Nüks Lgsoc’ta Sistemik Tedavi Yaklaşımı: Endokrin Tedavi, Hedefe Yönelik Tedaviler ve Kemoterapiye Rasyonel Sınırlar
Özet
Düşük dereceli seröz over karsinomu (LGSOC), indolen seyirli olmakla birlikte tekrarlama eğilimi belirgin ve uzun süreli sistemik tedavi gereksinimi doğuran özgün bir epitelyal over kanseri alt tipidir. Nüks hastalıkta standart sitotoksik kemoterapiye yanıtın sınırlı olması, tedavi stratejisinin hastalık temposu, semptom yükü, önceki tedaviler ve moleküler özellikler (özellikle MAPK yolak aktivasyonu) doğrultusunda bireyselleştirilmesini zorunlu kılar. Endokrin tedavi, düşük toksisite profili ve sürdürülebilir hastalık kontrolü potansiyeli nedeniyle çoğu olguda temel yaklaşım olarak konumlanır. MEK inhibitörleriyle hedefe yönelik tedaviler, randomize verilerle progresyonsuz sağkalımı uzatan seçenekler sunar; yeni nesil kombinasyon stratejileri belirli moleküler alt gruplarda umut vericidir. Kemoterapi ve/veya anti-VEGF yaklaşımlar ise hızlı progresyon, yüksek tümör yükü veya belirgin semptom varlığında amaç odaklı ve erken yeniden değerlendirme ilkesiyle, seçilmiş olgularda kullanılmalıdır.
Low-grade serous ovarian carcinoma (LGSOC) is a distinct epithelial ovarian cancer subtype characterized by an indolent course, frequent recurrences, and a prolonged need for systemic therapy. In the recurrent setting, limited responsiveness to conventional cytotoxic chemotherapy mandates a tailored strategy guided by disease tempo, symptom burden, prior treatments, and tumor biology, particularly MAPK pathway alterations. Endocrine therapy commonly serves as a backbone because of its favorable tolerability and capacity to achieve durable disease control in selected patients. Targeted therapies, most notably MEK inhibition, have demonstrated clinically meaningful improvements in progression-free survival in randomized data, supporting their central role in treatment sequencing. Emerging combination approaches that intensify MAPK suppression or leverage complementary pathways may further expand options for molecularly defined subgroups. By contrast, chemotherapy and/or anti-VEGF strategies should be reserved for clearly defined scenarios such as rapid progression, high-volume symptomatic disease, or urgent need for tumor debulking, and should be implemented with explicit goals and early response reassessment.
Referanslar
Kelliher L, Yoeli-Bik R, Schweizer L, Lengyel E. Molecular changes driving low-grade serous ovarian cancer and implications for treatment. Int J Gynecol Cancer. 2024 Oct 7;34(10):1630-1638. doi: 10.1136/ijgc-2024-005305. PMID: 38950921; PMCID: PMC11503204.
Grisham RN, Slomovitz BM, Andrews N, Banerjee S, Brown J, Carey MS, Chui H, Coleman RL, Fader AN, Gaillard S, Gourley C, Sood AK, Monk BJ, Moore KN, Ray-Coquard I, Shih IM, Westin SN, Wong KK, Gershenson DM. Low-grade serous ovarian cancer: expert consensus report on the state of the science. Int J Gynecol Cancer. 2023 Sep 4;33(9):1331-1344. doi: 10.1136/ijgc-2023-004610. PMID: 37591609; PMCID: PMC10511962.
Manning-Geist BL, Kahn RM, Nemirovsky D, Girshman J, Laibangyang A, Gordhandas S, Iasonos A, Chui MH, Long Roche K, Zivanovic O, Chi DS, Aghajanian C, Grisham RN. Chemotherapy response in low-grade serous ovarian carcinoma at a comprehensive cancer center: Readdressing the roles of platinum and cytotoxic therapies. Cancer. 2023 Jul 1;129(13):2004-2012. doi: 10.1002/cncr.34753. Epub 2023 Mar 23. PMID: 36951509; PMCID: PMC10682957.
Moujaber T, Balleine RL, Gao B, Madsen I, Harnett PR, DeFazio A. New therapeutic opportunities for women with low-grade serous ovarian cancer. Endocr Relat Cancer. 2021 Nov 11;29(1):R1-R16. doi: 10.1530/ERC-21-0191. PMID: 34636747.
Gershenson DM, Miller A, Brady WE, Paul J, Carty K, Rodgers W, Millan D, Coleman RL, Moore KN, Banerjee S, Connolly K, Secord AA, O'Malley DM, Dorigo O, Gaillard S, Gabra H, Slomovitz B, Hanjani P, Farley J, Churchman M, Ewing A, Hollis RL, Herrington CS, Huang HQ, Wenzel L, Gourley C. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022 Feb 5;399(10324):541-553. doi: 10.1016/S0140-6736(21)02175-9. PMID: 35123694; PMCID: PMC8819271.
Slomovitz BM, Weroha SJ, Deng W, Chon HS, Podder V, Jenkins Vogel MT, Backes F, Thomas ED, Chen LM, Tenney ME, Westin SN, Markham MJ, Miller DS, Edelson MI, Muller CY, Callahan MJ, Holman LL, Liu JR, Teplinsky E, Kamat A, Guy M, Chern JY, Lea J, Murphy M, Choong GM, Moore ED, Alvarez EA, Rodgers WH, O'Malley DM, Copeland LJ, Herzog TJ, Coleman RL, Gershenson DM. Phase II Trial of Ribociclib Plus Letrozole in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary, Fallopian Tube, or Peritoneum: A GOG Partners Trial (GOG 3026). J Clin Oncol. 2026 Jan 20;44(3):153-163. doi: 10.1200/JCO-25-01348. Epub 2025 Dec 12. PMID: 41385758.
Musacchio L, Turinetto M, Arenare L, Bartoletti M, Califano D, Tuninetti V, Marchetti C, Cormio G, Loizzi V, Pisano C, Salutari V, Valabrega G, Priolo D, Cecere SC, Ventriglia J, Raspagliesi F, Perrone F, Fagotti A, Lorusso D, Scambia G, Pignata S. Effect of bevacizumab in advanced low grade serous ovarian cancer: Data from the MITO 22 trial. Gynecol Oncol. 2023 May;172:72-77. doi: 10.1016/j.ygyno.2023.03.011. Epub 2023 Mar 23. PMID: 36965291.
Banerjee SN, Van Nieuwenhuysen E, Aghajanian C, D'Hondt V, Monk BJ, Clamp A, Prendergast E, Oaknin A, Ring K, Colombo N, Holloway RW, Rodrigues M, Chon HS, Gourley C, Santin AD, Thaker PH, Gennigens C, Newman G, Salinas E, Youssoufian H, Moore KN, Lustgarten S, O'Malley DM, Van Gorp T, Grisham RN. Efficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201. J Clin Oncol. 2025 Sep;43(25):2782-2792. doi: 10.1200/JCO-25-00112. Epub 2025 Jul 11. Erratum in: J Clin Oncol. 2025 Nov 10;43(32):3547. doi: 10.1200/JCO-25-02377. PMID: 40644648; PMCID: PMC12393057.
Referanslar
Kelliher L, Yoeli-Bik R, Schweizer L, Lengyel E. Molecular changes driving low-grade serous ovarian cancer and implications for treatment. Int J Gynecol Cancer. 2024 Oct 7;34(10):1630-1638. doi: 10.1136/ijgc-2024-005305. PMID: 38950921; PMCID: PMC11503204.
Grisham RN, Slomovitz BM, Andrews N, Banerjee S, Brown J, Carey MS, Chui H, Coleman RL, Fader AN, Gaillard S, Gourley C, Sood AK, Monk BJ, Moore KN, Ray-Coquard I, Shih IM, Westin SN, Wong KK, Gershenson DM. Low-grade serous ovarian cancer: expert consensus report on the state of the science. Int J Gynecol Cancer. 2023 Sep 4;33(9):1331-1344. doi: 10.1136/ijgc-2023-004610. PMID: 37591609; PMCID: PMC10511962.
Manning-Geist BL, Kahn RM, Nemirovsky D, Girshman J, Laibangyang A, Gordhandas S, Iasonos A, Chui MH, Long Roche K, Zivanovic O, Chi DS, Aghajanian C, Grisham RN. Chemotherapy response in low-grade serous ovarian carcinoma at a comprehensive cancer center: Readdressing the roles of platinum and cytotoxic therapies. Cancer. 2023 Jul 1;129(13):2004-2012. doi: 10.1002/cncr.34753. Epub 2023 Mar 23. PMID: 36951509; PMCID: PMC10682957.
Moujaber T, Balleine RL, Gao B, Madsen I, Harnett PR, DeFazio A. New therapeutic opportunities for women with low-grade serous ovarian cancer. Endocr Relat Cancer. 2021 Nov 11;29(1):R1-R16. doi: 10.1530/ERC-21-0191. PMID: 34636747.
Gershenson DM, Miller A, Brady WE, Paul J, Carty K, Rodgers W, Millan D, Coleman RL, Moore KN, Banerjee S, Connolly K, Secord AA, O'Malley DM, Dorigo O, Gaillard S, Gabra H, Slomovitz B, Hanjani P, Farley J, Churchman M, Ewing A, Hollis RL, Herrington CS, Huang HQ, Wenzel L, Gourley C. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022 Feb 5;399(10324):541-553. doi: 10.1016/S0140-6736(21)02175-9. PMID: 35123694; PMCID: PMC8819271.
Slomovitz BM, Weroha SJ, Deng W, Chon HS, Podder V, Jenkins Vogel MT, Backes F, Thomas ED, Chen LM, Tenney ME, Westin SN, Markham MJ, Miller DS, Edelson MI, Muller CY, Callahan MJ, Holman LL, Liu JR, Teplinsky E, Kamat A, Guy M, Chern JY, Lea J, Murphy M, Choong GM, Moore ED, Alvarez EA, Rodgers WH, O'Malley DM, Copeland LJ, Herzog TJ, Coleman RL, Gershenson DM. Phase II Trial of Ribociclib Plus Letrozole in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary, Fallopian Tube, or Peritoneum: A GOG Partners Trial (GOG 3026). J Clin Oncol. 2026 Jan 20;44(3):153-163. doi: 10.1200/JCO-25-01348. Epub 2025 Dec 12. PMID: 41385758.
Musacchio L, Turinetto M, Arenare L, Bartoletti M, Califano D, Tuninetti V, Marchetti C, Cormio G, Loizzi V, Pisano C, Salutari V, Valabrega G, Priolo D, Cecere SC, Ventriglia J, Raspagliesi F, Perrone F, Fagotti A, Lorusso D, Scambia G, Pignata S. Effect of bevacizumab in advanced low grade serous ovarian cancer: Data from the MITO 22 trial. Gynecol Oncol. 2023 May;172:72-77. doi: 10.1016/j.ygyno.2023.03.011. Epub 2023 Mar 23. PMID: 36965291.
Banerjee SN, Van Nieuwenhuysen E, Aghajanian C, D'Hondt V, Monk BJ, Clamp A, Prendergast E, Oaknin A, Ring K, Colombo N, Holloway RW, Rodrigues M, Chon HS, Gourley C, Santin AD, Thaker PH, Gennigens C, Newman G, Salinas E, Youssoufian H, Moore KN, Lustgarten S, O'Malley DM, Van Gorp T, Grisham RN. Efficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201. J Clin Oncol. 2025 Sep;43(25):2782-2792. doi: 10.1200/JCO-25-00112. Epub 2025 Jul 11. Erratum in: J Clin Oncol. 2025 Nov 10;43(32):3547. doi: 10.1200/JCO-25-02377. PMID: 40644648; PMCID: PMC12393057.
