Adjuvant therapy versus watch-and-wait post surgery for stage III melanoma: a multicountry retrospective chart review

Aim: To describe treatment patterns among patients with stage III melanoma who underwent surgical excision in years 2011–2016, and assess outcomes among patients who subsequently received systemic adjuvant therapy versus watch-and-wait. Methods: Chart review of 380 patients from 17 melanoma centers in North America, South America and Europe. Results: Of 129 (34%) patients treated with adjuvant therapy, 85% received interferon α-2b and 56% discontinued treatment (mostly due to adverse events). Relapse-free survival was significantly longer for patients treated with adjuvant therapy versus watch-and-wait (hazard ratio = 0.63; p < 0.05). There was considerable heterogeneity in adjuvant treatment schedules and doses. Similar results were found in patients who received interferon-based adjuvant therapy. Conclusion: Adjuvant therapies with better safety/efficacy profiles will improve clinical outcomes in patients with stage III melanoma.

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Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial

The Lancet ◽

10.1016/s0140-6736(08)61033-8 ◽

2008 ◽

Vol 372 (9633) ◽

pp. 117-126 ◽

Cited By ~ 456

Author(s):

Alexander MM Eggermont ◽

Stefan Suciu ◽

Mario Santinami ◽

Alessandro Testori ◽

Wim HJ Kruit ◽

...

Keyword(s):

Adjuvant Therapy ◽

Pegylated Interferon ◽

Interferon Alfa ◽

Phase Iii ◽

Stage Iii ◽

Phase Iii Trial ◽

Pegylated Interferon Alfa ◽

Stage Iii Melanoma ◽

Resected Stage

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Evaluation of patients with surgically resected high-risk melanoma receiving adjuvant therapy in routine clinical practice in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9577 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9577-9577

Author(s):

Michael B. Atkins ◽

Cristina Julian ◽

Matthew H. Secrest ◽

Janet Lee ◽

Ana Maria Abajo Guijarro ◽

...

Keyword(s):

Adjuvant Therapy ◽

Checkpoint Inhibitors ◽

The United States ◽

Distant Recurrence ◽

Advanced Melanoma ◽

Stage Iii ◽

Braf Mutations ◽

Stage Iii Melanoma ◽

Resected Stage ◽

Braf Mutant

9577 Background: The management of patients with resected stage III melanoma has changed in recent years, and real-world data on recurrence patterns and adjuvant therapy responses are scarce. This study assessed adjuvant treatment patterns and outcomes in patients with advanced melanoma by BRAF status and relapse location. Methods: Patients diagnosed with stage III advanced melanoma between January 2011 and February 2020 in the nationwide Flatiron Health electronic health record–derived deidentified database were included if they were ≥18 years, received approved first-line (1L) adjuvant therapy after January 2018 with checkpoint inhibitors (CPIs; eg, nivolumab, pembrolizumab) or targeted therapies (TTs; eg, dabrafenib/trametinib), had 6 months’ follow-up and had ≥1 visit after starting adjuvant therapy (Cohort 1). Patients from Cohort 1 were included in Cohort 2 if they had a recurrence following initiation of adjuvant therapy, and those from Cohort 2 were included in Cohort 3 if they had a distant recurrence and available documented BRAF status at any time. Time to next systemic treatment (TTNT), overall survival (OS) and relapse free survival (RFS) were estimated using Kaplan-Meier (KM) methods from adjuvant therapy start (Cohort 1), first recurrence date (Cohort 2) or first distant recurrence date (Cohort 3). Results: Cohort 1 included 447 patients receiving 1L adjuvant therapy; Cohort 2 included patients after first distant (n = 47) or local (n = 35) relapse; Cohort 3 included distant-recurrent patients with tumors that were BRAF wild type (WT) (n = 22) or BRAF mutant (n = 23). The majority of patients were aged < 65 years. Across cohorts, relative use of TTs vs CPIs was similar: Cohort 1 (4.5% vs 96%), Cohort 2 (2.4% vs 98%) and Cohort 3 (2.2% vs 98%). Nivolumab was the most frequent treatment used across cohorts (84%-88%). In Cohort 1, 1- and 2-year KM probabilities for OS, RFS and TTNT were 93.5%/83.8%, 83.2%/70.6% and 84.0%/62.4%, respectively. In Cohort 2, for patients with local recurrence, 6- and 12-month OS probabilities were 93.4% and 78.8%, respectively, which were substantially higher than those for patients with distant recurrence (64.5% and 46.9%). In Cohort 3, for patients with documented BRAF mutations, 6- and 12-month OS rates from disease recurrence were 79.1% and 49.4%, respectively, which were greater than for those with BRAF-WT tumors (54.1% and 46.3%). Conclusions: Early RFS and OS outcomes for patients with surgically resected Stage III melanoma appear comparable to those reported in randomized clinical studies. The majority of patients with advanced melanoma, including patients who experienced recurrence, initiated treatment with CPIs. OS rates were numerically greater for Cohort 3 patients with BRAF-mutant tumors. Outcomes for patients with distant recurrence after adjuvant therapy remain unfavorable and represent a continued unmet medical need.

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ASO Author Reflections: Adjuvant Therapy for Stage III Melanoma With or Without Completion Lymph Node Dissection

Annals of Surgical Oncology ◽

10.1245/s10434-021-10838-w ◽

2021 ◽

Author(s):

Robert J. Torphy ◽

Martin D. McCarter ◽

Ana L. Gleisner

Keyword(s):

Lymph Node ◽

Adjuvant Therapy ◽

Lymph Node Dissection ◽

Stage Iii ◽

Completion Lymph Node Dissection ◽

Node Dissection ◽

Stage Iii Melanoma

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Recurrent disease in patients with stage III melanoma in the era of adjuvant immune and targeted therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21570 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21570-e21570

Author(s):

Victor Lo ◽

Valerie Francescutti ◽

Elaine McWhirter ◽

Forough Farrokhyar ◽

Linda May Lee

Keyword(s):

Targeted Therapy ◽

Adjuvant Therapy ◽

Median Time ◽

Adjuvant Treatment ◽

Systemic Therapy ◽

Recurrent Disease ◽

Stage Iii ◽

Recurrence Rates ◽

Time To Recurrence ◽

Stage Iii Melanoma

e21570 Background: Advancements in systemic therapy have reduced recurrence, and the adoption of nodal surveillance in place of dissection has reduced morbidity for patients with Stage III melanoma. The objective of this study was to describe the timing and pattern of recurrence in stage III melanoma patients and evaluate the impact of adjuvant treatment and nodal surveillance. Methods: A multicenter retrospective chart review of patients with pathologically confirmed Stage III cutaneous melanoma seen at either the Juravinski Cancer Centre or Walker Family Cancer Centre in Ontario, Canada from January 1, 2017 to December 31, 2019. Results: There were 137 patients with Stage III melanoma: 18% IIIA, 22% IIIB, 52% IIIC, and 8% Stage IIID as per the 8th American Joint Committee on Cancer (AJCC) 2018 staging system. 103 (75%) patients had sentinel lymph node biopsy (SLNB) only as part of initial surgical therapy, 6 (4%) had SLNB with completion dissection, and 25 (18%) had upfront radical nodal dissection. 67 (49%) patients received adjuvant therapy, of which 50 (74%) had immunotherapy, 17 (25%) received BRAF-targeted therapy, and 1 (1%) had interferon. 54 (39%) patients developed recurrent disease, with a median time to recurrence of 8.5 months (IQR: 4.3-14.9). The recurrence rates were 63% in patients who did not have adjuvant treatment and 37% in those who had adjuvant therapy, with a median time-to-recurrence of 7.5 and 9.0 months respectively. There were 30 (56%) loco-regional recurrences and 24 (44%) distant recurrences. Of the patients with loco-regional recurrence, 26 (87%) had SLNB only compared to 4 (13%) who had upfront or completion dissection. 12 (24%) patients recurred while on adjuvant treatment (7 distant recurrences and 5 loco-regional recurrences), and 8 (13%) patients recurred following completion of adjuvant treatment (5 distant recurrences and 3 loco-regional recurrences). Recurrences were detected by patients, clinicians, CT and nodal US surveillance in 43%, 20%, 28% and 9% of cases, respectively. The majority of loco-regional recurrence was detected clinically (67%) rather than by radiologic surveillance (33%). Of the 30 loco-regional recurrences, 24 underwent surgical resection of the recurrence, 4 had subsequent systemic therapy without surgery, 1 had intra-tumoral injections and 1 had no treatment. Conclusions: Recurrences in Stage III melanoma occur early, often within a year, with higher rates of loco-regional rather than distant disease. Recurrence rates were lower in those who received adjuvant therapy, but the majority of recurrences were detected by patients or clinicians, including loco-regional recurrences in patients who had SLNB only despite surveillance nodal US.

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Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial

Yearbook of Pediatrics ◽

10.1016/s0084-3954(09)79467-9 ◽

2010 ◽

Vol 2010 ◽

pp. 43-45

Author(s):

J.A. Stockman

Keyword(s):

Adjuvant Therapy ◽

Pegylated Interferon ◽

Interferon Alfa ◽

Phase Iii ◽

Stage Iii ◽

Phase Iii Trial ◽

Pegylated Interferon Alfa ◽

Stage Iii Melanoma ◽

Resected Stage

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Adjuvant therapy utilization among stage III melanoma patients.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e21574 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e21574-e21574

Author(s):

C. Lance Cowey ◽

Sameer R. Ghate ◽

Whitney C. Rhodes ◽

Thomas Wilson ◽

Briana Ndife ◽

...

Keyword(s):

Adjuvant Therapy ◽

Stage Iii ◽

Melanoma Patients ◽

Stage Iii Melanoma

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Pathological response and survival with neoadjuvant therapy in melanoma: A pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.9503 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 9503-9503 ◽

Cited By ~ 18

Author(s):

Alexander M. Menzies ◽

Elisa A. Rozeman ◽

Rodabe Navroze Amaria ◽

Alexander Chan Chi Huang ◽

Richard A. Scolyer ◽

...

Keyword(s):

Targeted Therapy ◽

Clinical Stage ◽

Complete Response ◽

Pooled Analysis ◽

Stage Iii ◽

Post Surgery ◽

Neoadjuvant Immunotherapy ◽

Neoadjuvant Systemic Therapy ◽

Melanoma Patients ◽

Stage Iii Melanoma

9503 Background: Pathological complete response (pCR) to neoadjuvant systemic therapy (NST) correlates with survival, and is recognized as a path to regulatory approval in several cancers. Recent trials have reported that neoadjuvant immunotherapy (IT) and targeted therapy (TT) regimens achieve high pCR rates and impressive recurrence-free survival in stage III melanoma, however, the relationship between pCR, relapse-free (RFS) and overall survival (OS) in larger datasets of melanoma patients (pts) remains unknown. Methods: We pooled data from 6 modern NST clinical trials of anti-PD-1 based immunotherapy or BRAF/MEK targeted therapy conducted across institutions participating in the INMC. Pts with RECIST measurable, surgically resectable clinical stage III melanoma who underwent surgery were included. NST regimens included nivolumab (as monotherapy or in combination with ipilimumab), pembrolizumab or dabrafenib+trametinib. Baseline disease characteristics, treatment regimen, pCR and RFS were examined. Results: 184 pts with clinical stage III melanoma (AJCCv7: 100 IIIB, 84 IIIC) completed NST (133 IT, 51 TT) and underwent surgery. Median age was 57y (range 18-87). A pCR was observed in 41% of patients; 51 (38%) with IT and 24 (47%) with TT. Median follow-up post-surgery is 13 mo (95% CI 12-16); 10 mo with IT and 22 mo with TT. 44 (24%) pts have recurred (17 loco-regional, 21 distant, 6 both sites at first recurrence), 18 (14%) after IT and 26 (51%) after TT. 12-month RFS was improved with IT vs TT (83% vs 65%, p < 0.001). For those with pCR, 7% have recurred, 0/51 (0%) after IT, 7/17 (41%) after TT. For those without pCR, 34% have recurred, 18/82 (22%) after IT and 19/27 (70%) after TT. 12-month RFS was improved in those with pCR vs without pCR (95% vs 62%, p < 0.001), including in those with IT (100% vs 72%, p < 0.001) and TT (88% vs 43%, p < 0.001). 16 (9%) patients have died including two who had a pCR, both from TT. Conclusions: Neoadjuvant IT and TT are active regimens in resectable clinical stage III melanoma patients and are associated with high pCR rate. The ability to achieve pCR correlates with improved RFS and remarkably no patient with pCR from immunotherapy has recurred to date.

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