Many thanks for this important contribution to the discussion. We too have asked ourselves how important the marginal benefit for the patient is in view of the adverse effects.
Our study showed that doctors and healthy persons took a more critical view of adverse effects than melanoma patients (1). We asked whether patients would rather live symptom-free for eight weeks (receiving the best possible palliative care) or 16 weeks with moderately severe to very severe adverse effects (the average prolongation of life conferred by ipilimumab); the majority decided on the latter. In the face of a terminal illness, perspectives change and the remaining time left to live becomes more valuable. Documenting quality of life in the context of clinical studies also showed superiority for checkpoint therapy compared with the control arm (2), which is consistent with our own clinical experience. In the meantime data have shown that checkpoint inhibitor therapy in metastatic melanoma leads to long term survival in a proportion of patients without further therapy and adverse effects (3).
Furthermore, adequate management of adverse effects lowers morbidity and mortality. My co-authors and I have therefore taken every opportunity regionally, nationally, and internationally to speak on this subject, even if events were organized by the pharmaceutical industry. The increasing costs of modern oncologic drugs are problematic. In view of notably rising sales it is incomprehensible that the costs for checkpoint inhibitors are not falling drastically, because the manufacturing costs can be assumed to be negligible by comparison to the prices. This is a political problem that our healthcare system urgently needs to get a grip on. With regard to cost effectiveness, primary prevention of skin cancer is certainly the best measure—and too little is done in Germany in this regard. Not treating patients with skin cancer is not an option. Metastatic melanoma in comparatively young patients, with its often rapid progression, requires intensive care and support for patients, especially after the diagnosis has been made or if treatment has failed. It is especially in this phase that too few resources are available, in our opinion.
On behalf of the authors
Prof. Dr. med. Lucie Heinzerling, MPH
Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Conflict of interest statement
Prof. Heinzerling has served as a paid consultant for BMS, MSD, Roche, Novartis, Amgen, Curevac, Pierre Fabre, and Sanofi. She has received reimbursement of meeting attendance fees and travel expenses from BMS, Novartis, Roche, and Amgen and lecture honoraria from BMS, Amgen, MSD, Roche, and Novartis. She has received third-party funding for scientific research from Novartis, Curevac, BMS, MSD, Amgen, and Roche.
|1.||Krammer R, Heinzerling L: Therapy preferences in melanoma treatment—willingness to pay and preference of quality versus length of life of patients, physicians and healthy controls. PLOS ONE 2014; 9: e115317 CrossRef MEDLINE PubMed Central|
|2.||Schadendorf D, Dummer R, Hauschild A, et al.: Health-related quality of life in the randomised KEYNOTE-002 study of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory melanoma. Eur J Cancer 2016; 67: 46–5 CrossRefMEDLINE|
|3.||Schadendorf D, Hodi FS, Robert C, et al.: Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 2015; 33: 1889–9 CrossRef MEDLINE PubMed Central|
|4.||Heinzerling L, De Toni E, Schett G, Hundorfean G, Zimmer L: Checkpoint inhibitors—the diagnosis and treatment of side effects. Dtsch Arztebl Int 2019; 116: 119–26. VOLLTEXT|