Long-term follow-up results from KEYNOTE-041: Phase 1b study of pembrolizumab in Japanese patients with advanced melanoma.
Japanese
advanced melanoma
long‐term follow‐up
pembrolizumab
subtype
Journal
The Journal of dermatology
ISSN: 1346-8138
Titre abrégé: J Dermatol
Pays: England
ID NLM: 7600545
Informations de publication
Date de publication:
26 Mar 2024
26 Mar 2024
Historique:
revised:
27
09
2023
received:
27
06
2023
accepted:
28
09
2023
medline:
26
3
2024
pubmed:
26
3
2024
entrez:
26
3
2024
Statut:
aheadofprint
Résumé
Pembrolizumab demonstrated an acceptable safety profile and promising antitumor activity in Japanese patients with advanced melanoma in the phase 1b KEYNOTE-041 (Study of Pembrolizumab [MK-3475] in Participants With Advanced Melanoma) trial. To evaluate the long-term efficacy and safety of pembrolizumab in Japanese patients with advanced melanoma in KEYNOTE-041. The current analysis reports results of additional follow-up of approximately 12 months since the initial analysis. Eligible patients had locally advanced (unresectable stage III) or metastatic (stage IV) melanoma not amenable to local therapy and had received two or fewer prior systemic therapies. Pembrolizumab 2 mg/kg was given every 3 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points included safety, tolerability, and overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by independent central review. The data cutoff for this analysis was August 30, 2017. Forty-two patients were followed up for a median of 22.3 months (range, 2.63-30.82 months). The ORR was 24.3% (nine of 37 evaluable patients [95% confidence interval (CI), 11.8%-41.2%]). Two patients with partial response at the time of the initial analysis achieved complete response. The median overall survival (OS) was 25.1 months (95% CI, 13.1-not reached] and the 30-month OS rate was 46.3% (95% CI, 29.8%-61.3%). The median duration of response was not reached. Treatment-related adverse events (TRAEs) were reported in 78.6% of patients; the incidence of grade 3 to 5 TRAEs was 23.8%. No additional treatment-related deaths occurred since the initial analysis. Pembrolizumab provided durable antitumor activity and an acceptable safety profile in Japanese patients with advanced melanoma.
Identifiants
pubmed: 38529706
doi: 10.1111/1346-8138.17002
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : MSD K.K.
Informations de copyright
© 2024 MSD K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.
Références
Herrscher H, Robert C. Immune checkpoint inhibitors in melanoma in the metastatic, neoadjuvant, and adjuvant setting. Curr Opin Oncol. 2020;32:106–113.
Kandolf Sekulovic L, Guo J, Agarwala S, Hauschild A, McArtur G, Cinat G, et al. Access to innovative medicines for metastatic melanoma worldwide: melanoma World Society and European Association of Dermato‐oncology survey in 34 countries. Eur J Can. 2018;104:201–209.
Namikawa K, Yamazaki N. Targeted therapy and immunotherapy for melanoma in Japan. Curr Treat Options Oncol. 2019;20:7.
KEYTRUDA®. (Pembrolizumab) injection, for intravenous use. 08/2021. Merck Sharp & Dohme LLC: Rahway, NJ, USA. 2021.
Hamid O, Puzanov I, Dummer R, Schachter J, Daud A, Schadendorf D, et al. Final analysis of a randomized trial comparing pembrolizumab versus investigator‐choice chemotherapy for ipilimumab‐refractory advanced melanoma. Eur J Can. 2017;86:37–45.
Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. Five‐year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE‐001. Ann Oncol. 2019;30:582–588.
Robert C, Ribas A, Schachter J, Arance A, Grob JJ, Mortier L, 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. 2019;20:1239–1251.
Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA. 2016;315:1600–1609.
Yamazaki N, Takenouchi T, Fujimoto M, Ihn H, Uchi H, Inozume T, et al. Phase 1b study of pembrolizumab (MK‐3475; anti‐PD‐1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE‐041). Cancer Chemother Pharmacol. 2017;79:651–660.
Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. Safety and tumor responses with lambrolizumab (anti‐PD‐1) in melanoma. N Engl J Med. 2013;369:134–144.
Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator‐choice chemotherapy for ipilimumab‐refractory melanoma (KEYNOTE‐002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16:908–918.
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–2532.
Hodi FS, Chiarion‐Sileni V, Gonzalez R, Glob JJ, Rutkowski P, Cowey CL, 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. 2018;19:1480–1492.
Ascierto PA, Long GV, Robert C, Brady B, Dutriaux C, Di Giacomo AM, et al. Survival outcomes in patients with previously untreated BRAF wild‐type advanced melanoma treated with nivolumab therapy: three‐year follow‐up of a randomized phase 3 trial. JAMA Oncol. 2019;5:187–194.
Yamazaki N, Kiyohara Y, Uhara H, Uehara J, Fujisawa Y, Takenouchi T, et al. Long‐term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma. Cancer Sci. 2019;110:1995–2003.
Uhara H, Kiyohara Y, Uehara J, Fujisawa Y, Takenouchi T, Otsuka M, et al. Five‐year survival with nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma. J Dermatol. 2021;48:592–599.
Takahashi A, Namikawa K, Ogata D, Nakano E, Jinnai S, Nakama K, et al. Real‐world efficacy and safety data of nivolumab and ipilimumab combination therapy in Japanese patients with advanced melanoma. J Dermatol. 2020;47:1267–1275.
Takahashi A, Namikawa K, Ogata D, Jinnai S, Nakano E, Yamazaki N. Updated analysis of nivolumab and ipilimumab combination therapy in Japanese patients with advanced melanoma. J Dermatol. 2023;50:525–535.
Fujisawa Y, Yoshikawa S, Minagawa A, Takenouchi T, Yokota K, Uchi H, et al. Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma. Cancer Med. 2019;8:2146–2156.
Fujisawa Y, Yoshikawa S, Minagawa A, Takenouchi T, Yokota K, Uchi H, et al. Classification of 3097 patients from the Japanese melanoma study database using the American joint committee on cancer eighth edition cancer staging system. J Dermatol Sci. 2019;94:284–289.
Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353:2135–2147.
Sakaizawa K, Ashida A, Uchiyama A, Ito T, Fujisawa Y, Ogata D, et al. Clinical characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients. J Dermatol Sci. 2015;80:33–37.
Puzanov I, Ribas A, Robert C, Schachter J, Nyakas M, Daud A, et al. Association of BRAF V600E/K mutation status and prior BRAF/MEK inhibition with pembrolizumab outcomes in advanced melanoma: pooled analysis of 3 clinical trials. JAMA Oncol. 2020;6:1256–1264.
Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD‐1 inhibition. N Engl J Med. 2017;377:2500–2501.
Furney SJ, Turajlic S, Stamp G, Thomas JM, Hayes A, Strauss D, et al. The mutational burden of acral melanoma revealed by whole‐genome sequencing and comparative analysis. Pigment Cell Melanoma Res. 2014;27:835–838.
Wolchok JD, Chiarion‐Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, et al. Five‐year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381:1535–1546.
Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open‐label phase 3 study (KEYNOTE‐006). Lancet. 2017;390:1853–1862.