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Clinical Studies

Failure to validate existing clinical prediction scale for response to PD-1 monotherapy in advanced melanoma in national cohort study

British Journal of Cancer volume 128, pages 707–710 (2023)Cite this article

Subjects

Treatment with targeted therapy and immune checkpoint inhibitors has significantly improved survival of patients with advanced melanoma. Unfortunately, a large proportion of patients are either primary non-responders or will eventually develop secondary resistance.

In 2017, Nosrati and colleagues published a prediction scale in the British Journal of Cancer, which included five clinical parameters that were associated with lower response to anti-PD-1 treatment; female sex (1 point), age <65 years (1 point), history of ipilimumab (anti-CTLA-4) treatment (2 points), elevated lactate dehydrogenase (LDH) (1 point), and the presence of liver metastasis (2 points) [1]. This study used a derivation cohort of 228 patients treated in California, and a validation cohort of 87 patients treated in Switzerland. The primary outcome measure was best tumour response to treatment evaluated using computed tomography at 12 and 16 weeks after the first administration of anti-PD-1 monotherapy, and every 12 weeks thereafter.

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Fig. 1: Receiver operation characteristics (ROC) curve of the clinical prediction scale of 0–7 points of Nosrati et al. to predict response to anti-PD-1 monotherapy in our cohort.

Data availability

Study protocol: available from MKvdK (e-mail, m.k.van_der_kooij@lumc.nl). Statistical code: not available. Data set: can be applied for at https://dica.nl/dmtr/onderzoek.

References

  1. Nosrati A, Tsai KK, Goldinger SM, Tumeh P, Grimes B, Loo K, et al. Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy. Br J Cancer. 2017;116:1141–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168:707–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Conforti F, Pala L, Bagnardi V, De Pas T, Martinetti M, Viale G, et al. Cancer immunotherapy efficacy and patients’ sex: a systematic review and meta-analysis. Lancet Oncol. 2018;19:737–46.

    Article  CAS  PubMed  Google Scholar 

  4. Wallis CJD, Butaney M, Satkunasivam R, Freedland SJ, Patel SP, Hamid O, et al. Association of patient sex with efficacy of immune checkpoint inhibitors and overall survival in advanced cancers: a systematic review and meta-analysis. JAMA Oncol. 2019;5:529–36.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sun L, Zhang L, Yu J, Zhang Y, Pang X, Ma C, et al. Clinical efficacy and safety of anti-PD-1/PD-L1 inhibitors for the treatment of advanced or metastatic cancer: a systematic review and meta-analysis. Sci Rep. 2020;10:2083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. van der Kooij MK, Dekkers OM, Aarts MJB, van den Berkmortel F, Boers-Sonderen MJ, de Groot JWB, et al. Sex-based differences in treatment with immune checkpoint inhibition and targeted therapy for advanced melanoma: a nationwide cohort study. Cancers. 2021;13:4639.

  7. Melief SM, Visconti VV, Visser M, van Diepen M, Kapiteijn EH, van den Berg JH, et al. Long-term survival and clinical benefit from adoptive T-cell transfer in stage IV melanoma patients is determined by a four-parameter tumor immune signature. Cancer Immunol Res. 2017;5:170–9.

    Article  CAS  PubMed  Google Scholar 

  8. Krieg C, Nowicka M, Guglietta S, Schindler S, Hartmann FJ, Weber LM, et al. High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy. Nat Med. 2018;24:144–53.

    Article  CAS  PubMed  Google Scholar 

  9. Diehl A, Yarchoan M, Hopkins A, Jaffee E, Grossman SA. Relationships between lymphocyte counts and treatment-related toxicities and clinical responses in patients with solid tumors treated with PD-1 checkpoint inhibitors. Oncotarget. 2017;8:114268–80.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Capone M, Giannarelli D, Mallardo D, Madonna G, Festino L, Grimaldi AM, et al. Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab. J Immunother Cancer. 2018;6:74.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Wagner NB, Forschner A, Leiter U, Garbe C, Eigentler TK. S100B and LDH as early prognostic markers for response and overall survival in melanoma patients treated with anti-PD-1 or combined anti-PD-1 plus anti-CTLA-4 antibodies. Br J Cancer. 2018;119:339–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This research received no external funding. The Netherlands Organization for Health Research and Development funded the start-up of the Dutch Melanoma Treatment Registry (DMTR). Grant number: 836002002. This grant was awarded under the effectiveness research for high-cost medicine programme. From its foundation, the DMTR has been sponsored by BMS, Novartis, Roche Nederland B.V., MSD, Pierre Fabre and the health insurance companies in the Netherlands via the Dutch Institute for Clinical Auditing (DICA). The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Authors and Affiliations

  1. Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, PO box 9600, 2300 RC, Leiden, The Netherlands

    Monique K. van der Kooij & Ellen Kapiteijn

  2. Department of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3000 CA, Rotterdam, The Netherlands

    Arjen Joosse & Astrid A. M. van der Veldt

  3. Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Karijn P. M. Suijkerbuijk

  4. Department of Medical Oncology, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands

    Maureen J. B. Aarts

  5. Department of Medical Oncology, Zuyderland Medical Center, 6130 MB, Sittard-Geleen, The Netherlands

    Franchette W. P. J. van den Berkmortel

  6. Department of Medical Oncology, Netherlands Cancer Institute- Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Christian U. Blank & John B. A. G. Haanen

  7. Department of Medical Oncology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500 HB, Nijmegen, The Netherlands

    Marye J. Boers-Sonderen

  8. Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1117, 1081 HZ, Amsterdam, The Netherlands

    Alfonsus J. M. van den Eertwegh

  9. Isala Oncology Center, Isala, 8000 GK, Zwolle, The Netherlands

    Jan Willem B. de Groot

  10. Department of Medical Oncology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Geke A. P. Hospers

  11. Department of Medical Oncology, Medisch Spectrum Twente, Koningsplein 1, 7512 KZ, Enschede, The Netherlands

    Djura Piersma

  12. Department of Medical Oncology, Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, The Netherlands

    Rozemarijn S. van Rijn

  13. Department of Medical Oncology, Maxima Medical Center, de Run 4600, 5500 MB, Veldhoven, The Netherlands

    Gerard Vreugdenhil

  14. Department of Medical Oncology, Amphia Ziekenhuis, Langendijk 175, 4819 EV, Breda, The Netherlands

    Hans M. Westgeest

  15. Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, 2333 AA, Leiden, The Netherlands

    Michel W. J. M. Wouters

  16. Department of Surgical Oncology, Netherlands Cancer Institute- Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Michel W. J. M. Wouters

  17. Department of Clinical Epidemiology, Leiden University Medical Center, Albinusdreef 2, PO box 9600, 2300 RC, Leiden, The Netherlands

    Olaf M. Dekkers

Authors
  1. Monique K. van der Kooij
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  2. Arjen Joosse
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  6. Christian U. Blank
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  7. Marye J. Boers-Sonderen
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  11. Geke A. P. Hospers
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  13. Rozemarijn S. van Rijn
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  14. Astrid A. M. van der Veldt
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  17. Michel W. J. M. Wouters
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  18. Olaf M. Dekkers
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  19. Ellen Kapiteijn
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Contributions

Conceptualisation, MKvdK, OMD and EK; data curation, MKvdK; formal analysis, MKvdK; methodology, MKvdK, OMD and EK; resources, FWPJvdB, MJB-S, JWBdG, GAPH, DP, RSvR, KPMS, HMW, AAMvdV, GV, CUB, MWJMW, JBAGH, AJMvdE and EK; software, MJBA; supervision, OMD and EK; visualisation, MKvdK; writing—original draft, MKvdK; writing—review and editing, OMD, MJBA, FWPJvdB, MJB-S, JWBdG, GAPH, DP, RSvR, KPMS, HMW, AAMvdV, GV, CUB, MWJMW, JBAGH, AJMvdE and EK. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Ellen Kapiteijn.

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Competing interests

MJBS has served as an advisory board member for Bristol-Myers Squibb, Novartis, Merck and Pierre Fabre. AJMvdE has served as a speaker for Bristol-Myers Squibb and Novartis and an advisory board member for Bristol Myers Squibb, MSD oncology, Amgen, Roche, Novartis, Sanofi, Pfizer, Ipsen, Merck, Pierre Fabre and has received research grants not related to this paper from Sanofi, Roche, Bristol Myers Squibb, TEVA and Idera. CUB has served as ab advisory board member for Bristol-Myers Squibb, MSD, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, GenMab, and Pierre Fabre, and reports to have ownership interests in Uniti Cars, Neon Therapeutics, and Forty Seven, and received commercial grants from Novartis, Bristol-Myers Squibb, and NanoString. JWBdG is a paid consultant for Bristol Myers Squibb, MSD, Pierre Fabre, and Servier. GAPH is an unpaid consultant/advisory board member for Bristol Myers Squibb, MSD, Roche, and Novartis. DP has served as an advisory board member for Amgen, Bristol Myers Squibb and Pierre Fabre. AAMvdV is a paid consultant for Bristol Myers Squibb, MSD, Novartis, Roche, Pfizer, Eisai, Ipsen, Pierre Fabre, Sanofi, and Bayer. JH is a paid consultant for AIMM, Neon Therapeutics, Immunocore, Vaximm, and Neogene Therapeutics, and reports receiving commercial research grants from Bristol Myers Squibb, MSD, Novartis, and Neon Therapeutics. KPMS has served as a consultant and/or advisory board member for Bristol Myers Squibb, Novartis, MSD, Pierre Fabre and AbbVie and received honoraria/research support not related to this manuscript from Novartis, Roche and MSD. All paid to institution. EK has served as a consultant and/or advisory board member for Bristol Myers Squibb, Novartis, Merck, Pierre Fabre and has received research grants not related to this paper from Bristol Myers Squibb. HMW received travel expenses from Ipsen and honoraria from Astellas and Roche. No potential conflicts of interest were disclosed by the other authors. Role of the funder: the funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Ethics approval and consent to participate

The DMTR was approved by a medical ethical committee (METC Leiden University Medical Center, 2013) and is not considered subject to the Medical Research Involving Human Subjects Act. Patient consent was waived due to the fact that the DMTR was not considered to be subject to the Medical Research Involving Human Subjects Act.

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van der Kooij, M.K., Joosse, A., Suijkerbuijk, K.P.M. et al. Failure to validate existing clinical prediction scale for response to PD-1 monotherapy in advanced melanoma in national cohort study. Br J Cancer 128, 707–710 (2023). https://doi.org/10.1038/s41416-022-02088-8

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  • DOI: https://doi.org/10.1038/s41416-022-02088-8

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