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Immune-checkpoint inhibitors in melanoma and kidney cancer: from sequencing to rational selection

Michael Flynn1, Lisa Pickering1, James Larkin1

  • 1Royal Marsden Hospital, London, UK.

Therapeutic Advances in Medical Oncology
|July 7, 2018
PubMed

Insights

Immune-checkpoint inhibitors (ICPIs) show promise in advanced melanoma and renal cell carcinoma. Further research is needed to improve patient selection and overcome resistance for better survival outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Immune-checkpoint inhibitors (ICPIs) targeting CTLA-4 and PD-1 offer durable responses in advanced melanoma and renal cell carcinoma.
  • Despite advances, survival in the metastatic setting remains poor, highlighting the need for improved therapeutic strategies.

Purpose of the Study:

  • To discuss current and emerging therapeutic approaches in advanced melanoma and renal cell carcinoma.
  • To explore strategies for enhancing patient selection and overcoming ICPI resistance.
  • To review combination therapies and treatment sequencing for improved efficacy.

Main Methods:

  • Review of current literature on ICPIs, targeted agents, and combination therapies.
  • Discussion of biomarker development for predicting ICPI responsiveness and resistance.
  • Analysis of adaptive, biomarker-driven clinical trial designs.

Main Results:

  • ICPIs have demonstrated efficacy in first-line and refractory settings for melanoma and renal cell carcinoma.
  • Targeted therapies and ICPIs show potential in the adjuvant setting for melanoma, and targeted therapies for renal cell carcinoma.
  • Combination strategies aim to circumvent ICPI resistance and enhance overall efficacy.

Conclusions:

  • Improved predictive biomarkers and resistance mechanisms identification are crucial for optimizing patient selection.
  • Adaptive, biomarker-driven trials are essential for advancing ICPI-based therapies.
  • Refined treatment sequencing and combination approaches are necessary to improve survival in metastatic settings.
Keywords:
biomarkersimmune-checkpoint inhibitorsmelanomarenal cell carcinomaresistancesequencingtargeted therapies

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