Five-Year Outcomes With Nivolumab in Patients With Wild-Type BRAF Advanced Melanoma
Caroline Robert, Georgina V Long, Benjamin Brady, Caroline Dutriaux, Anna Maria Di Giacomo, Laurent Mortier, Piotr Rutkowski, Jessica C Hassel, Catriona M McNeil, Ewa Anna Kalinka, Céleste Lebbé, Julie Charles, Micaela M Hernberg, Kerry J Savage, Vanna Chiarion-Sileni, Catalin Mihalcioiu, Cornelia Mauch, Ana Arance, Francesco Cognetti, Lars Ny, Henrik Schmidt, Dirk Schadendorf, Helen Gogas, Jesús Zoco, Sandra Re, Paolo A Ascierto, Victoria Atkinson, Caroline Robert, Georgina V Long, Benjamin Brady, Caroline Dutriaux, Anna Maria Di Giacomo, Laurent Mortier, Piotr Rutkowski, Jessica C Hassel, Catriona M McNeil, Ewa Anna Kalinka, Céleste Lebbé, Julie Charles, Micaela M Hernberg, Kerry J Savage, Vanna Chiarion-Sileni, Catalin Mihalcioiu, Cornelia Mauch, Ana Arance, Francesco Cognetti, Lars Ny, Henrik Schmidt, Dirk Schadendorf, Helen Gogas, Jesús Zoco, Sandra Re, Paolo A Ascierto, Victoria Atkinson
Abstract
Purpose: The CheckMate 066 trial investigated nivolumab monotherapy as first-line treatment for patients with previously untreated BRAF wild-type advanced melanoma. Five-year results are presented herein.
Patients and methods: In this multicenter, double-blind, phase III study, 418 patients with previously untreated, unresectable, stage III/IV, wild-type BRAF melanoma were randomly assigned 1:1 to receive nivolumab 3 mg/kg every 2 weeks or dacarbazine 1,000 mg/m2 every 3 weeks. The primary end point was overall survival (OS), and secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.
Results: Patients were followed for a minimum of 60 months from the last patient randomly assigned (median follow-up, 32.0 months for nivolumab and 10.9 months for dacarbazine). Five-year OS rates were 39% with nivolumab and 17% with dacarbazine; PFS rates were 28% and 3%, respectively. Five-year OS was 38% in patients randomly assigned to dacarbazine who had subsequent therapy, including nivolumab (n = 37). ORR was 42% with nivolumab and 14% with dacarbazine; among patients alive at 5 years, ORR was 81% and 39%, respectively. Of 42 patients treated with nivolumab who had a complete response (20%), 88% (37 of 42) were alive as of the 5-year analysis. Among 75 nivolumab-treated patients alive and evaluable at the 5-year analysis, 83% had not received subsequent therapy; 23% were still on study treatment, and 60% were treatment free. Safety analyses were similar to the 3-year report.
Conclusion: Results from this 5-year analysis confirm the significant benefit of nivolumab over dacarbazine for all end points and add to the growing body of evidence supporting long-term survival with nivolumab mono-therapy. Survival is strongly associated with achieving a durable response, which can be maintained after treatment discontinuation, even without subsequent systemic therapies.
Trial registration: ClinicalTrials.gov NCT01721772.
Figures
References
- Bhatia S, Tykodi SS, Thompson JA: Treatment of metastatic melanoma: An overview. Oncology (Williston Park) 23:488-496, 2009
- Larkin J Chiarion-Sileni V Gonzalez R, et al. : Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 381:1535-1546, 2019
- Robert C Ribas A Schachter J, et al. : Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): Post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol 20:1239-1251, 2019
- Robert C Schachter J Long GV, et al. : Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372:2521-2532, 2015
- Larkin J Chiarion-Sileni V Gonzalez R, et al. : Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23-34, 2015
- Robert C Ribas A Hamid O, et al. : Durable complete response after discontinuation of pembrolizumab in patients with metastatic melanoma. J Clin Oncol 36:1668-1674, 2018
- Robert C Long GV Brady B, et al. : Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372:320-330, 2015
- Ascierto PA Long GV Robert C, et al. : Survival outcomes in patients with previously untreated BRAF wild-type advanced melanoma treated with nivolumab therapy: Three-year follow-up of a randomised phase 3 trial. JAMA Oncol 5:187-194, 2019
- Hirsch FR McElhinny A Stanforth D, et al. : PD-L1 immunohistochemistry assays for lung cancer: Results from phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project. J Thorac Oncol 12:208-222, 2017
- Hamid O Robert C Daud A, et al. : Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Ann Oncol 30:582-588, 2019
- Wolchok JD Chiarion-Sileni V Gonzalez R, et al. : Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 377:1345-1356, 2017
- Hodi FS Chiarion-Sileni V Gonzalez R, et al. : Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol 19:1480-1492, 2018
- Carlino MS Vanella V Girgis C, et al. : Cessation of targeted therapy after a complete response in BRAF-mutant advanced melanoma: A case series. Br J Cancer 115:1280-1284, 2016
- Baetz TD, Song X, Ernst DS, et al: A randomized phase III study of duration of anti-PD-1 therapy in metastatic melanoma (STOP-GAP): Canadian Clinical Trials Group study (CCTG) ME.13. J Clin Oncol 36, 2018 (suppl; abstr TPS9600)
- Schliep S Agaimy A Cavallaro A, et al. : Concealed complete response in melanoma patients under therapy with immune checkpoint inhibitors: Two case reports. J Immunother Cancer 6:2, 2018
- Tan AC Emmett L Lo S, et al. : FDG-PET response and outcome from anti-PD-1 therapy in metastatic melanoma. Ann Oncol 29:2115-2120, 2018
- Kong BY Menzies AM Saunders CA, et al. : Residual FDG-PET metabolic activity in metastatic melanoma patients with prolonged response to anti-PD-1 therapy. Pigment Cell Melanoma Res 29:572-577, 2016
- Huang AC Orlowski RJ Xu X, et al. : A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med 25:454-461, 2019
Source: PubMed