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Systemic treatment and management of recurrent ovarian cancer.

Dr. Noha Rashad.

Lecturer of medical oncology, faculty of medicine, Suez university.

CAIRO journal club co-founder and board member.

EFMS secretary general.

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Disclosures:

Travel grants: Roche, Bayer, Novartis and Pfizer.

Honorarium: Merck, Amgen, Bayer, Novartis, Roche, Sanofi, Servier and Lilly.

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Recurrent ovarian cancer.

1. Markman, M. et al. The Oncologist. 2000;5(1):26–35; 2. Hanker LC, et al. Ann Oncol. 2012;23(10):2605–2612; 3. Armstrong, D. K. The Oncologist 7, 20–28 (2002); 4.Fotopoulou, C. Eur. J. Cancer Suppl. 12, 13–16 (2014)

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The platinum “sensitive-resistant” paradigm.

Bouberhan et al. Status Published at jco.org on August 12, 2019.

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Challenging the platinum “sensitive-resistant” paradigm.

Platinum and non-platinum therapy in patients in first relapse with a ≤ 6 months platinum-free interval

PFI > 3-≤6 months:

Median OS from treatment: Platinum: 17.67 months (95% CI: 14.79–20.75) Non-platinum: 10.62 months (95% CI: 8.02–12.72) [P = 0.022].

Lindemann et al Gynecol Oncol 2018

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Treatment-oriented definition for systemic treatment of relapsed disease.

Platinum might not be the best option

(platinum in-eligible)

Early symptomatic relapse.
Progression on prior platinum-based therapy.
Platinum intolerability.

Platinum might be the best option

(platinum eligible)

Nicoletta Colombo et al. ESMO-ESGO consensus conference recommendations. Ann Oncol 02 May 2019

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Chemotherapy: when platinum is an option

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The CALYPSO trial- Carboplatin/PLD versus Carboplatin/Paclitaxel.

Pujade-Lauraine et al J Clin Oncol 2010; Wagner et al B J Cancer 2012

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Bevacizumab and PARPi in first relapse.

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Maintenance with Bevacizumab+platinum-based chemotherapy:

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Maintenance with bevacizumab:

Patients with ascites/pleural effusions.
Patients in whom rapid control of symptoms is needed.
Patients with prior PARP inhibitor

WORKING GROUP 4 RECOMMENDATIONS

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PARPi trials in relapsed OC:

Poveda A, et al. Lancet Oncol 2021;22:620–631; 2. Pignata S, et al. Gynecologic Oncol 2021;162:29; 3. Mirza MR, et al. N Engl J Med 2016;375:2154–2164; 4. Ledermann JA, et al. Ther Adv Med Oncol 2019;22:11; 5. Coleman RL, et al. The Lancet 2017;390:1949–1961; 6. Poveda A, et al. Gynecol Oncol 2022;164:498–504; 7. Domchek SM, et al. Gynecol Oncol 2016;140:199–203; 8. Penson RT, et al. J Clin Oncol 2020;38:1164–1174; 9. Moore K, et al. Lancet Oncol 2019;20:636–648; 10. Kristeleit R, et al. Lancet Oncol 2022;23:465–478; 11. Cadoo K, et al. Gynecol Oncol 2022;166:425–431

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Study 19: maintenance olaparib following response to platinum-based chemotherapy.

Ledermann J, et al. Lancet Oncol 2014

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Study 19 final OS:

Friedlander et al Br J Cancer 2018

Gourley C et al. J Clin Oncol 35, 2017 (suppl; poster related to abstr 5533)

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Efficacy of PARPi in patients with BRCA-mutant disease: Primary Endpoint, PFS.

Pujade-Lauraine E, et al. Lancet Oncol. 2017; 18(9):1274.1284 2. Mirza MR, et al. N Engl Med.2016;375(22):2154-2164 3. Coleman RL, et al. Lancet 2017; 390(10106): 1949-1961

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OS: ADJUSTING FOR PARP INHIBITOR CROSSOVER IN SOLO-2.

Poveda et al Lancet Oncol 2021;22(5):620–63

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How should we interpret recent OS data from trials investigating PARPi as maintenance in patients with BRCAm relapsed OC?

Matulonis, et al. Presented at 2021 Society of Gynecologic Oncology; 19th–25th March 2021; 2. Coleman R. Presented at International Gynecologic Cancer Society Annual Global Meeting, 29th September – 1st October 2022; New York City, NY, USA

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ENGOT-OV16/NOVA OS – gBRCAm Cohort.

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OS in non-gBRCAm,HRD+ cohort.

Coleman R. Presented at International Gynecologic Cancer Society Annual Global Meeting, 29th September – 1st October 2022; New York City, NY, US

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ENGOT-OV16/NOVA OS – Non-gBRCAm Cohort.

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Final Overall Survival for the gBRCAm and non-gBRCAm Cohorts.

Matulonis SGO 2023

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PARPi after PARPi.�Beva. After Beva.�Platinum after PARPi

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OREO trial: Rechallenge with PARP inhibitor – Olaparib.

Pujade-Lauraine E, et al. ESMO 2021. Presentation LBA33.

Secondary endpoint OS: Median OS in the BRCAm cohort was 20.1 months with olaparib and 20.9 months with placebo.

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ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer 2024.

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Re-treating with bevacizumab: MITO-MANGO 16b trial.

Pignata S, et al. Lancet Oncol. 2021;22:267–276.

Median progression-free survival was 8·8 months in the standard chemotherapy group and 11·8 months in the bevacizumab group (hazard ratio 0·51, 95% CI 0·41–0·65; log-rank p<0·0001)
No difference in OS.

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Does use of a PARPi in PSR OC have the potential to induce platinum resistance?

Post hoc analysis of SOLO-2 / ENGOT Ov-21.

Frenel JS, et al. Presented at European Society for Medical Oncology Congress 2020, 18th – 22nd September 2020; virtual

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Systemic treatment: when platinum is not an option.

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What defines platinum resistance and how does that influence subsequent treatment?

Colombo N, Sessa C, and D. Querleu et al. Annals of Oncology, Volume 30, Issue 5, May 2019, Pages 672–705 Colombo N, Sessa C, and D. Querleu et al. Int J Gynecol , Int J Gynecol Cancer 2019;29:728–760

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AURELIA: Chemotherapy vs chemo+beva.

Significant increased Progression-free survival with bevacizumab in platinum “resistant” recurrent ovarian cancer.

E Pujade-Laurine et al. JCO 2014