Nonprogression with Avelumab Treatment Associated with Gains in Quality of Life in Metastatic Merkel Cell Carcinoma

Kaufman, Howard L.; Hünger, Matthias; Hennessy, Meliessa; Schlichting, Michael; Bharmal, Murtuza

doi:10.2217/fon-2017-0470

Cited by 24 publications

(23 citation statements)

References 40 publications

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“…Several open-label phase II clinical trials involving anti-PD-1 or anti-PD-L1 antibodies have demonstrated durable responses to these agents in a subset of patients with MCC. In 88 patients with metastatic MCC who had previously received chemotherapy, treatment with the anti-PD-L1 antibody avelumab resulted in a 32.8% objective response rate (ORR), including complete — and durable — responses in 9.1% of patients 157 and an associated improvement in quality of life 158 . In a study involving 26 patients, treatment with the anti-PD-1 antibody pembrolizumab resulted in a 56% ORR, including complete responses in 15.4% of patients, as first-line systemic therapy 154 .…”

Section: Investigational Therapies In MCCmentioning

confidence: 99%

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities

et al. 2018

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Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer associated with advanced age and immunosuppression. Over the last decade, it has been discovered that MCC tumors are associated with either integrated Merkel cell polyomavirus, which likely drives tumorigenesis, or a high burden of UV-induced somatic mutations. Both virus-positive and virus-negative MCC tumors are immunogenic and PD-(L)1 checkpoint blockade has proven to be highly effective in treating most patients with metastatic MCC; however, about 50% of treated patients do not experience long term tumor control. Despite these rapid advances in the understanding and management of MCC, many basic, translational, and clinical research questions remain. In March 2018, an International Workshop on Merkel Cell Carcinoma Research was held at the National Cancer Institute where academic, government, and industry thought leaders met to identify high priority research questions. Here we review the biology and treatment of MCC and report the conclusions of the Workshop.

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Section: Investigational Therapies In MCCmentioning

confidence: 99%

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities

et al. 2018

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“…From (Table S5). Only one publication [40] re-validated the instrument in the study population and the psychometric results have been published elsewhere [42]. Overall, most of the publications reported differences between groups in terms of "clinically meaningful deterioration", "clinically meaningful improvement", "clinically relevant", "stable", "minimal change", "statistically significant", or "significant difference" (Table S5).…”

Section: Articles Reporting On Pro Resultsmentioning

confidence: 99%

“…For two of the latter, additional full-text manuscripts on PRO results alone were published. Thus, the 28 publications referred to 26 individual ICI-CTs on lung carcinoma ( n = 11) [ 14 – 24 ], melanoma ( n = 6) [ 25 – 30 ], renal cell carcinoma ( n = 3) [ 31 – 33 ], urothelial carcinoma ( n = 2) [ 34 , 35 ], Hodgkin’s lymphoma (n = 1) [ 36 , 37 ], head and neck carcinoma (n = 1) [ 38 , 39 ], Merkel cell carcinoma (n = 1) [ 40 ], and cervical and vaginal carcinoma (n = 1) [ 41 ] (Table S5 ). With regard to measured PRO concepts, all publications reported on health-related quality of life (HRQoL) or global health status (GHS) as assessed by the cancer-specific EORTC QLQ-C30 (17/26) and/or the generic EQ-5D (15/26).…”

Section: Resultsmentioning

confidence: 99%

“…In general, the selection of the PRO instrument(s) was justified based on previous use and validation in similar patient populations - either general cancer patients or disease-specific populations (Table S5 ). Only one publication [ 40 ] re-validated the instrument in the study population and the psychometric results have been published elsewhere [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

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Patient-reported outcome instruments used in immune-checkpoint inhibitor clinical trials in oncology: a systematic review

Colomer‐Lahiguera

Bryant‐Lukosius

Rietkoetter

et al. 2020

J Patient Rep Outcomes

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Context: Immune-checkpoint inhibitors (ICI) have shown significant benefits for overall survival across various cancer types. Patient-reported outcomes (PROs) are assessed in clinical trials as a measure of efficacy. However, it remains unclear to what extent current PRO instruments capture symptoms specific to ICI toxicities. We conducted a systematic review to identify the use and content validity of PRO instruments in ICI clinical trials in oncology. Methods: Literature was retrieved from PubMed, Embase, PsycINFO, Medline and CINAHL databases. Articles presenting ICI clinical trials' PRO results, clinical trial study protocols, and conference abstracts stating the use of PRO measures were assessed. We evaluated the validity of identified instruments by comparing their symptomrelated content with the adverse events reported in each ICI clinical trial. Results: From database inception until January 2020, we identified 191 ICI clinical trials stating the use of PRO measures of which 26 published PRO results. The cancer-specific EORTC QLQ-C30 and the generic EQ-5D questionnaires were the most widely used instruments, often in combination with disease-specific PROs. Instruments used to report PRO symptom-related toxicities covered 45% of the most frequently reported AEs, whereas 23% of AEs were partially covered and 29% were not covered at all. Of non-covered AEs, 59% referred to the dermatologic system. Partially covered AEs related to endocrine and specific types of pain. Conclusion: Despite the high frequency of symptom-related toxicities related to ICI, these events are only partially covered (or not addressed) by current PRO instruments, even when combined. Further research is needed to develop new strategies to tailor PRO instruments to specific ICI toxicities.

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“…20 Additionally, nonprogression of mMCC during treatment with avelumab has been shown to be associated with improvement in quality of life. 53 A similar cohort of patients with chemotherapy-refractory mMCC was treated with avelumab in a global expanded access program (NCT03089658). 54 The encouraging findings of JAVELIN Merkel 200 part A provided impetus and rationale to evaluate avelumab in the first-line setting in patients with mMCC.…”

Section: Javelin Merkel 200 Part Amentioning

confidence: 99%

Product review: avelumab, an anti-PD-L1 antibody

Collins

Gulley

2018

Human Vaccines & Immunotherapeutics

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Although immunotherapies have been employed for many decades, immune checkpoint inhibitors have only recently entered the oncologic landscape. Avelumab is a fully human monoclonal antibody that blocks the interaction between PD-L1 on tumor cells and PD-1 on T cells, thereby inhibiting immunosuppression in the tumor microenvironment and reducing tumor growth. Most early clinical trials of avelumab as monotherapy and in combination regimens were part of the international JAVELIN clinical trial program, which included more than 7000 patients in more than 30 trials with at least 15 tumor types. Avelumab has been approved by the U.S. FDA for the treatment of metastatic Merkel cell carcinoma and metastatic urothelial carcinoma that has progressed during or following treatment with a platinum-based regimen. Its acceptable safety profile and ability to induce durable responses in otherwise deadly tumors provide the rationale for its use in other tumor types and in combination with other therapies.

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Nonprogression with Avelumab Treatment Associated with Gains in Quality of Life in Metastatic Merkel Cell Carcinoma

Cited by 24 publications

References 40 publications

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities

Patient-reported outcome instruments used in immune-checkpoint inhibitor clinical trials in oncology: a systematic review

Product review: avelumab, an anti-PD-L1 antibody

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