Exploring supportive care and information needs through a proposed eHealth application among melanoma patients undergoing systemic therapy: a qualitative study.

BACKGROUND: During and after systemic therapy, patients with high risk and advanced melanoma experience challenges regarding cancer-related symptoms, treatment-related adverse events, and an impact of these symptoms on their physical and psychosocial well-being. Few studies have investigated the specific needs of these patients and the potential role of eHealth applications in meeting those needs. OBJECTIVE: To explore the supportive care and information needs of high risk and advanced melanoma patients, and how these needs can be supported by eHealth applications. METHODS: In this qualitative study, semi-structured interviews with high risk and advanced melanoma patients during or after systemic treatment were conducted to understand their needs and requirements as possible end-users of mobile eHealth applications. Interview transcripts were independently coded and thematically analyzed. RESULTS: Thirteen participants consented to be interviewed, aged 31 to 71 years. Nearly all patients (n = 12, 92%) experienced unmet information and supportive care needs during and after active treatment. Patients expected to value eHealth applications that facilitate information gathering, wellbeing interventions, and symptom management. The majority of patients (n = 10, 77%) anticipated various advantages from using an eHealth application, including increased autonomy, higher quality of life, and improved disease self-management. DISCUSSION: High risk and advanced melanoma patients have unmet supportive care and information needs during and after systemic treatment. The use of eHealth applications might be an effective way to meet these unmet needs. Patients anticipate a variety of advantages from using these applications, including deriving various benefits from the use of these applications, such as enhanced autonomy.

Phase Ib/II trial testing combined radiofrequency ablation and ipilimumab in uveal melanoma (SECIRA-UM).

Approximately, 50% of patients with uveal melanoma develop distant metastasis for which no standard therapy is established. In contrast to cutaneous melanoma, the anti-CTLA-4 antibody ipilimumab showed no clinical activity in uveal melanoma. Liver directed therapies improve local control, but fail to show overall survival (OS) benefit. Preclinical experiments demonstrated that radiofrequency ablation (RFA) induced durable responses in combination with anti-CTLA-4. The aim of this phase Ib/II study was to assess safety and efficacy of RFA plus ipilimumab in uveal melanoma. Patients underwent RFA of one liver lesion and subsequently received four courses ipilimumab 0.3, 3 or 10 mg/kg every 3 weeks in a 3 + 3 design. Primary endpoints were safety in terms of dose limiting toxicities per cohort to define the recommended phase II dose (RP2D) in the phase Ib part and confirmed the objective response rate and disease control rate (DCR) of non-RFA lesions in the phase II part. Secondary endpoints were progression-free survival (PFS) and OS. Ipilimumab 10 mg/kg + RFA was initially defined as the RP2D. However, after 19 patients, the study was amended to adjust the RP2D to ipilimumab 3 mg/kg + RFA, because 47% of patients treated with 10 mg/kg had developed grade 3 colitis. In the 3 mg/kg cohort, also 19 patients have been treated. Immunotherapy-related grade ≥3 adverse events were observed in 53% of patients in the 10 mg/kg cohort versus 32% in the 3 mg/kg cohort. No confirmed objective responses were observed; the confirmed DCR was 5% in the 10 mg/kg cohort and 11% in the 3 mg/kg cohort. Median PFS was 3 months and comparable for both cohorts, median OS was 14.2 months for the 10 mg/kg cohort versus 9.7 months for the 3 mg/kg cohort. Combining RFA with ipilimumab 3 mg/kg was well tolerated, but showed very limited clinical activity in uveal melanoma.

Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma.

Adjuvant ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) both improve relapse-free survival of stage III melanoma patients1,2. In stage IV disease, the combination of ipilimumab + nivolumab is superior to ipilimumab alone and also appears to be more effective than nivolumab monotherapy3. Preclinical work suggests that neoadjuvant application of checkpoint inhibitors may be superior to adjuvant therapy4. To address this question and to test feasibility, 20 patients with palpable stage III melanoma were 1:1 randomized to receive ipilimumab 3 mg kg-1 and nivolumab 1 mg kg-1, as either four courses after surgery (adjuvant arm) or two courses before surgery and two courses postsurgery (neoadjuvant arm). Neoadjuvant therapy was feasible, with all patients undergoing surgery at the preplanned time point. However in both arms, 9/10 patients experienced one or more grade 3/4 adverse events. Pathological responses were achieved in 7/9 (78%) patients treated in the neoadjuvant arm. None of these patients have relapsed so far (median follow-up, 25.6 months). We found that neoadjuvant ipilimumab + nivolumab expand more tumor-resident T cell clones than adjuvant application. While neoadjuvant therapy appears promising, with the current regimen it induced high toxicity rates; therefore, it needs further investigation to preserve efficacy but reduce toxicity.