Efficacy comparison between anti-PD-1 antibody monotherapy and anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy for advanced acral melanoma: A retrospective, multicenter study of 254 Japanese patients

Nakamura, Yasuhiro; Namikawa, Kenjiro; Kiniwa, Yukiko; Katô, Hiroshi; Yoshikawa, Shusuke; Maekawa, Takeo; Matsushita, Satoru; Takenouchi, Tatsuya; Inozume, Takashi; Nakai, Yasuo; Fukushima, Satoshi; Saito, Shintaro; Otsuka, Atsushi; Fujimoto, Noriki; Isei, Taiki; Baba, Norihisa; Matsuya, Taisuke; Tanaka, Ryo; Kaneko, Takahide; Onishi, Masazumi; Kuwatsuka, Yutaka; Nagase, Kotaro; Onuma, T; Nomura, Motoo; Umeda, Yoshiyasu; Yamazaki, Naoya

doi:10.1016/j.ejca.2022.08.030

Cited by 17 publications

(42 citation statements)

References 39 publications

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“…Thereafter, 15 studies have reported the efficacy of anti-PD-1 monotherapy in treating AM. 39,41,[43][44][45][46][47][48][49][50][51][52][53][54][55][56] These studies had sample sizes of 7-209 patients and used different anti-PD-1 antibodies, including nivolumab, pembrolizumab, and toripalimab. The results of these studies, however, demonstrated contradicting findings: the ORRs ranged from 14%-40%; median PFS, 2.4-6.6 months; and median OS, 14.0-98.0 months.…”

Section: Anti-pd-1 Antibodymentioning

confidence: 99%

Immune checkpoint inhibitor‐based therapy for advanced acral and mucosal melanoma

Mori

Izumi

Doi

et al. 2022

Experimental Dermatology

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The advent of immune checkpoint inhibitors (ICIs) including anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) antibodies drastically changed treatment modalities for patients with various kinds of cancers, including lung cancer, 1 breast cancer, 2 oesophageal cancer, 3 urothelial cancer, 4 cervical cancer, 5 endometrial cancer, 6 renal cell carcinoma, 7,8 head and neck cancer, 9 Hodgkin lymphoma, 10 high microsatellite instability/ mismatch repair-deficient cancer, 11,12 tumour mutational burden (TMB)-high solid cancer, 13 and melanoma, 14,15 in advanced and/or adjuvant stage. ICIs are commonly used for treating advanced cutaneous melanoma (CM). In the phase III KEYNOTE-006 clinical trial, pembrolizumab resulted in an objective response rate (ORR) of 42% and a longer overall survival (OS) than ipilimumab (median OS: 32.7 months vs. 15.9 months; p < 0.001). 16 Likewise, the randomized phase III CheckMate-067 clinical trial demonstrated that nivolumab plus ipilimumab resulted in a better ORR and prolonged survival than nivolumab alone (ORR, 58% vs. 45%; median progression-free survival (PFS), 11.5 months vs. 6.9 months; median OS, not reached vs. 36.9 months). 17 Moreover, the 5-year OS has improved from <10% in patients with advanced stage CM treated with conventional chemotherapy, such as dacarbazine, to 30%-50%, especially in patients treated with anti-PD-1 antibody alone or in combination with ipilimumab. 16,18,19 CM is predominantly manifested in the sun-exposed skin of the Caucasian population. 20 However, melanomas rarely

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Section: Anti-pd-1 Antibodymentioning

confidence: 99%

Immune checkpoint inhibitor‐based therapy for advanced acral and mucosal melanoma

Mori

Izumi

Doi

et al. 2022

Experimental Dermatology

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“…Since the ORR to nivolumab plus ipilimumab combination therapy is higher than that for nivolumab monotherapy [57.6% (95% CI 52.0–63.2%) vs. 43.7% (95% CI 38.1–49.3%)] [ 1 ], this combination therapy is widely used for the treatment of advanced melanoma with or without BRAF mutations despite its high incidence of severe or serious adverse events (SAEs) [ 5 ]. Notably, in patients with acral melanoma (palm and sole melanoma) in the Japanese population, the efficacy of nivolumab plus ipilimumab combination therapy was not significantly better than that of anti-PD1 Ab monotherapy [ 19 ]. Indeed, the ORR was 31% ( p = 0.44), the PFS was 3.2 months ( p = 0.74) and the OS was not reached ( p = 0.55) in the nivolumab plus ipilimumab groups [ 19 ].…”

Section: Significance Of the Blockade Of Pd1/pd-l1 Pathways For The T...mentioning

confidence: 99%

“…Notably, in patients with acral melanoma (palm and sole melanoma) in the Japanese population, the efficacy of nivolumab plus ipilimumab combination therapy was not significantly better than that of anti-PD1 Ab monotherapy [ 19 ]. Indeed, the ORR was 31% ( p = 0.44), the PFS was 3.2 months ( p = 0.74) and the OS was not reached ( p = 0.55) in the nivolumab plus ipilimumab groups [ 19 ]. On the other hand, in non-acral melanoma in the Japanese population, the ORR to nivolumab plus ipilimumab was significantly higher than that of anti-PD1 Ab monotherapy (61% vs. 10%; p < 0.001) in the same retrospective study [ 19 ].…”

Section: Significance Of the Blockade Of Pd1/pd-l1 Pathways For The T...mentioning

confidence: 99%

“…Indeed, the ORR was 31% ( p = 0.44), the PFS was 3.2 months ( p = 0.74) and the OS was not reached ( p = 0.55) in the nivolumab plus ipilimumab groups [ 19 ]. On the other hand, in non-acral melanoma in the Japanese population, the ORR to nivolumab plus ipilimumab was significantly higher than that of anti-PD1 Ab monotherapy (61% vs. 10%; p < 0.001) in the same retrospective study [ 19 ]. Collectively, similar to anti-PD1 Abs [ 12 ], the efficacy of nivolumab plus ipilimumab combination therapy is determined, at least in part, by the clinical subtype of melanoma.…”

Section: Significance Of the Blockade Of Pd1/pd-l1 Pathways For The T...mentioning

confidence: 99%

“…Indeed, the ORR of anti-PD1 Abs is lower for unresectable acral melanoma (16.6%) [ 12 ] than for cutaneous melanoma (43.7%) [ 1 ], and the PFS and OS for the study cohort were 3.5 months and 18.2 months, respectively [ 12 ]. Moreover, another report suggested that, although Cox multivariate analysis suggested that performance states (PS) and elevated LDH is an independent predictor of a favorable OS and PS in the palm and sole melanoma, the efficacy of nivolumab plus ipilimumab combined therapy is not superior to that of anti-PD1 Abs for the treatment of advanced acral melanoma [ 19 ]. Surprisingly, this tendency is observed not only in the Asian population but also in other ethnic populations, including Hispanic and African patients with melanoma [ 45 ].…”

Section: Significance Of the Blockade Of Pd1/pd-l1 Pathways For The T...mentioning

confidence: 99%

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Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Fujimura

Muto

Asano

2022

IJMS

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Therapeutic options for treating advanced melanoma have progressed rapidly in recent decades. Until 6 years ago, the regimen for treating advanced melanoma consisted mainly of cytotoxic agents such as dacarbazine and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have been recognized as anchor drugs for treating advanced melanoma, with or without additional combination drugs such as ipilimumab, but the efficacies of these immunotherapies are not fully satisfactory. In this review, we describe the development of the currently available anti-PD1 Abs-based immunotherapies for advanced melanoma, focusing on their efficacy and immune-related adverse events (AEs), as well as clinical trials still ongoing for the future treatment of advanced melanoma.

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Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma

Mao

Lian

et al. 2023

JAMA Oncol

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ImportanceAcral melanoma, known for low tumor mutation burden, responds poorly to immunotherapy. A standard therapy is still lacking.ObjectiveTo investigate the activity and safety of camrelizumab (an anti–programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor 2 inhibitor) and temozolomide as first-line treatment in patients with advanced acral melanoma.Design, Setting, and ParticipantsIn this single-arm, single-center, phase 2 nonrandomized clinical trial, patients with treatment-naive unresectable stage III or IV acral melanoma were enrolled at Peking University Cancer Hospital and Institute between June 4, 2020, and August 24, 2021. The data cutoff date was April 10, 2022.InterventionsPatients received 4-week cycles of intravenous camrelizumab, 200 mg, every 2 weeks; oral apatinib 250 mg, once daily; and intravenous temozolomide, 200 mg/m2, once daily on days 1 to 5 until disease progression or unacceptable toxic effects.Main Outcomes and MeasuresThe primary end point was objective response rate as assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (version 1.1). Secondary end points included progression-free survival, time to response, duration of response, disease control rate, overall survival, and safety.ResultsA total of 50 patients (32 men [64%]; median age, 57 years [IQR, 52-62 years]) were enrolled and received treatment. The median follow-up duration was 13.4 months (IQR, 9.6-16.2 months). The objective response rate was 64.0% (32 of 50; 95% CI, 49.2%-77.1%). The median time to response and duration of response were 2.7 months (IQR, 0.9-2.9 months) and 17.5 months (95% CI, 12.0 to not reached), respectively. The disease control rate was 88.0% (44 of 50; 95% CI, 75.7%-95.5%). The estimated median progression-free survival was 18.4 months (95% CI, 10.6 to not reached). The median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse events were increased gamma-glutamyltransferase levels (15 [30%]), decreased neutrophil count (11 [22%]), increased conjugated bilirubin levels (10 [20%]), and increased aspartate aminotransferase levels (10 [20%]). No treatment-related deaths occurred.Conclusions and RelevanceThe findings of this nonrandomized clinical trial suggest that camrelizumab plus apatinib and temozolomide may be a potential first-line treatment option for patients with advanced acral melanoma, which warrants further validation in a randomized clinical trial.Trial RegistrationClinicalTrials.gov Identifier: NCT04397770

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Efficacy comparison between anti-PD-1 antibody monotherapy and anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy for advanced acral melanoma: A retrospective, multicenter study of 254 Japanese patients

Cited by 17 publications

References 39 publications

Immune checkpoint inhibitor‐based therapy for advanced acral and mucosal melanoma

Immune checkpoint inhibitor‐based therapy for advanced acral and mucosal melanoma

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma

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