Chemotherapy after immune checkpoint inhibitor failure in metastatic melanoma: a retrospective multicentre analysis

被引：41

作者：

Goldinger, Simone M. ^{[1
,2
]}

Buder-Bakhaya, Kristina ^{[3
,4
]}

Lo, Serigne N. ^{[2
]}

Forschner, Andrea ^{[5
]}

McKean, Meredith ^{[6
,7
]}

Zimmer, Lisa ^{[8
,9
]}

Khoo, Chloe ^{[10
]}

Dummer, Reinhard ^{[1
]}

Eroglu, Zeynep ^{[11
]}

Buchbinder, Elizabeth I. ^{[12
]}

Ascierto, Paolo A. ^{[13
]}

Gutzmer, Ralf ^{[14
]}

Rozeman, Elisa A. ^{[15
]}

Hoeller, Christoph ^{[16
]}

Johnson, Douglas B. ^{[17
]}

Gesierich, Anja ^{[18
]}

Koelblinger, Peter ^{[19
]}

Bennannoune, Naima ^{[20
,21
]}

Cohen, Justine, V ^{[22
]}

Kaehler, Katharina C. ^{[23
]}

Wilson, Melissa A. ^{[24
]}

Cebon, Jonathan ^{[25
]}

Atkinson, Victoria ^{[26
]}

Smith, Jessica L. ^{[27
]}

Michielin, Olivier ^{[28
]}

Long, Georgina, V ^{[2
,29
,30
,31
,32
]}

Hassel, Jessica C. ^{[3
,4
]}

Weide, Benjamin ^{[5
]}

Haydu, Lauren E. ^{[6
,7
]}

Schadendorf, Dirk ^{[8
,9
]}

McArthur, Grant ^{[10
]}

Ott, Patrick A. ^{[12
]}

Blank, Christian ^{[15
]}

Robert, Caroline ^{[20
,21
]}

Sullivan, Ryan ^{[22
]}

Hauschild, Axel ^{[23
]}

Carlino, Matteo S.

Garbe, Claus ^{[5
]}

Davies, Michael A. ^{[6
,7
]}

Menzies, Alexander M. ^{[2
,29
,30
,31
]}

机构：

[1] Univ Zurich, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland

[2] Univ Sydney, Melanoma Inst Australia, Poche Ctr, 40 Rocklands Rd, North Sydney, NSW 2060, Australia

[3] Univ Hosp Heidelberg, Dept Dermatol, Neuenheimer Feld 460, D-69120 Heidelberg, Germany

[4] Univ Hosp Heidelberg, Natl Ctr Canc NCT, Neuenheimer Feld 460, D-69120 Heidelberg, Germany

[5] Univ Tubingen, Dept Dermatol, Liebermeisterstr 25, D-72076 Tubingen, Germany

[6] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, 1400 Pressler St, Houston, TX 77006 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, 1400 Pressler St, Houston, TX 77006 USA

[8] Univ Hosp Essen, Dept Dermatol, Essen, Germany

[9] German Canc Consortium, Partner Site Essen, Essen, Germany

[10] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[11] H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, 12902 Magnolia Dr, Tampa, FL 33612 USA

[12] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA

[13] Ist Nazl Tumori IRCCS Fdn G Pascale, Dept Melanoma Canc Immunotherapy & Dev Therapeut, 1400 Pressler St, I-77006 Naples, Italy

[14] Ruhr Univ Bochum, Skin Canc Ctr, Dept Dermatol, Muhlenkreiskliniken, Campus Minden, Bochum, Germany

[15] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Med Oncol & Immunol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands

[16] Med Univ Vienna, Dept Dermatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria

[17] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[18] Univ Hosp Wuerzburg, Dept Dermatol, Wurzburg, Germany

[19] Paracelsus Med Univ, Dept Dermatol & Allergol, Salzburg, Austria

[20] Gustave Roussy, 114 Rue Edouard Vaillant, F-94805 Villejuef, France

[21] Paris Saclay Univ, 114 Rue Edouard Vaillant, F-94805 Villejuef, France

[22] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA

[23] Univ Hosp Schleswig Holstein UKSH, Dept Dermatol, Campus Kiel,Arnold Heller Str 3,Haus C, D-24105 Kiel, Germany

[24] NYU, Sch Med, NYU Langone Hlth, Perlmutter Canc Ctr, 160 E 34th St, New York, NY 10016 USA

[25] La Trobe Univ, Olivia Newton John Canc Res Inst, Sch Canc Med, Austin Hlth, 145 Studley Rd, Melbourne, Vic 3084, Australia

[26] Univ QLD, Princess Alexandra Hosp, Greenslopes Private Hosp, 199 Ipswich Rd, Woolloongabba, Qld 4102, Australia

[27] Crown Princess Mary Canc Ctr Westmead, Sydney, NSW, Australia

[28] Lausanne Univ Hosp, Precis Oncol Ctr, Dept Oncol, Rue Bugnon 21, CH-1011 Lausanne, Switzerland

[29] Royal North Shore Hosp, Reserve Rd, St Leonards, NSW 2065, Australia

[30] Mater Hosp, 25 Rocklands Rd, North Sydney, NSW 2060, Australia

[31] Univ Sydney, Fac Med & Hlth, Sydney, NSW, Australia

[32] Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia

来源：

EUROPEAN JOURNAL OF CANCER | 2022年 / 162卷

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

Immunotherapy; Checkpoint inhibitors; Chemotherapy; Anti-PD-1; antibodies; Cancer; Melanoma; PHASE-III TRIAL; BREAST-CANCER; DOUBLE-BLIND; STAGE-III; PACLITAXEL; DACARBAZINE; IPILIMUMAB; COMBINATION; SORAFENIB; NIVOLUMAB;

D O I：

10.1016/j.ejca.2021.11.022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Despite remarkably improved outcomes with immune checkpoint inhibition, many patients with metastatic melanoma will eventually require further therapy. Chemotherapy has limited activity when used first-line but can alter the tumour microenvironment and does improve efficacy when used in combination with immunotherapy in lung cancer. Whether chemotherapy after checkpoint inhibitor failure has relevant activity in patients with metastatic melanoma is unknown.Methods: Patients with metastatic melanoma treated with chemotherapy after progression on immunotherapy with checkpoint inhibitors were identified retrospectively from 24 melanoma centres. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety were examined.Results: In total, 463 patients were treated between 2007 and 2017. Fifty-six per cent had received PD-1-based therapy before chemotherapy. Chemotherapy regimens included carboplatin thorn paclitaxel (32%), dacarbazine (25%), temozolomide (15%), taxanes (9%, nabpaclitaxel 4%), fotemustine (6%) and others (13%). Median duration of therapy was 7.9 weeks (0-108). Responses included 0.4% complete response (CR), 12% partial response (PR), 21% stable disease (SD) and 67% progressive disease (PD). Median PFS was 2.6 months (2.2, 3.0), and median PFS in responders was 8.7 months (6.3, 16.3), respectively. Twelve-month PFS was 12% (95% CI 2-15%). In patients who had received anti-PD-1 before chemotherapy, the ORR was 11%, and median PFS was 2.5 months (2.1, 2.8). The highest activity was achieved with single-agent taxanes (N Z 40), with ORR 25% and median PFS 3.9 months (2.1, 6.2). Median OS from chemotherapy start was 7.1 months (6.5, 8.0). Subsequent treatment with checkpoint inhibitors achieved a response rate of 16% with a median PFS of 19.1 months (2.0-43.1 months). No unexpected toxicities were observed.Conclusion: Chemotherapy has a low response rate and short PFS in patients with metastatic melanoma who have failed checkpoint inhibitor therapy, although activity varied between reg-imens. Chemotherapy has a limited role in the management of metastatic melanoma. 2021 Elsevier Ltd. All rights reserved.

引用

页码：22 / 33

页数：12

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