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Systemic therapy in malignant melanoma
This document summarizes systemic therapy options for malignant melanoma, including cytotoxics, immunotherapy, targeted therapies, and their outcomes. Key points discussed are: (1) Immunotherapy with checkpoint inhibitors like ipilimumab and pembrolizumab have significantly improved response rates and survival compared to traditional chemotherapies; (2) Combining BRAF and MEK inhibitors has become an important targeted therapy approach as it improves outcomes over BRAF inhibitors alone by delaying resistance; (3) Emerging evidence suggests combining immunotherapy and targeted therapies may provide further benefit.
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Systemic therapy in malignant melanoma
- 1. Systemic therapy inMalignant Melanoma Dr. Rajib Bhattacharjee DNB SS PDT (Medical Oncology)
- 2.
- 6. Systemic therapy inMalignant Melanoma Cytotoxics Immunotherapy BRAF inhibitors MEK inhibitors Miscellaneous Dacarbazine Temozolomide Nab Paclitaxel Fotemustine Pacli + Carbo Other combinations Dartmouth, CVD, etc Interleukin 2 Aldesleukin Checkpoint inh Ipilimumab Nivolumab Pembrolizumab Dabrafenib Vemurafenib Encorafenib Trametinib Cobimetinib Binimetinib IFN alfa T –VEC TIL – ACT KIT inhibitors Imatinib Dasatiib Sunitinib
- 8. Single Agent Cytotoxics •RR – 20% • S/E – Myelosuppression, NauseaDacarbazine • EORTC 18032 (TMZ v DTIC) • OSHR – 1.0, PFSHR – 0.92, RR – 14.4% v 9.8%Temozolomide • Nab Pacli v DTIC (No brain mets, LDH low) • PFS – 4.8 v 2.5 mo HR -0.792 • OS- 12.8 v 10.7 mo HR- 0.831 Nab Paclitaxel
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- 10. Adjuvant Systemic Therapy HDIFN alfa2b Peg IFN alfa Immunotherapy CTLA 4 inh PD 1 inh BRAF inh
- 13. Outcomes of IFNalfa 2b ECOG Trials – E1684, E1690, E1694, E2696 METAANALYSIS of 15 trials – improvement in OS & RFS
- 14. () EORTC 18991 (n= 1256) Peg IFN v Observation 7 Y RFS – 39% V 35% (HR – 0.87) OS – No difference (p = 0.57) (stage III N1 ulcerated OS HR – 0.59)
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- 17. EORTC 18071 -Results
- 20. Common side effectsof checkpoint inhibitors Fatigue Diarrhoea Itching Rash Nausea Vomiting Fatigue Lymphocytopenia Hyponatremia Shortness of breath Musculoskeletal pain Anorexia Cough Anemia, fatigue Hyperglycemia Hyponatremia Hypoalbuminemia Itching Cough Nausea
- 21. Immune mediated sideeffects of Checkpoint Inhibitors • Enterocolitis • Hepatitis • Dermatitis • Neuropathy • Endocrinoathy – Hypophysitis, Thyroiditis
- 24. 3 Y RFS– 58% v 39% 3 Y OS – 86% v 77%
- 25. Negative Trials •Vemurafenib v placebo •DFS– No Difference BRIM 8 •Nivo + Ipi v Nivo •RFS – No Difference CHECKMATE 915
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- 27. Systemic Agents inUnresectable or Metastatic Melanoma
- 28. IMMUNOTHERAPY High Dose Interleukine-2 Vaccines Checkpoint inhibitors • CTLA4 inhibitors • PD1 inhibitors Adoptive cell transfer therapy (ACT)
- 29. 1st cycle ALDESLEUKIN 6-7.2L U/Kg 8 hrly (till toxicity/ 15 doses) Gap of 10 days repeat if response/STABLE (assessed after 2 months) 2nd cycle ORR – 16 %
- 30. Vaccine • Heteroclitic gp100:209- 217 (210M) melanoma peptide vaccine • RR – 16% v 6% • OS – 18.0 v 11.1 mo
- 31. Checkpoint Inhibitors • IPILIMUMAB •PEMBROLIZUMAB • NIVOLUMAB
- 32. Hodi et al2010
- 33. Robert et al,2011
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- 50. BRAF & MEKinhibitors
- 51. Why using onlyBRAF inhibitor is counterproductive?
- 52. Resistance to BRAFinhibitor
- 58. OS – 22.3v 17.4 mo (HR – 0.7) Toxicities – 37% v 28%
- 62. Seems like bothBRAF inhibitor and immunotherapy works well.. How about using them together?
- 66. C-KIT Inhibitors Imatinib Dasatinib Sunitinib Actionable KITmutations L596 V559 K622E
- 68.
Editor's Notes
- #21 L pain