Patient Experiences with Avelumab in Treatment-Naïve Metastatic Merkel Cell Carcinoma: Longitudinal Qualitative Interview Findings from JAVELIN Merkel 200, a Registrational Clinical Trial.

BACKGROUND AND OBJECTIVE: Avelumab is approved for the treatment of metastatic Merkel cell carcinoma, a rare aggressive skin cancer with a poor prognosis. The aim of this qualitative study embedded in a clinical trial was to explore patient experiences while receiving avelumab. METHODS: All treatment-naïve patients with metastatic Merkel cell carcinoma entering part B of the phase II, open-label, international, JAVELIN Merkel 200 trial (NCT02155647) were invited to participate in optional semi-structured phone interviews before avelumab administration (baseline) and at weeks 13 and 25. Interviews were conducted by trained professionals, audio-recorded, transcribed and analysed. Key concepts identified at baseline were assessed during follow-up interviews. RESULTS: Twenty-nine patients completed the baseline interview; 19 had at least one follow-up interview. Baseline interviews described the patients' challenging journeys before being correctly diagnosed with Merkel cell carcinoma, the negative psychological burden of living with a symptomless disease and the hope for avelumab to be a successful therapy. During the trial, most patients reported an increased or continued sense of hope and willingness to fight metastatic Merkel cell carcinoma. Patients who self-reported disease improvement (n = 12) also reported stability or improvement in physical well-being and ability to do daily activities, having more energy, worrying less and being optimistic. Six patients who reported their condition as stable (n = 4) or worsened (n = 3) reported a worsening of physical well-being. Nine patients reported fatigue/tiredness on the day of and after receiving avelumab. Baseline and longitudinal experiences were similar across countries. CONCLUSIONS: This study suggests that patients experience perceptible benefits in physical and psychological well-being following treatment success with first-line avelumab in metastatic Merkel cell carcinoma.

Update on the psychometric properties and minimal important difference (MID) thresholds of the FACT-M questionnaire for use in treatment-naïve and previously treated patients with metastatic Merkel cell carcinoma.

OBJECTIVES: For valid and reliable assessment of patients' Health-Related Quality of Life (HRQoL), it is crucial to use psychometrically robust instruments. In the context of rare diseases such as Merkel cell carcinoma (MCC), validated disease-specific instruments are often not available. The Functional Assessment of Cancer Therapy - Melanoma (FACT-M) was originally developed for use in melanoma. Its psychometric performance for use in MCC and minimal important difference (MID) thresholds have been previously reported based on a cohort of metastatic MCC patients who had disease progression following one or more prior line of chemotherapy (NCT02155647 Part A; n = 70). Since then, new data from the phase II JAVELIN Merkel 200 trial among treatment-naïve patients are available (NCT02155647 Part B; n = 102). This study aims to increase accuracy and precision of previously established psychometric properties and MID thresholds of FACT-M in metastatic MCC patients. METHODS: Published qualitative research suggests that patients with metastatic MCC had similar experiences and described similar concepts associated with their disease independent of whether they were treatment naïve or had prior treatment. Therefore, it was deemed appropriate to pool FACT-M data from Part A (previously treated) and Part B (treatment-naïve) cohorts for this study. Construct validity was assessed by evaluating item-factor correlations (convergent validity) and known-groups validity using ECOG performance status 0 versus 1. Concurrent validity was assessed using EQ-5D items. Internal consistency reliability was assessed using Cronbach's α. Anchor- and distribution-based approaches were used to derive MID thresholds. RESULTS: Overall, psychometric tests based on various validity (convergent, known-groups, concurrent) and reliability (Cronbach α) analyses confirmed previous findings in that FACT-M performs well in MCC patients. MID thresholds derived from this study are largely in line with previously established thresholds with some minor adjustments. CONCLUSIONS: In the context of rare diseases, which often have limited data available for psychometric testing, a reasonably large MCC patient sample was available for this study, enhancing accuracy and precision of previously established FACT-M psychometric properties and MID thresholds with only small deviations for use in metastatic MCC patients. Results suggest that the FACT-M is suitable for Merkel cell carcinoma regardless of patients' treatment status. TRIAL REGISTRATION: This study is a pre-planned post-hoc analysis conducted on data collected in Part A and Part B of the JAVELIN Merkel 200 trial. This trial was registered on 2 June 2014 with ClinicalTrials.gov as NCT02155647.

Living with Merkel Cell Carcinoma (MCC): Development of a Conceptual Model of MCC Based on Patient Experiences.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with limited treatment options at advanced stages. There is a paucity of data available regarding the impact of MCC and its management on patients' lives. This study aimed to address this gap by interviewing patients with metastatic MCC entering a trial of an immunotherapy (avelumab). METHODS: In a single-arm, open-label, international, phase 2 trial in patients with stage IV, chemotherapy-refractory, histologically confirmed MCC, patients were invited to participate in semi-structured phone interviews. These were conducted before avelumab administration. Interview transcripts were analysed qualitatively to identify concepts important to patients relating to their experience of metastatic MCC and its management. RESULTS: Nineteen patients were interviewed. Most reported MCC to be painless and asymptomatic. They reported being often misdiagnosed and described a long process before receiving the correct diagnosis. They also reported a feeling of "shock" after being informed of the severity and seriousness of their cancer. Overall, patients did not report impaired physical and cognitive capacities or impact on daily lives, either before or after diagnosis. However, patients and their relatives reported feelings of "worry" and "fear" about the unknown outcome of the disease. Chemotherapy and radiotherapy negatively affected patients physically and psychologically in their everyday lives. CONCLUSIONS: MCC disease was not perceived by the interviewed patients to result in severe functional limitations or to severely impact everyday activities, but was associated with substantial negative psychological impact. In contrast, chemotherapy and radiotherapy for MCC are highly debilitating and disrupt patients' lives. CLINICALTRIALS. GOV IDENTIFIER: NCT02155647.

Nonprogression with avelumab treatment associated with gains in quality of life in metastatic Merkel cell carcinoma.

AIM: To assess the association between tumor response and health-related quality of life (HRQoL) in patients with metastatic Merkel cell carcinoma treated with the anti-PD-L1 avelumab. MATERIALS & METHODS: Phase II single-arm trial (NCT02155647) data of 88 patients were analyzed. Correlations between percentage reduction in tumor size and change from baseline in Functional Assessment of Cancer Therapy - General (FACT-G), FACT - Melanoma (FACT-M) and EuroQol-5 Dimension scores were calculated. HRQoL and utility by tumor response (per the Response Evaluation Criteria In Solid Tumors version 1.1) was estimated. RESULTS: Tumor shrinkage correlated positively with patients' change from baseline in the FACT-M total (0.364 [95% CI: 0.050-0.607]) and subscale scores. Differences in HRQoL and utility between nonprogressive disease and progressive disease were clinically relevant. CONCLUSION: In patients with metastatic Merkel cell carcinoma, nonprogression during treatment with avelumab correlated with gains in HRQoL.

Psychometric properties of the FACT-M questionnaire in patients with Merkel cell carcinoma.

BACKGROUND: No validated disease-specific questionnaires exist to capture health-related quality of life (HRQoL) in patients with Merkel cell carcinoma (MCC). The Functional Assessment of Cancer Therapy - Melanoma (FACT-M) is validated in patients with melanoma, which shares many similarities with MCC. This paper reports the psychometric properties of the FACT-M in the metastatic MCC population. METHODS: Data were collected as part of a single-arm, open-label, multicenter trial involving patients with metastatic MCC who had failed at least one previous line of chemotherapy. FACT-M and EQ-5D were administered at baseline, Week 7, Week 13, and Week 25. An optional interview was administered at the same time points. MCC-specific FACT-M scores were derived following a combined quantitative and qualitative approach. Reliability and construct validity of original and additional MCC-specific FACT-M scores were assessed at baseline. Capacity to detect change in tumor size was assessed from baseline to Week 7. Minimally important differences (MIDs) were computed using distribution and anchor-based methods. RESULTS: Baseline assessments were available in 70 patients (mean age: 70 years; 74.3% male); 19 patients were interviewed at baseline. Additional MCC-specific scores were as follows: Physical Function score (six items), Psychological Impact score (six items), and MCC summary score (12 items). FACT-M original and additional MCC-specific scores both demonstrated acceptable psychometric properties: high reliability (Cronbach's alpha: 0.81-0.96), good convergent validity (correlations above 0.4 observed for 88% of items of the Melanoma surgery scale, 75% of items of the Melanoma scale, and 100% of items of the other FACT-M domains). Some evidence of floor/ceiling effects and poor discriminant ability was found. Higher scores (better HRQoL) on all FACT-M domains were observed in patients with better functioning (assessed by ECOG performance score), supporting clinical validity. Despite the small sample for responsiveness analysis (n = 37), the majority of FACT-M scores showed sensitivity to changes in tumor size at Week 7 with small to moderate effect sizes. MIDs were consistent with previously reported values in the literature for FACT-M domains. CONCLUSIONS: FACT-M is suitable to capture HRQoL in patients with metastatic MCC, thus making it a potential candidate for assessing HRQoL in MCC trials. TRIAL REGISTRATION: This study is a post-hoc analysis conducted on data collected in Part A of the JAVELIN Merkel 200 trial. This trial was registered on 2 June 2014 with ClinicalTrials.gov as NCT02155647 .

Quality of life outcomes after isolated limb infusion.

BACKGROUND: Isolated limb infusion (ILI) for the treatment of in-transit melanoma was originally described more than 10 years ago. Response rates of 45-53% have been reported in U.S. series. Long-term quality of life outcomes after this procedure have not been described. We hypothesized that ILI is rarely associated with long-term limb morbidity. METHODS: ILIs performed at our institution between July 2005 and June 2009 were reviewed. Patients were contacted cross-sectionally at 2 time points. During these interviews, response to treatment and postoperative limb function were assessed. RESULTS: Thirty-two ILIs were performed during the time period. Twenty-seven patients were treated for in-transit melanoma; 5 were treated for recurrent Merkel cell carcinoma. The 30-day mortality was 0%. Three patients (9%) required fasciotomy. Durable complete responses were achieved in 41% of patients, with mean follow-up time of 19.4 ± 9.6 months after infusion; after this period, 53% reported progression of disease. The most common postprocedure symptoms were edema (88%), numbness (59%), and pain (59%). By 3 months and at the time of last follow-up, the most common symptoms were edema (82%), numbness (65%), and stiffness (35%). No patients reported impaired limb function at the time of last follow-up compared to baseline. Median survival was 19.2 ± 4.2 months after infusion. CONCLUSIONS: ILI for melanoma and Merkel cell carcinoma is associated with postprocedure symptoms in most patients, most commonly edema, color change, and numbness. At last follow-up, no ILI patients had residual functional impairment in the treated limb.

Coping with cancer. A personal odyssey.

Building on personal experience, the psychological impact of cancer is reviewed. The subspecialty of psycho-oncology is a recent development within oncology, reflecting the increased interest in behavioral, psychological, and social factors in cancer prevention, treatment, and in improving the quality of life of patients with cancer at all stages through counseling and educational programs. Early identification of patients who are coping poorly is important for compliance with treatment and control of distress. It is equally important to recognize and diagnose common psychological disorders, primarily anxiety and depressive symptoms, which can occur. Referral for counseling to a mental health professional familiar with the care of patients with cancer may be indicated. My successful confrontation with cancer led to emotional growth. For those who cannot be sanguine about their experience, there may still be ways to reduce its, at times, devastating psychological impact. Hopefully, the days in which cancer patients had to suffer alone, in secrecy, and in fearful silence, are disappearing.