a two-cohort observational study as follows: \n• In summary for cohort 1, retrospective information (from patients being diagnosed between 01-Jan-2014 and 31-Dec-2016) will be entered in the eCRF. Patients that are alive and not lost to follow-up at time of data entry will be followed up at 24 weeks post study enrollment to ensure a minimum of 24 months of data censoring for death, following diagnosis of R/M SCCHN.\n• In summary, for cohort 2 patients will complete a questionnaire at study enrollment (baseline) and 15 weeks later they have to complete the same questionnaire again.
Summary of Results
Demographics Patients were on average 62.4 years, were tobacco users (83.2%) and, alcohol users (69.2%). The majority were not given an ECOG performance status designation. > 80% had Stage IV disease at the time of advanced diagnosis. At the time this study was conducted, PD-L1 and EGFR expression testing was not standard of care in clinical practice. Thus no data were available. (Table 1) Table 1. Demographics, Disease Characteristics and Risk Factors Total N = 203 Age at R/M diagnosis Mean (SD)
62.4 (10.2)
Median (range)
63 (29, 89)
Tobacco use, n (%)
84
83.2%
Yes
135
66.5%
Unknown
45
22.2%
Alcohol use, n (%)
106
69.2%
Human papilloma virus tested, n (%)
27
13.3%
Positive
9
33.3%
Site of primary tumor, n (%)
Oral cavity
67
33.0%
Oral pharynx
67
33.0%
Larynx
35
17.2%
Hypopharynx
34
16.7%
Stage at diagnosis, n (%)
II
22
10.8%
III
18
8.9%
IVA
79
38.9%
IVB
22
10.8%
IBC
62
30.5%
Non-interventional Study Summary CA209-8HX Nivolumab
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Total
N = 203
Sites of metastasis, n (%)
Lung
49
24.1%
Liver
5
2.5%
Bone
7
3.4%
Lymph nodes
17
8.4%
ECOG performance status at diagnosis, n (%)
0
35
17.2%
1
36
17.7%
2
19
9.4%
3
3
1.5%
Unknown
110
54.2%
PD-L1 expression tested*
0
0%
EGFR expression tested*
1
0.5%
DE = Germany, FR=France, UK = United Kingdom, R/M SCCHN = Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck, SD = standard deviation.
*EGFR and PD-L1 expression testing was not a part of routine practice during the time of treatment Non-interventional Study Summary CA209-8HX Nivolumab
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5.2 Treatment Patterns
At 1L treatment initiation for R/M SCCHN, 54% were platinum naïve/de novo metastatic, 16% were deemed platinum sensitive, and the remainder were platinum refractory or unknown. EXTREME (Cetuximab+Cisplatin+5-Fluorouracil) was administered to 32%, 33% received platinum combination therapy with/without a taxane, 19% received platinum monotherapy, 7% received other cetuximab-based therapy. A little over one-third went on to a second line of therapy. (Table 2) Table 2: R/M SCCHN 1L – Treatment Patterns Cohort 1 N = 203 Time to therapy from R/M diagnosis (weeks) Median (range)
7.0
1 - 130
Platinum status, n (%)
Platinum naïve or de novo metastatic
110
54.2%
Platinum Sensitive
33
16.3%
Platinum Refractory
20
9.9%
Unknown
40
19.7%
ECOG performance status at 1L initiation, n (%)
0
28
13.8%
1
41
20.2%
2
19
9.4%
3
3
1.5%
Unknown
112
55.2%
Duration of therapy from initiation (weeks) Median (range)
6.4
0, 78
Regimen, n (%)
EXTREME (Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil), n (%)
65
32.0%
Non-interventional Study Summary CA209-8HX Nivolumab
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Cohort 1
N = 203
Nivolumab, n (%)
1
0.5%
Other doublet, triplet, single agent therapies, n (%) Platinum monotherapy
39
19.2%
Platinum+5FU
23
11.3%
Cetuximab monotherapy
16
7.9%
Platinum + Cetuximab + Capecitabine
13
6.4%
Platinum + Capecitabine
10
4.9%
Platinum + Cetuximab
10
4.9%
Taxane monotherapy
8
3.9%
Platinum + Taxane
6
3.0%
Platinum + Taxane + 5FU
5
2.5%
5FU monotherapy
3
1.5%
Other
2
1.0%
Cetuximab + Taxane
1
0.5%
Platinum + Taxane + Cetuximab
1
0.5%
Underwent surgical resection, n (%)
103
50.7%
Received radiation, n (%)
105
51.7%
Received a second line of therapy, n (%)
70
34.5%
5-FU = 5-Fluorouracil, R/M SCCHN = Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck, ECOG = Eastern Cooperative Oncology Group Non-interventional Study Summary CA209-8HX Nivolumab
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5.3 Clinical Outcomes
Objective response to 1L therapy was 32.5%. Median duration of response from date of first response was 6.7 months (95% CI: 3.2, 10.2). Landmark 6, 12, 24- and 36-month OS was 68.7%, 39.7%, 24.2% and 19.6%, respectively. Median OS from date of 1L initiation was 10.0 months (95% CI: 8.2, 11.8). Landmark 6, 12, 24- and 36-month PFS was 50.3%, 24.8%, 24.2% and 19.3%, respectively. Median PFS from date of 1L initiation was 6.2 months (95% CI: 5.3, 7.2). (Table 3) Table 3: R/M SCCHN 1L – ORR, Response and Survival Cohort 1 N = 203 ORR, n (%)
66
32.5%
Complete
20
9.9%
Partial
48
23.6%
Stable disease
29
14.3%
Progressive disease
58
28.6%
Unknown
48
23.6%
Overall survival from 1L initiation, n (%) (95% CI)
6 months
68.7%
(61.7, 74.7)
12 months
39.7%
(32.8, 46.5)
24 months
19.6%
(14.2, 25.5)
36 months
13.0%
(8.5, 18.5)
Progression free survival from 1L initiation, %, (95% CI)
6 months
50.3%
(43.1, 57.1)
12 months
28.4%
(18.1, 30.5)
24 months
19.3%
(13.8, 25.5)
36 months
**
OS median, 95% CI
10.0 (8.2, 11.8)
PFS median, 95% CI
6.2 (5.3, 7.2)
DOR median, 95% CI
6.7 (3.2, 10.2)
R/M SCCHN = Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck, ORR = objective response rate, OS = overall survival, PFS = progression free survival, CI = confidence interval, DOR= Duration of Response Non-interventional Study Summary CA209-8HX Nivolumab
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6 STRENGTHS AND LIMITATIONS
This study describes the real-world experience of patients being treated for R/M SCCHN in the UK, France, and Germany. Results shed light on the demographics, clinical characteristics, and treatment patterns of patients with R/M SCCHN outside of the context of clinical trials.
Due to the difficulty enrolling patients, the desired sample size was not achieved in the chart review portion of the study. This limited the analyses that could be performed. The scientific and systematic investigation of existing health records is an important and valued method in healthcare research, specifically in epidemiology and quality assessment studies. Limitations to retrospective chart review research include incomplete or missing documentation in patient charts and the fact that causality cannot be established.
Study results are generalizable only to the R/M SCCHN patients who were diagnosed during the study period, so extrapolation to other R/M SCCHN diagnosis periods will be limited to understanding changes in disease management and treatment in these patient populations. Due to delays in data collection, new treatments have entered the therapeutic area, so results may not be reflective of current practice. As physicians may not use standardized criteria for response to therapy, objective response may not be consistent with clinical-trial criteria.
To minimize the risk of study patients being identified, we capture only month and year for date of diagnosis, date of therapy initiations and discontinuations, date of last follow-up, and date of death. We do not capture gender. Therefore, some analyses including calculations relying upon dates (e.g., duration of response, overall survival) are approximations.
Treatment patterns represent only the practices of physicians who have agreed to participate in the study, and may vary from non-responding physicians, i.e., those who refused to participate in the study and/or those who failed to complete the patient forms on time.
We were unable to complete the PRO portion of the study due to inability to enroll patients. Although physicians seek to record all patient experiences in the medical charts, there may be some undercounting of events that have occurred outside the office and are therefore underrepresented in the absence of reliable patient reported data.REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
19/YH/0203
Date of REC Opinion
2 Sep 2019
REC opinion
Further Information Favourable Opinion