Cost and economic burden of adverse events associated with metastatic melanoma treatments in five countries

Figures & data

Figure 1. Study design. AE, adverse event; SHI, statutory health insurance.

Table 1. Epidemiological and treatment usage data from 5 countries.

	Australia	France	Germany	Italy	United Kingdom
1-year prevalence of melanoma, n^85–88	9198	6564	14,164	6980	10,136
Proportion with metastatic disease, n (%)	2124 (23.1)^89	381 (5.8)^90	1164 (8.2)^91	498 (7.1)*	2027 (20.0)^92
Number of patients treated per treatment type,† n (%)
Targeted therapy	642 (30.2)	147 (38.6)	388 (33.3)	170 (34.1)	754 (37.2)
Immunotherapy	703 (33.1)	57 (14.9)	401 (34.4)	184 (36.9)	629 (31.0)
Chemotherapy	779 (36.7)	177 (46.5)	375 (32.2)	144 (29.0)	644 (31.8)

* Data on file, GlaxoSmithKline (Collegeville, PA).

† Number of patients treated with each type of therapy (targeted, chemo-, or immunotherapy) was estimated from the Delphi interview for each country.

Table 2. List of the most common (>20% any grade or >5% grade 3 or higher) adverse events associated with chemotherapy (dacarbazine, paclitaxel and fotemustine), immunotherapy (ipilimumab), and targeted therapy (vemurafenib).

Adverse events	Grades
Chemotherapy (24 studies*)^5^,^38–61
Alopecia	1, 2
Anaphylaxis	3, 4
Anemia	1, 2
Nausea/vomiting	1, 2
Neutropenia/leukopenia	1, 2
Neutropenia/leukopenia	3, 4
Pain (extremity and back)	1, 2
Peripheral neuropathy	1, 2
Peripheral neuropathy	3, 4
Thrombocytopenia	1, 2
Thrombocytopenia	3, 4
Immunotherapy (6 studies)^4^,^62–66
Colitis	3, 4
Diarrhea	1, 2
Diarrhea	3, 4
Fatigue	1, 2
Hypophysitis (immune-related)	3, 4
Pruritus (immune-related)	1, 2
Nausea	1, 2
Targeted therapy (3 studies)^5^,^67^,^68
Alopecia	1, 2
Arthralgia	1, 2
Fatigue	1, 2
Hyperkeratosis	1, 2
Nausea	1, 2
Photosensitivity reaction	1, 2
Pruritus (non-immune related)	1, 2
Rash	1, 2
Rash	3, 4
Skin papilloma	1, 2
Squamous cell carcinoma of the skin including keratoacanthoma	3, 4

* Nine studies for dacarbazine, 10 for fotemustine, and five for paclitaxel.

Table 3. Top 10 most cost intensive adverse events (AE) (based on per event per patient) from the statutory health insurance perspective. Adverse events due to chemotherapy (dark grey), immunotherapy (light grey), and targeted therapy (white) are ranked from most expensive to least expensive. All AEs listed are grade 3 or 4 unless specified.

Rank	Australia	France	Germany	Italy	United Kingdom
1	Colitis	Colitis	Neutropenia/leukopenia	Neutropenia/leukopenia	Diarrhea
2	Diarrhea	Anaphylaxis	Colitis	Anaphylaxis	Colitis
3	Neutropenia/leukopenia	Hypophysitis immune-related	Diarrhea	Thrombocytopenia	Hypophysitis immune-related
4	Hypophysitis immune-related	Diarrhea	Thrombocytopenia	Hypophysitis immune-related	Squamous cell carcinoma
5	Anaphylaxis	Neutropenia/leukopenia	Hypophysitis immune-related	Peripheral neuropathy	Skin papilloma*
6	Squamous cell carcinoma	Thrombocytopenia	Anaphylaxis	Diarrhea	Hyperkeratosis*
7	Rash	Rash	Peripheral neuropathy	Anemia*	Peripheral neuropathy
8	Skin papilloma*	Squamous cell carcinoma	Rash	Colitis	Rash
9	Thrombocytopenia	Peripheral neuropathy	Squamous cell carcinoma	Rash	Diarrhea*
10	Hyperkeratosis*	Anemia*	Nausea/vomiting*	Squamous cell carcinoma	Thrombocytopenia

* Grade 1 or 2.

AE, adverse event. Dark grey, chemotherapy; light grey, immunotherapy; white, targeted therapy.

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