Abstract
Renal cell carcinoma (RCC) management has seen a revolution over the last decades. Six Lebanese oncologists discussed recent updates in RCC management and outlined the challenges and future directions in Lebanon. Sunitinib continues to be a first-line choice for metastatic RCC in Lebanon, except for intermediate- and poor-risk patients. Immunotherapy is not always accessible to patients or selected routinely as first-line therapy. More data are needed on the sequencing of immunotherapy and tyrosine kinase inhibitor treatments and on the use of immunotherapy beyond progression and/or after failure of immunotherapy in the first-line setting. For second-line management, the clinical experience with axitinib for low tumor growth rate and nivolumab after progression on tyrosine kinase inhibitors make those two agents the most widely used. Several challenges affect the Lebanese practice, limiting the accessibility and availability of the medications. Reimbursement remains the most critical challenge, especially with the socioeconomic crisis of October 2019.
Tweetable abstract
Management of renal cell carcinoma in Lebanon
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. WHO International Agency for Research on Cancer. Global Cancer Observatory (2022). https://gco.iarc.fr
- 2. . Renal Cancer. StatPearls. StatPearls Publishing, FL, USA (2022). www.ncbi.nlm.nih.gov/books/NBK558975/
- 3. . Cancer statistics, 2021. CA Cancer J. Clin. 71(1), 7–33 (2021).
- 4. Cancer in Lebanon: a review of incidence rates from 2008 to 2015 and projections till 2025. South Asian J. Cancer 9(3), 147–152 (2020).
- 5. WHO International Agency for Research on Cancer. Lebanon (GLOBOCAN 2020) (2020). https://gco.iarc.fr/today/data/factsheets/populations/422-lebanon-fact-sheets.pdf
- 6. Cancer trends in Lebanon: a review of incidence rates for the period of 2003–2008 and projections until 2018. Popul. Health Metr. 12(1), 4 (2014).
- 7. . Kidney cancer in Lebanon: a specific histological distribution? Asian Pac. J. Cancer Prev. 16(1), 363–365 (2015).
- 8. . Role of targeted therapy in combination with surgery in renal cell carcinoma. Int. J. Urol. 23(1), 5–12 (2016).
- 9. . Financing the health system. Health Syst. Reform Lebanon (3), 29–54 (2003).
- 10. Financial burden of cancer drug treatment in Lebanon. Asian Pac. J. Cancer Prev. 17(7), 3173–3177 (2016).
- 11. Kidney cancer, version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J. Natl Compr. Canc. Netw. 20(1), 71–90 (2022). • The latest National Comprehensive Cancer Network (NCCN) focused guidelines for kidney cancer on the screening, diagnosis, staging, treatment and management of renal cell carcinoma (RCC).
- 12. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur. J. Cancer 49(6), 1287–1296 (2013).
- 13. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med. 356(2), 115–124 (2007).
- 14. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 14(13), 1287–1294 (2013).
- 15. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N. Engl. J. Med. 378(14), 1277–1290 (2018).
- 16. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N. Engl. J. Med. 356(22), 2271–2281 (2007).
- 17. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med. 380(12), 1116–1127 (2019).
- 18. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med. 380(12), 1103–1115 (2019).
- 19. . Cabozantinib exposure-response analysis for the phase 3 CheckMate 9ER trial of nivolumab plus cabozantinib versus sunitinib in first-line advanced renal cell carcinoma. Cancer Chemother. Pharmacol. 91(2), 179–189 (2023).
- 20. Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study. Lancet Oncol. 24(3), 228–238 (2023).
- 21. Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): progression-free survival by independent review and overall survival update. Eur. J. Cancer 94, 115–125 (2018).
- 22. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 30(5), 706–720 (2019). • The updated European Society for Medical Oncology (ESMO) clinical practice guidelines for the diagnosis, treatment and follow-up of RCC.
- 23. European Association of Urology guidelines on renal cell carcinoma: the 2022 update. Eur. Urol. 82(4), 399–410 (2022).
- 24. Discontinuing VEGF-targeted therapy for progression versus toxicity affects outcomes of second-line therapies in metastatic renal cell carcinoma. Clin. Genitourin. Cancer 15(3), 403–410.e402 (2017).
- 25. . Translating new data to the daily practice in second line treatment of renal cell carcinoma: the role of tumor growth rate. World J. Clin. Oncol. 8(2), 100–105 (2017).
- 26. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 17(7), 917–927 (2016). •• Randomized, open-label, phase III study comparing cabozantinib with everolimus in patients with RCC who had received previous treatment. Cabozantinib was superior to everolimus in the second-line setting, supporting its recommendation in US and European guidelines for second-line treatment of advanced RCC.
- 27. . Cabozantinib versus everolimus, nivolumab, axitinib, sorafenib and best supportive care: a network meta-analysis of progression-free survival and overall survival in second line treatment of advanced renal cell carcinoma. PLOS ONE 12(9), e0184423 (2017).
- 28. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378(9807), 1931–1939 (2011).
- 29. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med. 373(19), 1803–1813 (2015). •• Randomized, open-label, phase III study comparing nivolumab with everolimus in patients with RCC who had received previous treatment. Nivolumab was shown to be superior to everolimus, supporting its recommendation in both US and European guidelines for second-line treatment of advanced RCC.
- 30. . Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 17(1), e4–e5 (2016).
- 31. . Less is more? First impressions from COSMIC-313. Cancer Invest. 41(1), 101–106 (2023).
- 32. . Initial COSMIC-313 data show first-line triplet therapy prolongs PFS in advanced RCC with greater toxicity (16 September 2022). https://dailynews.ascopubs.org/do/initial-cosmic-313-data-show-first-line-triplet-therapy-prolongs-pfs-advanced-rcc
- 33. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N. Engl. J. Med. 379(5), 417–427 (2018).
- 34. Biomarker analysis from CheckMate 214: nivolumab plus ipilimumab versus sunitinib in renal cell carcinoma. J. Immunother. Cancer 10(3), e004316 (2022).
- 35. LBA5 – CheckMate 214: efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups. Ann. Oncol. 28, v621–v622 (2017).
- 36. IMmotion151: a randomized phase III study of atezolizumab plus bevacizumab vs sunitinib in untreated metastatic renal cell carcinoma (mRCC). J. Clin. Oncol. 36(Suppl. 6), 578–578 (2018).
- 37. . ESMO 2021: subsequent therapy following pembrolizumab + axitinib or sunitinib treatment for advanced RCC in the phase 3 KEYNOTE-426 study (2021). www.urotoday.com/conference-highlights/esmo-2021/esmo-2021-kidney-cancer/132229-esmo-2021-subsequent-therapy-following-pembrolizumab-axitinib-or-sunitinib-treatment-for-advanced-rcc-in-the-phase-3-keynote-426-study.html
- 38. Overall survival and independent review of response in CheckMate 214 with 42-month follow-up: first-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). J. Clin. Oncol. 38(Suppl. 6), 609–609 (2020).
- 39. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial. Lancet Oncol. 23(7), 888–898 (2022).
- 40. OSSMAR: an observational study to describe the use of sunitinib in real-life practice for the treatment of metastatic renal cell carcinoma. J. Glob. Oncol. 5, 1–10 (2019).
- 41. Real-world evidence data on metastatic renal-cell carcinoma treatment in Austria: the RELACS study. Clin. Genitourin. Cancer 17(5), e957–e967 (2019).
- 42. A population-based overview of sequences of targeted therapy in metastatic renal cell carcinoma. Clin. Genitourin. Cancer 12(4), e127–131 (2014).
- 43. Exposure-response modeling of cabozantinib in patients with renal cell carcinoma: implications for patient care. Cancer Treat. Rev. 89, 102062 (2020).
- 44. Comparison of efficacy and safety among axitinib, sunitinib, and sorafenib as neoadjuvant therapy for renal cell carcinoma: a retrospective study. Cancer Commun. (Lond.) 39(1), 56 (2019).
- 45. . Second-line treatment landscape for renal cell carcinoma: a comprehensive review. Oncologist 23(5), 540–555 (2018).
- 46. Lenvatinib in combination with everolimus in patients with advanced or metastatic renal cell carcinoma: a phase 1 study. Int. J. Urol. 25(11), 922–928 (2018).
- 47. . Indirect treatment comparisons including network meta-analysis: lenvatinib plus everolimus for the second-line treatment of advanced/metastatic renal cell carcinoma. PLOS ONE 14(3), e0212899 (2019).
- 48. Cabozantinib, a new standard of care for patients with advanced renal cell carcinoma and bone metastases? Subgroup analysis of the METEOR trial. J. Clin. Oncol. 36(8), 765–772 (2018).
- 49. . National Cancer Treatment Guidelines 2023 (April 16 2018). www.moph.gov.lb/en/Pages/9/1279/health-reform-in-lebanon
- 50. ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma. Ann. Oncol. 32(12), 1511–1519 (2021).
- 51. World Bank. The World Bank in Lebanon: overview. (2022). www.worldbank.org/en/country/lebanon/overview#1
- 52. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 21(12), 1563–1573 (2020).
- 53. . Sunitinib: ten years of successful clinical use and study in advanced renal cell carcinoma. Oncologist 22(1), 41–52 (2017).
- 54. . Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa. Nat. Rev. Clin. Oncol. 15(5), 310–324 (2018).