PARPis after PARPis in patients with recurrent epithelial ovarian cancer: A single institutional experience

doi:10.21203/rs.3.rs-4905090/v1

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PARPis after PARPis in patients with recurrent epithelial ovarian cancer: A single institutional experience

https://doi.org/10.21203/rs.3.rs-4905090/v1

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Objective

Negligible evidence exists for PARPis maintenance treatment rechallenge in patients with recurrent epithelial ovarian cancer (EOC) in China.

Methods

We included patients diagnosed with primary EOC who received 2 lines of PARPis maintenance treatment after achieving complete response (CR) or partial response (PR) with the previous chemotherapies. The patients’ full medical records were included in this study. Clinical and pathologic variables, treatment modalities, and outcomes were assessed. We investigated the treatment patterns and time to next treatment (TTNT).

Results

A total of 31 ovarian cancer patients in our center were included. Among these patients, 20 of them (64.5%) had BRCA1/2 gene mutations. The median duration of PARPi1 and PARPi2 in the entire cohort was 11.2 months (range: 2.0-30.4 months) and 4.8 months (range: 1.0-16.7 months), respectively.

Median TTNT1 and TTNT2 for the entire cohort was 12.4 and 7.7 months, respectively. Patients with BRCA1/2 mutation had a significantly better TTNT1 (median TTNT1: 17.3 vs 10.4 months, P=0.005) than those without. A non- significantly better TTNT2 was observed in patients with BRCA1/2 mutation than those without (median TTNT2: 8.2 vs 5.0 months, P=0.890). The association between previous chemotherapy response and TTNT was also analyzed. Patients who had a CR to previous chemotherapy had a significantly better TTNT1 (median TTNT1: 16.4 vs 7.6 months, P=0.001) and TTNT2 (median TTNT2: 11.1 vs 4.9 months, P=0.003) than those who had a PR.

No grade Ⅲ-IV anemia occurred. Grade III PARPis-related thrombocytopenia was found in only 1 patient (3.2%, 1/31) who received PARPi2 treatment. For patients who developed PARPis-related anemia (n=9) or thrombocytopenia (n=7) during PARPi1 treatment, 7 patients (77.8%, 7/9) and 6 patients (85.7%, 6/7) developed anemia or thrombocytopenia again during PARPi2 treatment, respectively.

Conclusions

Patients with PARPis resistant recurrent EOC may derive benefit from PARPis re-treatment, especially for those with complete response to the last chemotherapy. Patients with BRCA1/2 mutation were more likely to benefit from PARPis retreatment than those with wild-type. Anemia and thrombocytopenia were more common in PARPis retreatment patients. A small proportion of patients had a longer benefit from PARPis retreatment than from previous PARPis treatment.

PARPis after PARPis

recurrent epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is a major cause of death in women worldwide.[1] There were approximately 314000 new cases of ovarian cancer diagnosed and 208000 deaths worldwide.[2] In 2022, there were approximately 61100 new cases of ovarian cancer diagnosed and 32600 deaths in China.[3] About 10%-15% ovarian cancer patients carry breast cancer susceptibility genes 1/2 (BRCA1/2) germline mutations.[4]

PARP (poly (ADP-ribose) polymerase) inhibitors (PARPis), are a type of anticancer treatment that works by preventing cancer cells from repairing DNA damage, especially in those with breast cancer susceptibility gene 1/2 (BRCA1/2) variants.[5] Clinical trials have demonstrated promising response rates among ovarian cancer patients receiving PARPis.[6–15] However, as also experienced with many other anticancer therapeutics, despite initial and often dramatic responses, patients receiving PARPis often ultimately develop treatment resistance.[16, 17]

The treatment consensus for patients with PARPis resistance has not been established. Retrospective study support that patients with recurrent EOC may derive benefit of the re-treatment with PARPis in case of clear response to the last platinum-based therapy.[18–20] The OReO/ENGOT Ov-38 trial is the first to provide data on PARPis rechallenge in platinum-sensitive recurrent ovarian cancer patients. Olaparib maintenance rechallenge provide a significant survival improvement, irrespective of BRCA1/2 mutation status.[20, 21] PARPis after PARPis is still an important challenge in patients with PARPis resistant EOC.[22]

Currently, the benefit of PARPis after PARPis has not been fully elucidated in Chinese EOC patients. In the current study, we investigated the treatment patterns and time to next treatment (TTNT) in patients diagnosed with primary EOC who received 2 lines of PARPis maintenance treatment after achieving complete response (CR) or partial response (PR) with the previous chemotherapies.

Patients

Following institutional review board approval, we performed a retrospective analysis of all patients diagnosed with primary EOC who received 2 lines of PARPis maintenance treatment after achieving CR or PR with the previous chemotherapies from January 1, 2018 to March 1, 2022 in the department of gynecological oncology of cancer hospital, Chinese academy of medical sciences, national cancer center. Only patients with a diagnosis of EOC confirmed by an experienced gynecologic pathologist in our hospital were included. Angiogenesis inhibitors such as bevacizumab or apatinib were not permitted as part of PARPis maintenance regimen.

Methods

Next-generation sequencing (NGS) for the entire coding regions and exon/intron boundaries of the BRCA1 and BRCA2 genes were conducted in all patients included in our study. The applied method of mutation screening was described in detail in our previous report.[23] Only those pathogenic variants that lead to a truncated protein or have been previously reported to be associated with disease were considered to be deleterious.

The patients’ full medical records were included in this study. Clinical and pathologic variables, treatment modalities, and outcomes were assessed. Stage was retrospectively assigned using the International Federation of Gynecology and Obstetrics (FIGO) 2014 staging system for ovarian cancer.

Statistical analyses

Time to next treatment (TTNT) is a useful real-world surrogate for progression free survival (PFS) in certain settings.[24] For the survival analyses, TTNT1 was defined as the time from initiating PARPi1 treatment to initiating the next line of therapy. TTNT2 was defined as the time from initiating PARPi2 treatment to initiating the next line of therapy. Overall survival (OS) was defined as the time from the date of diagnosis to death for which ovarian cancer was the primary or underlying cause. Survival was estimated using the Kaplan–Meier product-limit method, and differences were tested for statistical significance using the log-rank test. Two-sided P values less than 0.05 were considered to be statistically significant. All analyses were performed using the SPSS Statistics 20.0 software.

1. Clinicopathological characteristics

A total of 31 ovarian cancer patients who received 2 lines of PARPis maintenance treatment after achieving complete response (CR) or partial response (PR) with the previous chemotherapy in our center were included. Among these patients, 20 of them (64.5%) had BRCA1/2 gene mutations. Patients median age at diagnosis was 54 years (range: 35–76 years) (Table 1). 67.7% (21/31) of them were diagnosed after 50 years. The FIGO 2014 distribution by stage was: stage I in 1 patient (3.2%), stage II in 5 patient (16.1%), stage III in 19 patients (61.3%) and stage IV in 6 patient (19.4%) (Table 1). All patients had high-grade serous ovarian carcinoma. 27 patients (27/31, 87.1%) who had received cytoreduction surgery achieved R0/R1 resection (Table 1). For the first recurrence, 96.8% patients (30/31) were classified as platinum-sensitive recurrence, and only 1 patient (3.2%) was classified as platinum-resistant recurrence (Table 1).

Table 1

Clinicopathological characteristics of patients in the entire cohort
Clinical Characteristics	n	%
N	31
Median age (Range), years	54 (35–76)
Age at diagnosis (years)
<50	10	32.3
≥50	21	67.7
BMI (kg/m²)
<24	17	54.8
≥24	14	45.2
Tumor size (cm)
<5	7	22.6
≥5	24	77.4
BRCA1/2 status
Mutation	20	64.5
Wildtype	11	35.5
Histology
Serous ovarian cancer	29	93.5
Other	2	6.5
FIGO Stage
I	1	3.2
II	5	16.1
III	19	61.3
IV	6	19.4
Neoadjuvant chemotherapy
Yes	17	54.8
No	14	45.2
Postoperative residual disease status
Optimal (R0/R1)	27	87.1
Suboptimal (≥ R2)	4	12.9
First recurrence
Platinum-sensitive recurrence	30	96.8
Platinum-resistant recurrence	1	3.2
Response to previous chemotherapy of PARPi1
CR	17	54.8
PR	14	45.2
Response to previous chemotherapy of PARPi2
CR	7	22.6
PR	24	77.4
Abbreviations: BMI, body mass index; FIGO, International Federation of Gynecology and Obstetrics; CR, complete response; PR, partial response.

Response to previous chemotherapy of PARPi1 and PARPi2 was analyzed. For PARPi1, 17 (54.8%) and 14 (45.2%) patients had CR or PR for previous chemotherapy, respectively (Table 1). For PARPi2, 7 (22.6%) and 24 (77.4%) patients had CR or PR for previous chemotherapy, respectively (Table 1).

2. PARPi1 treatment

For PARPi1, 64.5% (20/31) patients received olaparib, 32.3% (10/31) patients received niraparib, and 3.2% (1/31) patients received fluzoparib (Table 2). 54.8% (17/31) patients received PARPi1 treatment after ≥ 2 lines of chemotherapy (range, 1–6). 45.2% (14/31), 54.8% (17/31) patients received PARPi1 for first line maintenance, or relapsed maintenance, respectively (Table 2). All patients discontinued PARPi1 treatment because of disease progression.

Table 2

PARPis treatment among the whole cohort
PARPi characteristics	PARPi 1		PARPi 2
PARPi characteristics	n	%	n	%
PARPi received
Fluzoparib	1	3.2	3	9.7
Olaprib	20	64.5	16	51.6
Niraparib	10	32.3	12	38.7
Number of previous chemotherapies
1	14	45.2	0	0.0
2	14	45.2	14	45.2
3	1	3.2	14	45.2
≥4	2	6.5	3	9.7
PARPi setting
First line maintenance	14	45.2	0	0.0
Relapsed maintenance	17	54.8	31	100.0
Reason for discontinuation of PARPi
Ongoing therapy	0	0.0	8	25.8
Progression	31	100.0	23	74.2

3. PARPi2 treatment

For PARPi2, 51.6% (16/31) patients received olaparib, 38.7% (12/31) patients received niraparib, and 9.7% (3/31) patients received fluzoparib (Table 2). 54.8% (17/31) patients received PARPi2 treatment after ≥ 3 lines of chemotherapy (range, 2–7). All patients received PARPi2 for relapsed maintenance treatment (Table 2). At the date of data cutoff, 8 patients (25.8%) continued to receive PARPis treatment. 23 patients (74.2%) patients discontinued PARPi2 treatment because of disease progression.

4. Duration of PARPi1 and PARPi2 treatment

The median duration of PARPi1 in the entire cohort was 11.2 months (range: 2.0-30.4 months). The median duration of PARPi1 for patients received first line maintenance, relapsed maintenance was 11.0 months (range: 2.0–19.3 months), 11.2 months (range: 2.1–30.4 months), respectively (Table 3). The median duration of PARPi2 in the entire cohort was 4.8 months (range: 1.0-16.7 months) (Table 3). Among patients who discontinued PARPi2 treatment (n = 23), 91.3% (21/23) patients had a longer duration of PARPi1 than PARPi2.

Table 3

Treatment duration of PARPi and PARPi2
PARPi characteristics		Median duration (range) (months)
PARPi1 duration
All		11.2 (2.0-30.4)
First line maintenance		11.0 (2.0-19.3)
Relapsed maintenance		11.2 (2.1–30.4)
PARPi2 duration
Relapsed maintenance		4.8 (1.0-16.7)

5. Survival analysis

The median follow-up was 46.5 months (range: 28.6–122.1 months). 5 patients (5/31, 16.1%) died during follow up. 5-year OS rate was 76.0% (Supplementary Fig. 1).

We further analyzed TTNT in this cohort. Median TTNT1 and TTNT2 for the entire cohort was 12.4 and 7.7 months, respectively. Patients with BRCA1/2 mutation had a significantly better TTNT1 (median TTNT1: 17.3 vs 10.4 months, P = 0.005, Fig. 1A). A better TTNT2 was observed in patients with BRCA1/2 mutation (median TTNT2: 8.2 vs 5.0 months); however, the difference was not statistically significant (P = 0.890, Fig. 1B). The association between previous chemotherapy response and TTNT was also analyzed. Patients who had a CR to previous chemotherapy had a significantly better TTNT1 (median TTNT1: 16.4 vs 7.6 months, P = 0.001, Fig. 2A) and TTNT2 (median TTNT2: 11.1 vs 4.9 months, P = 0.003, Fig. 2B) than those who had a PR.

6. Hematological toxicities of PARPi1 and PARPi2

During PARPi1 treatment, 9 patients (29.0%, 9/31) had PARPis-related anemia, including 16.1% (5/31) of grade Ⅰ and 12.9% (4/31) of grade Ⅱ, and no grade Ⅲ-IV anemia occurred. Among them, 4 patients (44.4%, 4/9) developed anemia within 4 weeks after PARPi1 treatment. During PARPi2 treatment, the incidence of PARPis-related anemia was 51.6% (16/31), all of which were grade I or II, and the incidence was 45.2% (14/31) and 6.5% (2/31), respectively. Ten patients (62.5%, 10/16) developed anemia within 4 weeks after PARPi2 treatment. For patients who developed PARPis-related anemia during PARPi1 treatment (n = 9), 7 patients (77.8%, 7/9) developed anemia again during PARPi2 treatment.

During PARPi1 treatment, 7 patients (22.6%, 7/31) had PARPis-related thrombocytopenia, including 16.1% (5/31) of grade Ⅰ and 6.5% (2/31) of grade Ⅱ, and no grade Ⅲ-IV thrombocytopenia occurred. During PARPi2 treatment, the incidence of PARPis-related thrombocytopenia was 38.7% (12/31), and the incidence was 19.4% (6/31), 16.1% (5/31) and 3.2% (1/31) for grade I-III, respectively. For patients who developed PARPis-related thrombocytopenia during PARPi1 treatment (n = 7), 6 patients (85.7%, 6/7) developed thrombocytopenia again during PARPi2 treatment. Thrombocytopenia of 12 patients (60.0%, 12/20) occurred within 8 weeks after PARPis treatment.

To our knowledge, the current study is one of the largest studies to report the use of PARPis as maintenance treatment among patients with recurrent EOC who have prior PARPis exposure. We found that patients with PARPis resistant recurrent EOC may derive benefit from PARPis maintenance treatment, especially for those with complete response to the last chemotherapies.

PARPis provide a promising treatment strategy that is potentially applicable to several stages of cancer progression.[16] However, durable responses of PARPis are uncommon and the development of acquired PARPis resistance often occurs during disease recurrence. The median duration of PARPi1 and PARPi2 in the entire cohort was 11.2 and 4.8 months, respectively. Most patients had a shorter duration of PARPi2 than PARPi1. It was worth noting that, 25.8% patients continued to receive PARPi2 treatment and the duration of PARPi2 would be longer.

Emerging evidence suggested that the opportunity for PARPis use after prior PARPis exposure exists.[18, 19, 25] The OReO/ENGOT Ov-38 trial was the first to provide data on PARPis rechallenge in platinum sensitive recurrent ovarian cancer patients.[25] Real-world data supported prospective evidence that patients with recurrent EOC may derive benefit of the re-treatment with PARPis in case of clear response to the last platinum-based therapy.[18] In the present study, 31 patients received PARPis retreatment which was the largest study in Chinese population.

Homologous recombination deficiency (HRD) and platinum sensitivity are prospective biomarkers for predicting the response to PARPis in ovarian cancers. Patients with BRCA1/2 mutant ovarian tumors benefit most from PARPis treatment. BRCA1/2 mutation is an important biomarker to select appropriate patients for PARPis treatment. We found BRCA1/2 mutations associated with a better response to PARPis in the entire cohort or the maintenance treatment subgroup. But the benefit of PARPis retreatment was limited for BRCA1/2 mutation carriers, as one recent study indicated that no difference of TTNT for PARPis retreatment between patients with BRCA1/2 mutation or wild-type.[26] The underlying reason may be the gradually developed resistance to PARPis for patients with BRCA1/2 mutation.

Response to platinum chemotherapy is also a strongly predictive of response to PARPis treatment. The present observation is consistent with these findings. We found patients who achieved a CR to the last chemotherapy appeared to receive longer TTNT2 benefit from PARPis retreatment than those with a PR. Other studies found CA-125 level and presence of visceral disease at baseline were the best predictors of patient outcome with PARPis retreatment.[21] Given the gradual increase of patients with PARPis resistant, there is a significant need to identify the biomarkers to select appropriate patients for PARPis retreatment.

Understanding and overcoming resistance to PARPis is important to PARPis retreatment choice. Acquired resistance to PARPis can develop via multiple mechanisms.[27, 28] Strategies designed to specifically target tumor cells with resistance to PARPis are still lacking.[16] Many combinatorial strategies aim to re-sensitize resistant cells to PARPis, such as ceralasertib + olaparib, niraparib + bevacizumab.[27, 29, 30] The exact role of PARPis after PARPis in EOC should be verified in more trials.

PARPis-related hematologic adverse effects including anemia, neutropenia, and thrombocytopenia are common with all the PARPis, but there are some notable differences between them.[6–15] Many patients have discontinued PARPis treatment because of anemia and thrombocytopenia. Thrombocytopenia is more frequent with niraparib than with other PARPis in the relapse setting. PARPis-related anemia mainly manifests as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin. In the present study, anemia and thrombocytopenia were more common in PARPis retreatment patients. Blood routine should be closely tested during PARPis retreatment.

There are two limitations to our study. The current study was retrospective, and the primary treatment was not assigned at randomized. All patients in this study came from our single center. Therefore, caution is required when interpreting our results. PARPis rechallenge should be studied in prospective manner.

Competing interests

No potential conflicts of interest were disclosed.

Human Ethics

This study was approved by the Research and Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences, National Cancer Center. Investigation was conducted in accordance with ethical standards, the Declaration of Helsinki and Chinese and international guidelines.

Consent to Participate declaration

Informed consent was diligently obtained from all enrolled patients.

Consent for publication

Not applicable.

Funding Declaration

This work was supported by Chinese Academy of Medical Sciences Cancer Hospital - Shenzhen Hospital Cooperation Fund (No. CFA202202018).

Authors' contributions

Conceptualization: L.N., W.T.H., Y.H.W., W.L.Y., Y.H.; Methodology: Y.H., W.T.H., L.N.; Validation: Y.H., W.T.H., L.N., W.L.Y.; Formal analysis and investigation: L.N., W.L.Y., Y.H.; Resources and data curation: Y.H., W.T.H.; Writing - original draft preparation: L.N., Y.H.; Writing - review and editing: L.N., Y.H., Y.H.W.; Supervision: Y.H.W., W.L.Y., L.N.; Project administration: Y.H., W.T.H.; Funding acquisition: Y.H., W.L.Y., L.N.. All authors have read and approved the manuscript.

Acknowledgements

We are indebted to all gynaecologists and others of Department of Gynecologic Oncology in our center for their support and their help in data collection.

Siegel RL, Miller KD, Fuchs HE, Jemal A, Cancer Statistics. 2021. CA Cancer J Clin. 2021;71:7–33.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021.
Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R et al. Cancer incidence and mortality in China, 2022. Journal of the National Cancer Center [Internet]. 2024 [cited 2024 Feb 2]; https://www.sciencedirect.com/science/article/pii/S2667005424000061
Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474:609–15.
Tattersall A, Ryan N, Wiggans AJ, Rogozińska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022;2:CD007929.
González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019;381:2391–402.
Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, et al. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019;381:2416–28.
Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, et al. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. N Engl J Med. 2019;381:2403–15.
Del Campo JM, Matulonis UA, Malander S, Provencher D, Mahner S, Follana P, et al. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019;37:2968–73.
Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20:636–48.
Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017;18:75–87.
Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:1949–61.
Moore K, Colombo N, Scambia G, Kim B-G, Oaknin A, Friedlander M, et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2018;379:2495–505.
Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:1274–84.
Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA, Bidziński M, et al. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020;38:1164–74.
Dias MP, Moser SC, Ganesan S, Jonkers J. Understanding and overcoming resistance to PARP inhibitors in cancer therapy. Nat Rev Clin Oncol. 2021;18:773–91.
Yuan H, Li N, Wu L, Yao H. Subsequent management and outcomes after first-line PARP inhibitors progression in ovarian cancer patients. J Ovarian Res. 2024;17:70.
Moubarak M, Harter P, Ataseven B, Traut A, Welz J, Baert T, et al. Re-treatment with PARPi in patients with recurrent epithelial ovarian cancer: A single institutional experience. Gynecol Oncol Rep. 2022;40:100939.
Essel KG, Behbakht K, Lai T, Hand L, Evans E, Dvorak J, et al. PARPi after PARPi in epithelial ovarian cancer. Gynecol Oncol Rep. 2021;35:100699.
Pujade-Lauraine E, Selle F, Scambia G, Asselain B, Marmé F, Lindemann K et al. Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial. Ann Oncol. 2023;S0923-7534(23)04007-3.
Selle F, Asselain B, Montestruc F, Bazan F, Pardo B, Salutari V, et al. OReO/ENGOT Ov-38 trial: Impact of maintenance olaparib rechallenge according to ovarian cancer patient prognosis—An exploratory joint analysis of the BRCA and non-BRCA cohorts. JCO. 2022;40:5558–5558.
Jou J, Kurzrock R, Zajchowski D, Eskander R. PARPi post PARPi: Clarity from the Clearity real world experience. Gynecol Oncol. 2022;166:S97.
Yuan H, Xiu L, Li N, Li Y, Wu L, Yao H. PARPis response and outcome of ovarian cancer patients with BRCA1/2 germline mutation and a history of breast cancer. J Gynecol Oncol. 2024.
Walker B, Boyd M, Aguilar K, Davies K, Espirito J, Frytak J, et al. Comparisons of Real-World Time-to-Event End Points in Oncology Research. JCO Clin Cancer Inf. 2021;5:45–6.
Pujade-Lauraine E. Maintenance olaparib rechallenge in patients (pts) with ovarian carcinoma (OC) previously treated with a PARP inhibitor (PARPi): Phase IIIb OReO/ENGOT Ov-38 trial. Ann Oncol. 2021;32:S1308–1309.
PARPi after PARPi. Clarity from the Clearity Real-World Experience. SGO. poster 164.
Lheureux S, Oaknin A, Garg S, Bruce JP, Madariaga A, Dhani NC, et al. EVOLVE: A Multicenter Open-Label Single-Arm Clinical and Translational Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer after PARP Inhibition Progression. Clin Cancer Res. 2020;26:4206–15.
Kristeleit R, Lisyanskaya A, Fedenko A, Dvorkin M, de Melo AC, Shparyk Y, et al. Rucaparib versus chemotherapy in patients with advanced, relapsed ovarian cancer and a deleterious BRCA mutation: efficacy and safety from ARIEL4, a randomized phase III study. Gynecol Oncol. 2021;162:S3–4.
McMullen M, Karakasis K, Loembe B, Dean E, Parr G, Oza AM. DUETTE: a phase II randomized, multicenter study to investigate the efficacy and tolerability of a second maintenance treatment in patients with platinum-sensitive relapsed epithelial ovarian cancer, who have previously received poly(ADP-ribose) polymerase (PARP) inhibitor maintenance treatment. Int J Gynecol Cancer. 2020;30:1824–8.
Park J, Lim MC, Lee J-K, Jeong DH, Kim SI, Choi MC, et al. A single-arm, phase II study of niraparib and bevacizumab maintenance therapy in platinum-sensitive, recurrent ovarian cancer patients previously treated with a PARP inhibitor: Korean Gynecologic Oncology Group (KGOG 3056)/NIRVANA-R trial. J Gynecol Oncol. 2022;33:e12.

No competing interests reported.

SupplementaryFigure1.pdf
Supplementary Figure 1. Overall survival analyses by the Kaplan–Meier method in the entire cohort (n=31).

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PARPis after PARPis in patients with recurrent epithelial ovarian cancer: A single institutional experience

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Abstract

Figures

Introduction

Patients and methods

Patients

Methods

Statistical analyses

Results

1. Clinicopathological characteristics

2. PARPi1 treatment

3. PARPi2 treatment

4. Duration of PARPi1 and PARPi2 treatment

5. Survival analysis

6. Hematological toxicities of PARPi1 and PARPi2

Discussion

Conclusion

Declarations

References

Additional Declarations

Supplementary Files

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