Neoadjuvant and adjuvant end-points in health technology assessment in oncology

Published:February 19, 2021DOI:


      • Tumour eradication and reduced risk of recurrence are important to patients.
      • Time-to-event end-points are commonly accepted in health technology assessment (HTA).
      • Pathological complete response is often not considered as patient-relevant in HTA.
      • Adoption of (neo)adjuvant end-points in HTA improves access to innovative therapies.


      Health technology assessment (HTA) of clinical and economic value of a new intervention is an integral step in providing the access of patients to innovative cancer care and treatment. Overall survival (OS) is the preferred criterion for demonstrating the therapeutic efficacy in HTA given its direct clinical and patient relevance. However, with often long life expectancy of patients with early cancer, analysis of OS becomes less practical. Partially due to this reason, pathological complete response (pCR) and time-to-event end-points like disease-free survival are frequently incorporated into the pivotal clinical trials in the neoadjuvant and adjuvant settings. However, there exists a discrepancy between different national HTA bodies regarding the acknowledgement of patient relevance of these end-points. In this article, we analysed the perspectives of patients on different aspects of end-points used in clinical trials in early cancer. Gathered evidence strongly suggests that complete tumour eradication and reduced risk of recurrence provide important psychological benefits thus signifying that pCR and time-to-event end-points are directly relevant to patients. Additionally, we reviewed opinions on patient relevance of neoadjuvant and adjuvant therapy end-points adopted by HTA bodies during the recent evaluations. We found that improvements in end-points used in the adjuvant setting were commonly considered as valuable to patients. In contrast, opinions on patient relevance of neoadjuvant therapy end-points varied between the national HTA bodies. Universal acknowledgement of patient relevance of therapeutic end-points for early cancer by HTA bodies is necessary to balance the inequality in uptake of innovative therapies into national healthcare systems.


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        • Koedoot C.G.
        • de Haan R.J.
        • Stiggelbout A.M.
        • Stalmeier P.F.
        • de Graeff A.
        • Bakker P.J.
        • et al.
        Palliative chemotherapy or best supportive care? A prospective study explaining patients’ treatment preference and choice.
        Br J Canc. 2003; 89: 2219-2226
        • FDA
        Clinical trial endpoints for the approval of cancer drugs and biologics, Guidance for Industry.
        2018 ([cited 2019 September]; Available from:)
        • EMA
        Guideline on the evaluation of anticancer medicinal products in man.
        2017 ([cited 2019 September]; Available from:)
        • Hwang T.
        • Vokinger K.
        • Tibau A.
        • Gyawali B.
        • Naci H.
        • Franklin J.M.
        • et al.
        1555O_PRMagnitude of clinical benefit of cancer drugs and time to health technology assessment (HTA) decisions in Europe.
        Ann Oncol. 2018; 29
        • Allen N.
        • Walker S.R.
        • Liberti L.
        • Salek S.
        Health technology assessment (HTA) case studies: factors influencing divergent HTA reimbursement recommendations in Australia, Canada, England, and Scotland.
        Value Health. 2017; 20: 320-328
        • Allen N.
        • Liberti L.
        • Walker S.R.
        • Salek S.
        A comparison of reimbursement recommendations by European HTA agencies: is there opportunity for further alignment?.
        Front Pharmacol. 2017; 8: 384
        • Feldman L.D.
        • Hortobagyi G.N.
        • Buzdar A.U.
        • Ames F.C.
        • Blumenschein G.R.
        Pathological assessment of response to induction chemotherapy in breast cancer.
        Canc Res. 1986; 46: 2578-2581
        • von Minckwitz G.
        • Untch M.
        • Blohmer J.U.
        • Costa S.D.
        • Eidtmann H.
        • Fasching P.A.
        • et al.
        Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes.
        J Clin Oncol. 2012; 30: 1796-1804
        • Cortazar P.
        • Zhang L.
        • Untch M.
        • Mehta K.
        • Costantino J.P.
        • Wolmark N.
        • et al.
        Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.
        Lancet. 2014; 384: 164-172
        • Spring L.M.
        • Fell G.
        • Arfe A.
        • Trippa L.
        • Greenup R.
        • Reynolds K.
        • et al.
        Pathological complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and mortality, stratified by breast cancer subtypes and adjuvant chemotherapy usage: individual patient-level meta-analyses of over 27,000 patients.
        2018 (Available from:)
        • Li Z.
        • Shan F.
        • Wang Y.
        • Zhang Y.
        • Zhang L.
        • Li S.
        • et al.
        Correlation of pathological complete response with survival after neoadjuvant chemotherapy in gastric or gastroesophageal junction cancer treated with radical surgery: a meta-analysis.
        PloS One. 2018; 13e0189294
        • Zhong L.P.
        • Zhang C.P.
        • Ren G.X.
        • Guo W.
        • William Jr., W.N.
        • Sun J.
        • et al.
        Randomized phase III trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus up-front surgery in locally advanced resectable oral squamous cell carcinoma.
        J Clin Oncol. 2013; 31: 744-751
        • Zhang X.R.
        • Liu Z.M.
        • Liu X.K.
        • Wang F.H.
        • Li Q.
        • Li H.
        • et al.
        Influence of pathologic complete response to neoadjuvant chemotherapy on long-term survival of patients with advanced head and neck squamous cell carcinoma.
        Oral Surg Oral Med Oral Pathol Oral Radiol. 2013; 115: 218-223
        • Petrelli F.
        • Coinu A.
        • Cabiddu M.
        • Ghilardi M.
        • Vavassori I.
        • Barni S.
        Correlation of pathologic complete response with survival after neoadjuvant chemotherapy in bladder cancer treated with cystectomy: a meta-analysis.
        Eur Urol. 2014; 65: 350-357
        • Menzies A.M.
        • Rozeman E.A.
        • Amaria R.N.
        • Huang A.C.C.
        • Scolyer R.A.
        • Tetzlaff M.T.
        • et al.
        Pathological response and survival with neoadjuvant therapy in melanoma: a pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC).
        J Clin Oncol. 2019; 37 (p. 9503-9503)
        • Rozeman E.A.
        • Reijers I.L.M.
        • Hoefsmit E.P.
        • Sikorska K.
        • Krijgsman O.
        • Wiel B.A.V.D.
        • et al.
        Twenty-four months RFS and updated toxicity data from OpACIN-neo: a study to identify the optimal dosing schedule of neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) in stage III melanoma.
        J Clin Oncol. 2020; 38 (p. 10015-10015)
        • Mouillet G.
        • Monnet E.
        • Milleron B.
        • Puyraveau M.
        • Quoix E.
        • David P.
        • et al.
        Pathologic complete response to preoperative chemotherapy predicts cure in early-stage non-small-cell lung cancer: combined analysis of two IFCT randomized trials.
        J Thorac Oncol. 2012; 7: 841-849
        • Chaft J.E.
        • Rusch V.
        • Ginsberg M.S.
        • Paik P.K.
        • Finley D.J.
        • Kris M.G.
        • et al.
        Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers.
        J Thorac Oncol. 2013; 8: 1084-1090
        • Betticher D.C.
        • Hsu Schmitz S.F.
        • Totsch M.
        • Hansen E.
        • Joss C.
        • von Briel C.
        • et al.
        Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study.
        Br J Canc. 2006; 94: 1099-1106
        • Hellmann M.D.
        • Chaft J.E.
        • William Jr., W.N.
        • Rusch V.
        • Pisters K.M.
        • Kalhor N.
        • et al.
        Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint.
        Lancet Oncol. 2014; 15: 42-50
        • Qu Y.
        • Emoto K.
        • Eguchi T.
        • Aly R.G.
        • Zheng H.
        • Chaft J.E.
        • et al.
        Pathologic assessment after neoadjuvant chemotherapy for NSCLC: importance and implications of distinguishing adenocarcinoma from squamous cell carcinoma.
        J Thorac Oncol. 2019; 14: 482-493
        • Cherny N.I.
        • Sullivan R.
        • Dafni U.
        • Kerst J.M.
        • Sobrero A.
        • Zielinski C.
        • et al.
        A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).
        Ann Oncol. 2015; 26: 1547-1573
        • Schnipper L.E.
        • Davidson N.E.
        • Wollins D.S.
        • Tyne C.
        • Blayney D.W.
        • Blum D.
        • et al.
        American society of clinical oncology statement: a conceptual framework to assess the value of cancer treatment options.
        J Clin Oncol. 2015; 33: 2563-2577
        • Sargent D.
        • Shi Q.
        • Yothers G.
        • Van Cutsem E.
        • Cassidy J.
        • Saltz L.
        • et al.
        Two or three year disease-free survival (DFS) as a primary end-point in stage III adjuvant colon cancer trials with fluoropyrimidines with or without oxaliplatin or irinotecan: data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, C-06, C-07 and C89803.
        Eur J Canc. 2011; 47: 990-996
        • Mauguen A.
        • Pignon J.P.
        • Burdett S.
        • Domerg C.
        • Fisher D.
        • Paulus R.
        • et al.
        Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients’ data.
        Lancet Oncol. 2013; 14: 619-626
        • Oba K.
        • Paoletti X.
        • Alberts S.
        • Bang Y.J.
        • Benedetti J.
        • Bleiberg H.
        • et al.
        Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: a meta-analysis.
        J Natl Cancer Inst. 2013; 105: 1600-1607
        • Michiels S.
        • Le Maitre A.
        • Buyse M.
        • Burzykowski T.
        • Maillard E.
        • Bogaerts J.
        • et al.
        Surrogate endpoints for overall survival in locally advanced head and neck cancer: meta-analyses of individual patient data.
        Lancet Oncol. 2009; 10: 341-350
        • Saad E.D.
        • Squifflet P.
        • Burzykowski T.
        • Quinaux E.
        • Delaloge S.
        • Mavroudis D.
        • et al.
        Disease-free survival as a surrogate for overall survival in patients with HER2-positive, early breast cancer in trials of adjuvant trastuzumab for up to 1 year: a systematic review and meta-analysis.
        Lancet Oncol. 2019; 20: 361-370
        • Suciu S.
        • Eggermont A.M.M.
        • Lorigan P.
        • Kirkwood J.M.
        • Markovic S.N.
        • Garbe C.
        • et al.
        Relapse-free survival as a surrogate for overall survival in the evaluation of stage II-III melanoma adjuvant therapy.
        J Natl Cancer Inst. 2018; 110
        • Blumenthal G.M.
        • Bunn Jr., P.A.
        • Chaft J.E.
        • McCoach C.E.
        • Perez E.A.
        • Scagliotti G.V.
        • et al.
        Current status and future perspectives on neoadjuvant therapy in lung cancer.
        J Thorac Oncol. 2018; 13: 1818-1831
        • Al-Ghazal S.K.
        • Fallowfield L.
        • Blamey R.W.
        Comparison of psychological aspects and patient satisfaction following breast conserving surgery, simple mastectomy and breast reconstruction.
        Eur J Canc. 2000; 36: 1938-1943
        • Berhili S.
        • Ouabdelmoumen A.
        • Sbai A.
        • Kebdani T.
        • Benjaafar N.
        • Mezouar L.
        Radical mastectomy increases psychological distress in young breast cancer patients: results of A cross-sectional study.
        Clin Breast Canc. 2019; 19: e160-e165
        • Ohsumi S.
        • Shimozuma K.
        • Morita S.
        • Hara F.
        • Takabatake D.
        • Takashima S.
        • et al.
        Factors associated with health-related quality-of-life in breast cancer survivors: influence of the type of surgery.
        Jpn J Clin Oncol. 2009; 39: 491-496
        • van den Heuve N.M.J.
        • Reijers I.L.M.
        • Versluis J.M.
        • Rozeman E.A.
        • Jóźwiak K.
        • Blommers K.H.
        • et al.
        Health-related quality of life in stage III melanoma patients treated with neoadjuvant ipilimumab and nivolumab followed by index lymph node excision only, compared to therapeutic lymph node dissection: first results of the PRADO trial.
        in: ASCO Virtual Scientific Program. American Society of Clinical Oncology, 2020
        • Bellavance E.C.
        • Kesmodel S.B.
        Decision-making in the surgical treatment of breast cancer: factors influencing women's choices for mastectomy and breast conserving surgery.
        Front Oncol. 2016; 6: 74
        • Thill M.
        • Pisa G.
        • Isbary G.
        Targets for neoadjuvant therapy – the preferences of patients with early breast cancer.
        Geburtshilfe Frauenheilkd. 2016; 76: 551-556
        • Pennisi A.
        • Kieber-Emmons T.
        • Makhoul I.
        • Hutchins L.
        Relevance of pathological complete response after neoadjuvant therapy for breast cancer.
        Breast Canc. 2016; 10: 103-106
        • von Minckwitz G.
        • Huang C.S.
        • Mano M.S.
        • Loibl S.
        • Mamounas E.P.
        • Untch M.
        • et al.
        Trastuzumab emtansine for residual invasive HER2-positive breast cancer.
        N Engl J Med. 2019; 380: 617-628
        • Masuda N.
        • Lee S.J.
        • Ohtani S.
        • Im Y.H.
        • Lee E.S.
        • Yokota I.
        • et al.
        Adjuvant capecitabine for breast cancer after preoperative chemotherapy.
        N Engl J Med. 2017; 376: 2147-2159
        • Ditsch N.
        • Untch M.
        • Thill M.
        • Muller V.
        • Janni W.
        • Albert U.S.
        • et al.
        AGO recommendations for the diagnosis and treatment of patients with early breast cancer: update 2019.
        Breast Care. 2019; 14: 224-245
        • Liu Y.
        • Perez M.
        • Schootman M.
        • Aft R.L.
        • Gillanders W.E.
        • Jeffe D.B.
        • et al.
        Correlates of fear of cancer recurrence in women with ductal carcinoma in situ and early invasive breast cancer.
        Breast Canc Res Treat. 2011; 130: 165-173
        • Kanatas A.
        • Humphris G.
        • Lowe D.
        • Rogers S.N.
        Further analysis of the emotional consequences of head and neck cancer as reflected by the Patients’ Concerns Inventory.
        Br J Oral Maxillofac Surg. 2015; 53: 711-718
        • Howren M.B.
        • Christensen A.J.
        • Karnell L.H.
        • Funk G.F.
        Psychological factors associated with head and neck cancer treatment and survivorship: evidence and opportunities for behavioral medicine.
        J Consult Clin Psychol. 2013; 81: 299-317
        • Battle D.
        • Hammers H.J.
        • Jonasch E.
        • Derweesh I.
        • George D.J.
        • Bex A.
        • et al.
        Anxiety and patients: perspectives on surveillance and adjuvant therapy in renal cell carcinoma.
        J Clin Oncol. 2018; 36 (p. 4571-4571)
        • Poulakis V.
        • Witzsch U.
        • de Vries R.
        • Moeckel M.
        • Becht E.
        Quality of life after surgery for localized renal cell carcinoma: comparison between radical nephrectomy and nephron-sparing surgery.
        Urology. 2003; 62: 814-820
        • Dieng M.
        • Kasparian N.A.
        • Cust A.E.
        • Costa D.S.J.
        • Tran A.
        • Butow P.N.
        • et al.
        Sensitivity of preference-based quality-of-life measures for economic evaluations in early-stage melanoma.
        JAMA Dermatol. 2018; 154: 52-59
        • Bell K.J.L.
        • Mehta Y.
        • Turner R.M.
        • Morton R.L.
        • Dieng M.
        • Saw R.
        • et al.
        Fear of new or recurrent melanoma after treatment for localised melanoma.
        Psycho Oncol. 2017; 26: 1784-1791
        • Sollner W.
        • Zingg-Schir M.
        • Rumpold G.
        • Mairinger G.
        • Fritsch P.
        Need for supportive counselling--the professionals’ versus the patients’ perspective. A survey in a representative sample of 236 melanoma patients.
        Psychother Psychosom. 1998; 67: 94-104
        • Tan J.D.
        • Butow P.N.
        • Boyle F.M.
        • Saw R.P.
        • O’Reilly A.J.
        A qualitative assessment of psychosocial impact, coping and adjustment in high-risk melanoma patients and caregivers.
        Melanoma Res. 2014; 24: 252-260
        • Vogel R.I.
        • Strayer L.G.
        • Engelman L.
        • Nelson H.H.
        • Blaes A.H.
        • Anderson K.E.
        • et al.
        Comparison of quality of life among long-term melanoma survivors and non-melanoma controls: a cross-sectional study.
        Qual Life Res. 2017; 26: 1761-1766
        • Schlesinger-Raab A.
        • Schubert-Fritschle G.
        • Hein R.
        • Stolz W.
        • Volkenandt M.
        • Holzel D.
        • et al.
        Quality of life in localised malignant melanoma.
        Ann Oncol. 2010; 21: 2428-2435
        • Kenne Sarenmalm E.
        • Ohlen J.
        • Oden A.
        • Gaston-Johansson F.
        Experience and predictors of symptoms, distress and health-related quality of life over time in postmenopausal women with recurrent breast cancer.
        Psycho Oncol. 2008; 17: 497-505
        • Tomich P.L.
        • Helgeson V.S.
        Cognitive adaptation theory and breast cancer recurrence: are there limits?.
        J Consult Clin Psychol. 2006; 74: 980-987
        • Oh S.
        • Heflin L.
        • Meyerowitz B.E.
        • Desmond K.A.
        • Rowland J.H.
        • Ganz P.A.
        Quality of life of breast cancer survivors after a recurrence: a follow-up study.
        Breast Canc Res Treat. 2004; 87: 45-57
        • Trudel-Fitzgerald C.
        • Savard J.
        • Ivers H.
        Evolution of cancer-related symptoms over an 18-month period.
        J Pain Symptom Manag. 2013; 45: 1007-1018
        • Kong H.
        • Kwon O.K.
        • Yu W.
        Changes of quality of life after gastric cancer surgery.
        J Gastric Canc. 2012; 12: 194-200
        • Win T.
        • Sharples L.
        • Wells F.C.
        • Ritchie A.J.
        • Munday H.
        • Laroche C.M.
        Effect of lung cancer surgery on quality of life.
        Thorax. 2005; 60: 234-238
        • Bezjak A.
        • Lee C.W.
        • Ding K.
        • Brundage M.
        • Winton T.
        • Graham B.
        • et al.
        Quality-of-life outcomes for adjuvant chemotherapy in early-stage non-small-cell lung cancer: results from a randomized trial, JBR.10.
        J Clin Oncol. 2008; 26: 5052-5059
        • Andersen B.L.
        • Shapiro C.L.
        • Farrar W.B.
        • Crespin T.
        • Wells-Digregorio S.
        Psychological responses to cancer recurrence.
        Cancer. 2005; 104: 1540-1547
        • Kenny P.M.
        • King M.T.
        • Viney R.C.
        • Boyer M.J.
        • Pollicino C.A.
        • McLean J.M.
        • et al.
        Quality of life and survival in the 2 years after surgery for non small-cell lung cancer.
        J Clin Oncol. 2008; 26: 233-241
        • Hodges L.J.
        • Humphris G.M.
        Fear of recurrence and psychological distress in head and neck cancer patients and their carers.
        Psycho Oncol. 2009; 18: 841-848
        • Faccio F.
        • Renzi C.
        • Giudice A.V.
        • Pravettoni G.
        Family resilience in the oncology setting: development of an integrative framework.
        Front Psychol. 2018; 9: 666
        • Schadendorf D.
        • Hauschild A.
        • Santinami M.
        • Atkinson V.
        • Mandala M.
        • Chiarion-Sileni V.
        • et al.
        Patient-reported outcomes in patients with resected, high-risk melanoma with BRAF(V600E) or BRAF(V600K) mutations treated with adjuvant dabrafenib plus trametinib (COMBI-AD): a randomised, placebo-controlled, phase 3 trial.
        Lancet Oncol. 2019; 20: 701-710
        • Noone A.M.
        • Howlader N.
        • Krapcho M.
        • Miller D.
        • Brest A.
        • Yu M.
        • et al.
        SEER cancer statistics review, 1975–2015.
        National Cancer Institute, 2018
        • Barbato M.T.
        • Bakos L.
        • Bakos R.M.
        • Prieb R.
        • Andrade C.D.
        Predictors of quality of life in patients with skin melanoma at the dermatology department of the Porto Alegre Teaching Hospital.
        An Bras Dermatol. 2011; 86: 249-256
        • Kelly B.
        • Raphael B.
        • Smithers M.
        • Swanson C.
        • Reid C.
        • McLeod R.
        • et al.
        Psychological responses to malignant melanoma. An investigation of traumatic stress reactions to life-threatening illness.
        Gen Hosp Psychiatr. 1995; 17: 126-134
        • Amiri-Kordestani L.
        • Wedam S.
        • Zhang L.
        • Tang S.
        • Tilley A.
        • Ibrahim A.
        • et al.
        First FDA approval of neoadjuvant therapy for breast cancer: pertuzumab for the treatment of patients with HER2-positive breast cancer.
        Clin Canc Res. 2014; 20: 5359-5364
        • G-BA
        Tragende Gründe zum Beschluss des Gemeinsamen Bundesausschusses über eine Änderung der Arzneimittel-Richtlinie (AM-RL): Anlage XII – Beschlüsse über die Nutzenbewertung von Arzneimitteln mit neuen Wirkstoffen nach § 35a SGB V - pertuzumab (neues Anwendungsgebiet).
        2016 ([cited 2019 September]; Available from:)
        • pCODR
        Final recommendation for pertuzumab (Perjeta) for neaoadjuvant breast cancer.
        2015 ([cited 2019 September]; Available from:)
        • NICE
        Pertuzumab for the neoadjuvant treatment of HER2-positive breast cancer, Technology appraisal guidance [TA424].
        2016 ([cited 2019 September]; Available from:)
        • NICE
        Pertuzumab for adjuvant treatment of HER2-positive early stage breast cancer.
        2019 ([cited 2019 September]; Available from:)
        • G-BA
        Anlage XII – Beschlüsse über die Nutzenbewertung von Arzneimitteln mit neuen Wirkstoffen nach § 35a SGB V – pertuzumab (neues Anwendungsgebiet: Brustkrebs, adjuvante Behandlung).
        2018 ([cited 2019 September]; Available from:)
        • pCODR
        Final recommendations for pertuzumab and trastuzumab for early breast cancer.
        2018 ([cited 2019 September]; Available from:)
        • G-BA
        Mündliche Anhörung gemäß 5. Kapitel § 19 Abs. 2 Verfahrensordnung des Gemeinsamen Bundesausschusses, Pertuzumab.
        2018 ([cited 2019 November]; Available from:)
        • Eggermont A.M.
        • Chiarion-Sileni V.
        • Grob J.J.
        • Dummer R.
        • Wolchok J.D.
        • Schmidt H.
        • et al.
        Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy.
        N Engl J Med. 2016; 375: 1845-1855
      1. European Commission approves Bristol-Myers Squibb's Opdivo (nivolumab) for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection. Available from:

      2. European Commission approves Novartis combination therapy Tafinlar® + Mekinist® for adjuvant treatment of BRAF V600 mutation-positive melanoma. [cited 2019 September]; Available from:

        • FDA
        FDA approves pembrolizumab for adjuvant treatment of melanoma.
        2019 ([cited 2019 September]; Available from:)
        • pCODR
        Final recommendation for pembrolizumab (Keytruda) for melanoma adjuvant therapy.
        2019 ([cited 2019 September]; Available from:)
        • pCODR
        Final recommendation for nivolumab (Opdivo) for adjuvant melanoma.
        2019 ([cited 2019 September]; Available from)
        • NICE
        Dabrafenib with trametinib for adjuvant treatment of resected BRAF V600 mutation-positive melanoma.
        2018 ([cited 2019 September]; Available from:)
        • pCODR
        Final recommendation for dabrafenib (Tafinlar) combined with trametinib (Mekinist) for adjuvant melanoma.
        2019 ([cited 2019 September]; Available from:)
        • G-BA
        Anlage XII – Nutzenbewertung von Arzneimitteln mit neuen Wirkstoffen nach § 35a SGB V Pembrolizumab (neues Anwendungsgebiet: Melanom, adjuvante Therapie).
        2019 ([cited 2019 September]; Available from:)
        • G-BA
        Anlage XII – Beschlüsse über die Nutzenbewertung von Arzneimitteln mit neuen Wirkstoffen nach § 35a SGB V Nivolumab (neues Anwendungsgebiet: Melanom, adjuvante Behandlung).
        2019 ([cited 2019 September]; Available from:)
        • G-BA
        Mündliche Anhörung gemäß 5. Kapitel § 19 Abs. 2 Verfahrensordnung des Gemeinsamen Bundesausschusses, Nivolumab.
        2019 ([cited 2019 September]; Available from:)
        • G-BA
        Anlage XII – Beschlüsse über die Nutzenbewertung von Arzneimitteln mit neuen Wirkstoffen nach § 35a SGB V – dabrafenib (Melanom, in Kombination mit Trametinib, BRAF-V600-Mutation, adjuvante Behandlung).
        2019 ([cited 2019 September]; Available from:)
        • Molassiotis A.
        • Brunton L.
        • Hodgetts J.
        • Green A.C.
        • Beesley V.L.
        • Mulatero C.
        • et al.
        Prevalence and correlates of unmet supportive care needs in patients with resected invasive cutaneous melanoma.
        Ann Oncol. 2014; 25: 2052-2058
        • Sacristan J.A.
        • Aguaron A.
        • Avendano-Sola C.
        • Garrido P.
        • Carrion J.
        • Gutierrez A.
        • et al.
        Patient involvement in clinical research: why, when, and how.
        Patient Prefer Adherence. 2016; 10: 631-640
        • Mercieca-Bebber R.
        • King M.T.
        • Calvert M.J.
        • Stockler M.R.
        • Friedlander M.
        The importance of patient-reported outcomes in clinical trials and strategies for future optimization.
        Patient Relat Outcome Meas. 2018; 9: 353-367
        • Kersting C.
        • Kneer M.
        • Barzel A.
        Patient-relevant outcomes: what are we talking about? A scoping review to improve conceptual clarity.
        BMC Health Serv Res. 2020; 20: 596
        • van Leeuwen M.
        • Husson O.
        • Alberti P.
        • Arraras J.I.
        • Chinot O.L.
        • Costantini A.
        • et al.
        Understanding the quality of life (QOL) issues in survivors of cancer: towards the development of an EORTC QOL cancer survivorship questionnaire.
        Health Qual Life Outcome. 2018; 16: 114