Adjuvant treatment with anti-PD-1 in acral melanoma: A nationwide study
Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant an...
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| Published in | International journal of cancer Vol. 155; no. 8; pp. 1455 - 1465 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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15.10.2024
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| Abstract | Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti-PD-1 after complete resection. All stages III-IV AM and CM patients receiving adjuvant anti-PD-1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5-29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p = .002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HR
1.53; 95% CI: 1.07-2.17; p = .019). Two-year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p = .050). Two-year OS was significantly lower in AM (71.5% vs. 84.3%; p = .027). The results of this study suggest a poorer outcome of adjuvant-treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high-risk AM. |
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| AbstractList | Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti-PD-1 after complete resection. All stages III-IV AM and CM patients receiving adjuvant anti-PD-1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5-29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p = .002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HRadj 1.53; 95% CI: 1.07-2.17; p = .019). Two-year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p = .050). Two-year OS was significantly lower in AM (71.5% vs. 84.3%; p = .027). The results of this study suggest a poorer outcome of adjuvant-treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high-risk AM.Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti-PD-1 after complete resection. All stages III-IV AM and CM patients receiving adjuvant anti-PD-1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5-29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p = .002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HRadj 1.53; 95% CI: 1.07-2.17; p = .019). Two-year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p = .050). Two-year OS was significantly lower in AM (71.5% vs. 84.3%; p = .027). The results of this study suggest a poorer outcome of adjuvant-treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high-risk AM. Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti‐PD‐1 after complete resection. All stages III–IV AM and CM patients receiving adjuvant anti‐PD‐1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence‐free survival (RFS), distant metastasis‐free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5–29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM ( p = .002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HR adj 1.53; 95% CI: 1.07–2.17; p = .019). Two‐year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% ( p = .050). Two‐year OS was significantly lower in AM (71.5% vs. 84.3%; p = .027). The results of this study suggest a poorer outcome of adjuvant‐treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high‐risk AM. Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti-PD-1 after complete resection. All stages III-IV AM and CM patients receiving adjuvant anti-PD-1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5-29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p = .002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HR 1.53; 95% CI: 1.07-2.17; p = .019). Two-year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p = .050). Two-year OS was significantly lower in AM (71.5% vs. 84.3%; p = .027). The results of this study suggest a poorer outcome of adjuvant-treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high-risk AM. Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti‐PD‐1 after complete resection. All stages III–IV AM and CM patients receiving adjuvant anti‐PD‐1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence‐free survival (RFS), distant metastasis‐free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5–29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p = .002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HRadj 1.53; 95% CI: 1.07–2.17; p = .019). Two‐year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p = .050). Two‐year OS was significantly lower in AM (71.5% vs. 84.3%; p = .027). The results of this study suggest a poorer outcome of adjuvant‐treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high‐risk AM. |
| Author | Piersma, Djura de Groot, Jan-Willem B Bonenkamp, Johannes J van Rijn, Rozemarijn S van den Eertwegh, Alfons J M Bloem, Manja Hospers, Geke A P Vreugdenhil, Gerard Stevense-den Boer, Marion A M Suijkerbuijk, Karijn P M van den Berkmortel, Franchette W P J Boers-Sonderen, Marye J Haanen, John B de Meza, Melissa M van der Veldt, Astrid A M Aarts, Maureen J B Blokx, Willeke A M van Not, Olivier J Blank, Christian U Kapiteijn, Ellen W Wouters, Michel W J M |
| Author_xml | – sequence: 1 givenname: Manja orcidid: 0000-0001-9843-4285 surname: Bloem fullname: Bloem, Manja organization: Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands – sequence: 2 givenname: Olivier J orcidid: 0000-0002-3099-4873 surname: van Not fullname: van Not, Olivier J organization: Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands – sequence: 3 givenname: Maureen J B surname: Aarts fullname: Aarts, Maureen J B organization: Department of Medical Oncology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands – sequence: 4 givenname: Franchette W P J surname: van den Berkmortel fullname: van den Berkmortel, Franchette W P J organization: Department of Medical Oncology, Zuyderland Medical Centre Sittard, Sittard-Geleen, The Netherlands – sequence: 5 givenname: Christian U surname: Blank fullname: Blank, Christian U organization: Department of Medical Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands – sequence: 6 givenname: Willeke A M surname: Blokx fullname: Blokx, Willeke A M organization: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands – sequence: 7 givenname: Marye J surname: Boers-Sonderen fullname: Boers-Sonderen, Marye J organization: Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands – sequence: 8 givenname: Johannes J surname: Bonenkamp fullname: Bonenkamp, Johannes J organization: Department of Surgery, Radboud University Medical Centre, Nijmegen, The Netherlands – sequence: 9 givenname: Jan-Willem B surname: de Groot fullname: de Groot, Jan-Willem B organization: Isala Oncology Center, Zwolle, The Netherlands – sequence: 10 givenname: John B surname: Haanen fullname: Haanen, John B organization: Department of Medical Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands – sequence: 11 givenname: Geke A P surname: Hospers fullname: Hospers, Geke A P organization: Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands – sequence: 12 givenname: Ellen W surname: Kapiteijn fullname: Kapiteijn, Ellen W organization: Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands – sequence: 13 givenname: Melissa M orcidid: 0000-0003-1306-2713 surname: de Meza fullname: de Meza, Melissa M organization: Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands – sequence: 14 givenname: Djura surname: Piersma fullname: Piersma, Djura organization: Department of Internal Medicine, Medisch Spectrum Twente, Enschede, The Netherlands – sequence: 15 givenname: Rozemarijn S surname: van Rijn fullname: van Rijn, Rozemarijn S organization: Department of Internal Medicine, Medical Centre Leeuwarden, Leeuwarden, The Netherlands – sequence: 16 givenname: Marion A M surname: Stevense-den Boer fullname: Stevense-den Boer, Marion A M organization: Department of Internal Medicine, Amphia Hospital, Breda, The Netherlands – sequence: 17 givenname: Astrid A M surname: van der Veldt fullname: van der Veldt, Astrid A M organization: Department of Radiology and Nuclear Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands – sequence: 18 givenname: Gerard surname: Vreugdenhil fullname: Vreugdenhil, Gerard organization: Department of Internal Medicine, Maxima Medical Centre, Eindhoven, The Netherlands – sequence: 19 givenname: Alfons J M surname: van den Eertwegh fullname: van den Eertwegh, Alfons J M organization: Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands – sequence: 20 givenname: Karijn P M surname: Suijkerbuijk fullname: Suijkerbuijk, Karijn P M organization: Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands – sequence: 21 givenname: Michel W J M surname: Wouters fullname: Wouters, Michel W J M organization: Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands |
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| Cites_doi | 10.1016/j.ejca.2020.11.028 10.1016/j.tranon.2019.02.007 10.1016/0197‐2456(96)00075‐X 10.2340/actadv.v102.678 10.1158/1078‐0432.ccr‐22‐3145 10.1001/archdermatol.2008.609 10.1056/evidoa2200214 10.1136/jitc‐2020‐001642 10.1093/bjd/ljad183 10.1245/s10434‐013‐3089‐0 10.1186/s12967‐019‐2081‐2 10.1200/jco.2021.39.15_suppl.e21516 10.1016/j.ejca.2022.08.030 10.1016/j.annonc.2023.10.793 10.1001/jamaoncol.2023.1363 10.1016/j.ejca.2021.06.007 10.1177/1203475418800943 10.1016/j.ejca.2020.02.021 10.1016/j.cll.2011.03.005 10.1111/1346‐8138.15103 10.1016/S1470‐2045(15)70122‐1 10.1111/pcmr.12279 10.1056/nejmoa1802357 10.1016/j.clon.2021.09.006 10.1056/nejmoa2005493 10.1111/dth.15817 10.1016/j.ejca.2022.02.026 10.5858/arpa.2019‐0561‐RA 10.1016/j.ejca.2021.08.044 10.1038/s41591‐022‐01851‐x 10.1186/s12885‐016‐2747‐6 10.1016/j.ejca.2024.113563 10.3322/caac.21409 10.1158/1535‐7163.MCT‐17‐0386 10.1056/nejmoa1709030 10.3389/fonc.2020.524700 10.1038/nature22071 10.1016/j.ejca.2016.11.021 |
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| Keywords | melanoma acral melanoma immune checkpoint inhibitors adjuvant immunotherapy |
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| Snippet | Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to... |
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| SubjectTerms | Adjuvant therapy Adjuvants Adult Aged Aged, 80 and over Chemotherapy, Adjuvant - methods Clinical outcomes Female Humans Immune checkpoint inhibitors Immune Checkpoint Inhibitors - therapeutic use Male Melanoma Melanoma - drug therapy Melanoma - genetics Melanoma - mortality Melanoma - pathology Melanoma, Cutaneous Malignant Metastases Metastasis Middle Aged Mutation Netherlands - epidemiology Patients Programmed Cell Death 1 Receptor - antagonists & inhibitors Prospective Studies Registries Skin Neoplasms - drug therapy Skin Neoplasms - genetics Skin Neoplasms - mortality Skin Neoplasms - pathology Survival Survival analysis |
| Title | Adjuvant treatment with anti-PD-1 in acral melanoma: A nationwide study |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/38922879 https://www.proquest.com/docview/3093071380 https://www.proquest.com/docview/3072797777 |
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