The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial
Open accessAbstract
Background Based on preclinical work, we found that combination of poly (ADP-ribose) polymerase (PARP) inhibitors with drugs that inhibit the homologous recombination repair (HRR) pathway (such as PI3K inhibitors) might sensitise HRR-proficient epithelial ovarian cancers to PARP inhibitors. We aimed to assess the safety and identify the recommended phase 2 dose of the PARP inhibitor olaparib in combination with the PI3K inhibitor alpelisib in patients with epithelial ovarian cancer and in patients with breast cancer. Methods In this multicentre, open-label, phase 1b trial following a 3 + 3 dose-escalation design, we recruited patients aged 18 years or older with the following key eligibility criteria: confirmed diagnosis of either recurrent ovarian, fallopian tube, or primary peritoneal cancer of high-grade serous histology; confirmed diagnosis of either recurrent ovarian, fallopian tube, or primary peritoneal cancer of any histology with known germline BRCA mutations; confirmed diagnosis of recurrent breast cancer of triple-negative histology; or confirmed diagnosis of recurrent breast cancer of any histology with known germline BRCA mutations. Additional patients with epithelial ovarian cancer were enrolled in a dose-expansion cohort. Four dose levels were planned: the starting dose level of alpelisib 250 mg once a day plus olaparib 100 mg twice a day (dose level 0); alpelisib 250 mg once a day plus olaparib 200 mg twice a day (dose level 1); alpelisib 300 mg once a day plus olaparib 200 mg twice a day (dose level 2); and alpelisib 200 mg once a day plus olaparib 200 mg twice a day (dose level 3). Both drugs were administered orally, in tablet formulation. The primary objective was to identify the maximum tolerated dose and the recommended phase 2 dose of the combination of alpelisib and olaparib for patients with epithelial ovarian cancer and patients with breast cancer. Analyses included all patients who received at least one dose of the study drugs. The trial is active, but closed to enrolment; follow-up for patients who completed treatment is ongoing. This trial is registered with ClinicalTrials.gov, number NCT01623349. Findings Between Oct 3, 2014, and Dec 21, 2016, we enrolled 34 patients (28 in the dose-escalation cohort and six in the dose-expansion cohort); two in the dose-escalation cohort were ineligible at the day of scheduled study initiation. Maximum tolerated dose and recommended phase 2 dose were identified as alpelisib 200 mg once a day plus olaparib 200 mg twice a day (dose level 3). Considering all dose levels, the most common treatment-related grade 3-4 adverse events were hyperglycaemia (five [16%] of 32 patients), nausea (three [9%]), and increased alanine aminotransferase concentrations (three [9%]). No treatment-related deaths occurred. Dose-limiting toxic effects included hyperglycaemia and fever with decreased neutrophil count. Of the 28 patients with epithelial ovarian cancer, ten (36%) achieved a partial response and 14 (50%) had stable disease according to Response Evaluation Criteria in Solid Tumors 1.1. Interpretation Combining alpelisib and olaparib is feasible with no unexpected toxic effects. The observed activity provides preliminary clinical evidence of synergism between olaparib and alpelisib, particularly in epithelial ovarian cancer, and warrants further investigation. Funding Ovarian Cancer Dream Team (Stand Up To Cancer, Ovarian Cancer Research Alliance, National Ovarian Cancer Coalition), Breast Cancer Research Foundation, Novartis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In cancer cells, the PI3K/AKT pathway may be activated as a survival mechanism in response to the DNA damage caused by olaparib.”
From Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer (2024) · cites this paper as [41]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Integrated genomic analyses of ovarian carcinoma
Perou, C. M. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/hvp3-wg08 · Cited by 7,927
Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
Moore, K., Colombo, N., Scambia, G., Kim, B.-G., Oaknin, A., Friedlander, M., Lisyanskaya, A., Floquet, A., Leary, A., Sonke, G. S., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1810858 · Cited by 2,870 · cited 1×
“Finally, although nausea, fatigue and vomiting were observed in 50% or more of patients, these toxicities were mostly grade 1 and 2, easily manageable, and comparable to those observed with olaparib monotherapy (77% nausea, 63% fatigue and 40% vomiting in the recently reported SOLO1 study(22)).”
ResultSelf-citationNiraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer
Mirza, M. R., Monk, B. J., Herrstedt, J., Oza, A. M., Mahner, S., Redondo, A., Fabbro, M., Ledermann, J. A., Lorusso, D., Vergote, I. B., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1611310 · Cited by 2,452
Self-citationAudeh, M. W., Carmichael, J., Penson, R. T., Friedlander, M., Powell, B., Bell-McGuinn, K. M., Scott, C., Weitzel, J. N., Oaknin, A., Loman, N., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60893-8 · Cited by 2,279
Self-citationPujade-Lauraine, É., Hilpert, F., Weber, B. E., Reuß, A., Poveda, A. M., Kristensen, G. B., Sorio, R., Vergote, I. B., Witteveen, P. O., Bamias, A., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.51.4489 · Cited by 1,660 · cited 1×
“The median duration of response and median PFS and OS observed in this population were also promising and in line with the results of AURELIA study in platinum resistant ovarian cancer (27) despite the fact that AURELIA involved a significantly less heavily pretreated patient population as it allowed patients with onl…”
ResultSwisher, E. M., Lin, K. K., Oza, A. M., Scott, C. L., Giordano, H., Sun, J., Konecny, G. E., Coleman, R. L., Tinker, A. V., O'Malley, D. M., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30559-9 · Cited by 1,196 · cited 1×
“The promise of PARPis in the management of EOC is tempered, however, by the fact that EOCs with intrinsic, de novo, HRR proficiency respond less than HRR-deficient carcinomas (5, 6).”
BackgroundSelf-citationGelmon, K. A., Tischkowitz, M. D., MacKay, H. J., Swenerton, K. D., Robidoux, A., Tonkin, K. S., Hirte, H. W., Huntsman, D. D., Clemons, M. J., Gilks, C. B., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70214-5 · Cited by 1,130 · cited 4×
“The promise of PARPis in the management of EOC is tempered, however, by the fact that EOCs with intrinsic, de novo, HRR proficiency respond less than HRR-deficient carcinomas (5, 6).”
BackgroundInfluentialSecondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers
Sakai, W., Swisher, E. M., Karlan, B. Y., Agarwal, M. K., Higgins, J., Friedman, C., Villegas, E., Jacquemont, C., Farrugia, D. J., Couch, F. J., et al. (2008) · Nature · doi:10.1038/nature06633 · Cited by 1,086
Self-citationFong, P. C. C., Yap, T. A., Boss, D. S., Carden, C. P., Mergui‐Roelvink, M., Gourley, C., Grève, J. D., Lubiński, J., Shanley, S., Messiou, C., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.9589 · Cited by 1,022
Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer
Konstantinopoulos, P. A., Ceccaldi, R., Shapiro, G. I., & D'Andrea, A. D. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0714 · Cited by 945
Self-citation
Cited by
Sorted by citations
The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism
Hoxhaj, G., & Manning, B. D. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0216-7 · Cited by 2,137
PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer
Glaviano, A., Foo, A. S. C., Lam, H. Y., Yap, K. C. H., Jacot, W., Jones, R. H., Eng, H., Nair, M. G., Makvandi, P., Geoerger, B., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01827-6 · Cited by 2,138
“therapy in breast cancer [228] and other advanced solid tumors [229, 230], as well as in combination with either trastuzumab-emtansine [231], fulvestrant [232–235], letrozole [236–239], nab-paclitaxel [240], olaparib [241], or trastuzumab + LJM716 [242], in breast cancer, and in combination with either imatinib [243],…”
BackgroundRecent advances in therapeutic strategies for triple-negative breast cancer
Li, Y., Zhang, H., Merkher, Y., Chen, L., Liu, N., Leonov, S. V., & Chen, Y. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01341-0 · Cited by 1,035
Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer
Yu, L., Wei, J., & Liu, P. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.06.019 · Cited by 818
PARP and PARG inhibitors in cancer treatmentPreprint
Slade, D. (2020) · Genes & Development · doi:10.1101/gad.334516.119 · Cited by 693
“A phase I clinical trial revealed synergistic effects between olaparib and the PI3K inhibitor alpelisib in epithelial ovarian cancer, which are most likely based on HR suppression through reduced RAD51 protein levels and RAD51 foci formation (Konstantinopoulos et al. 2019).”
PI3K inhibitors are finally coming of age
Vanhaesebroeck, B., Perry, M. W. D., Brown, J. R., André, F., & Okkenhaug, K. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00209-1 · Cited by 494
PARP Inhibitor Resistance: A Tug-of-War in BRCA-Mutated Cells
Noordermeer, S. M., & van Attikum, H. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.07.008 · Cited by 472
The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design
Ling, Y., Hao, Z., Liang, D., Zhang, C., Liu, Y., & Wang, Y. (2021) · Drug Design Development and Therapy · doi:10.2147/dddt.s329547 · Cited by 428
DNA Repair Pathways in Cancer Therapy and Resistance
Li, L.-Y., Guan, Y.-D., Chen, X.-S., Yang, J.-M., & Cheng, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.629266 · Cited by 383
“…clinical trials for treatment of patients with BRCA1/2 mutation or HRR-deficiency advanced solid tumors, which shown promising clinical activity (Bang et al., 2017; Wilson et al., 2017; Loibl et al., 2018; Coleman et al., 2019; Farago et al., 2019; Konstantinopoulos et al., 2019; Liu et al., 2019).”
BackgroundSignaling Pathways in Cancer: Therapeutic Targets, Combinatorial Treatments, and New Developments
Yip, H. Y. K., & Papa, A. (2021) · Cells · doi:10.3390/cells10030659 · Cited by 341
“Based on pre-clinical results, a recent phase 1b trial has demonstrated synergism between olaparib and the PI3K p110α-specific inhibitor alpelisib in treating HR-proficient epithelial ovarian cancers [229].”
BackgroundPI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects
Mishra, R., Patel, H. M., Alanazi, S., Kilroy, M. K., & Garrett, J. T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073464 · Cited by 299
Konstantinopoulos, P. A., Cheng, S., Hendrickson, A. E. W., Penson, R. T., Schumer, S., Doyle, L. A., Lee, E. K., Kohn, E. C., Duska, L., Crispens, M. A., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(20)30180-7 · Cited by 229
Self-citationRadiotherapy as a tool to elicit clinically actionable signalling pathways in cancer
Petroni, G., Cantley, L. C., Santambrogio, L., Formenti, S. C., & Galluzzi, L. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00579-w · Cited by 224
Self-citationNew clinical trial design in precision medicine: discovery, development and direction
Duan, X.-P., Qin, B., Jiao, X., Liu, K., Wang, Z., & Zang, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01760-0 · Cited by 225
“163 – 170 CDK4/6: CDK4/6 inhibitor reverses the dilemma of endocrine resistance in breast cancer by alternating activation of CyclinD1 and ER.”
BackgroundZhang, H., Jiang, R., Zhu, J., Sun, K.-N., Huang, Y., Zhou, H., Zheng, Y., & Wang, X. (2024) · Breast Cancer · doi:10.1007/s12282-024-01567-5 · Cited by 210
“These results provide preliminary clinical evidence for the synergy between PI3K and PARP inhibitors [50, 51].”
ResultIntegrins in cancer: Emerging mechanisms and therapeutic opportunities
Liu, F., Wu, Q., Dong, Z., & Liu, K. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108458 · Cited by 202
PARP inhibitors: enhancing efficacy through rational combinations
Bhamidipati, D., Haro-Silerio, J. I., Yap, T. A., & Ngoi, N. Y. L. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02326-7 · Cited by 183
“In patients with recurrent and predominantly platinum-resistant ovarian cancer, ORR was 36% with responses seen among those without germline HRR mutations [47].”
BackgroundVasan, N., & Cantley, L. C. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00633-1 · Cited by 172
Self-citationTargeting the PI3K pathway and DNA damage response as a therapeutic strategy in ovarian cancer
Huang, T., Lampert, E. J., Coots, C., & Lee, J. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.102021 · Cited by 161
Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016–2022)
Shabir, G., Saeed, A., Zahid, W., Naseer, F., Riaz, Z., Khalil, N., Muneeba, M., & Alberício, F. (2023) · Pharmaceuticals · doi:10.3390/ph16081162 · Cited by 162
Huang, J., Chen, L., Wu, J., Ai, D., Zhang, J., Chen, T., & Wang, L. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01070 · Cited by 159
Signaling pathways in macrophages: molecular mechanisms and therapeutic targets
Li, M., Wang, M., Wen, Y., Zhang, H., Zhao, G., & Gao, Q. (2023) · MedComm · doi:10.1002/mco2.349 · Cited by 165
Paradigm Shift: A Comprehensive Review of Ovarian Cancer Management in an Era of Advancements
Tavares, V., Marques, I. S., de Melo, I. G., Assis, J., Pereira, D., & Medeiros, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031845 · Cited by 156
Chemotherapy resistance in epithelial ovarian cancer: Mechanisms and emerging treatments
Marchetti, C., De Felice, F., Romito, A., Iacobelli, V., Sassu, C. M., Corrado, G., Ricci, C., Scambia, G., & Fagotti, A. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.08.011 · Cited by 139
Yap, T. A., Kristeleit, R. S., Michalarea, V., Pettitt, S. J., Lim, J. S. J., Carreira, S., Roda, D., Miller, R. E., Riisnaes, R., Miranda, S., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0163 · Cited by 134
“with the -specific PI3K inhibitor alpelisib (15).”
BackgroundBoussios, S., Karihtala, P., Moschetta, M., Karathanasi, A., Sadauskaite, A., Rassy, E., & Pavlidis, N. A. (2019) · Diagnostics · doi:10.3390/diagnostics9030087 · Cited by 129
“Subsequently, a phase I trial evaluated the combination of olaparib with alpelisib, which is a more specific PI3K-alpha inhibitor [69].”
BackgroundClinical approaches to overcome PARP inhibitor resistance
Zou, Y., Zhang, H., Chen, P., Tang, J., Yang, S., Nicot, C., Guan, Z., Li, X., & Tang, H. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02355-1 · Cited by 118
“Furthermore, preliminary clinical evidence suggests synergistic activity between Olaparib and the PI3 K inhibitor Alpelisib [204].”
Nanomedicines inhibiting tumor metastasis and recurrence and their clinical applications
Kong, X., Cheng, R., Wang, J., Fang, Y., & Hwang, K. C. (2020) · Nano Today · doi:10.1016/j.nantod.2020.101004 · Cited by 93
Therapeutic Targeting of DNA Damage Response in Cancer
Choi, W., & Lee, E. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031701 · Cited by 97
“The combination was both tolerable and effective, especially in epithelial ovarian cancer (N = 28), with 10 patients (36%) achieving a partial response and 50% showing stable disease [154].”
BackgroundRinne, N., Christie, E. L., Ardasheva, A., Kwok, C. H., Demchenko, N., Low, C. M. R., Tralau, C. J., Fotopoulou, C., & Cunnea, P. (2021) · Cancer Drug Resistance · doi:10.20517/cdr.2021.05 · Cited by 97
PARP Inhibitors Resistance: Mechanisms and Perspectives
Giudice, E., Gentile, M., Salutari, V., Ricci, C., Musacchio, L., Carbone, M. V., Ghizzoni, V., Camarda, F., Tronconi, F., Nero, C., et al. (2022) · Cancers · doi:10.3390/cancers14061420 · Cited by 95
“Besides, the combination of PI3K inhibitors and PARPis has also been tested in clinical studies; in particular, the alpha specific PI3K inhibitor alpelisib (BYL719) has demonstrated to be safe in a multicenter, open-label, phase 1b trial [62] and a phase III trial is currently ongoing to investigate the efficacy of th…”
BackgroundThe PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer
Turnham, D. J., Bullock, N., Dass, M. S., Staffurth, J. N., & Pearson, H. B. (2020) · Cells · doi:10.3390/cells9112342 · Cited by 85
Westin, S. N., Labrie, M., Litton, J. K., Blucher, A., Fang, Y., Vellano, C. P., Marszalek, J. R., Feng, N., Ma, X., Creason, A., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-1656 · Cited by 84
“However, these trials failed to reach the maximum tolerated olaparib dose due to overlapping toxicity (14, 15).”
BackgroundMethodResultSelf-citationLuo, L., & Keyomarsi, K. (2022) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2022.2067527 · Cited by 79
“In addition, combining alpelisib and olaparib is feasible with no unexpected toxic effects, and the common adverse effects are hyperglycemia and nausea [118] (Table 4).”
BackgroundThe strategies to cure cancer patients by eradicating cancer stem-like cells
Mai, Y., Su, J., Yang, C., Xia, C., & Fu, L. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01867-y · Cited by 78
“PI3K inhibitor, alpelisib, provided preliminary clinical activity in epithelial ovarian cancer [149].”
BackgroundMohyuddin, G. R., Aziz, M., Britt, A., Lee‐Smith, W., Sun, W., Baranda, J. C., Al-Rajabi, R. M. T., Saeed, A., & Kasi, A. (2020) · BMC Cancer · doi:10.1186/s12885-020-06948-5 · Cited by 78
PARP Inhibitor Resistance Mechanisms and Implications for Post-Progression Combination Therapies
Lee, E. K., & Matulonis, U. A. (2020) · Cancers · doi:10.3390/cancers12082054 · Cited by 74
“Similarly, a phase Ib trial of alpelisib (PI3Ki) with olaparib in patients with EOC found that 35% (n = 6/17) of patients with germline BRCAwt disease achieved partial responses, similar to those with germline BRCA mutations (30%, n = 3/10) [130].”
Self-citationBatalini, F., Xiong, N., Tayob, N., Polak, M. M., Eismann, J., Cantley, L. C., Shapiro, G. I., Adalsteinsson, V. A., Winer, E. P., Konstantinopoulos, P. A., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-3045 · Cited by 73
Self-citationNew drug approvals for 2019: Synthesis and clinical applications
Yuan, S., Yu, B., & Liu, H. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112667 · Cited by 68
Synergistic effects of type I PRMT and PARP inhibitors against non-small cell lung cancer cells
Dominici, C., Sgarioto, N., Yu, Z., Sesma-Sanz, L., Masson, J., Richard, S., & Raynal, N. J. ‐. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01037-1 · Cited by 66
Rasti, A. R., Guimarães-Young, A., Datko, F. M., Borges, V. F., Aisner, D. L., & Shagisultanova, E. I. (2022) · JCO Precision Oncology · doi:10.1200/po.21.00370 · Cited by 66
Sun, X., Tang, H., Chen, Y., Chen, Z., Hu, Z., Cui, Z., Tao, Y., Yuan, J., Fu, Y., Zhuang, Z., et al. (2023) · Nature Cancer · doi:10.1038/s43018-023-00535-w · Cited by 66
Veneris, J. T., Matulonis, U. A., Liu, J. F., & Konstantinopoulos, P. A. (2019) · Gynecologic Oncology · doi:10.1016/j.ygyno.2019.09.021 · Cited by 62
Self-citationLeng, J., Li, H., Niu, Y., Chen, K., Yuan, X., Chen, H., Fu, Z., Zhang, L., Wang, F., Chen, C., et al. (2021) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2021.147990 · Cited by 62
Zhang, S., Peng, X., Li, X., Liu, H., Zhao, B., Elkabets, M., Liu, Y., Wang, W., Wang, R., Zhong, Y., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03805-6 · Cited by 62
Wu, Y., Xu, S., Cheng, S., Yang, J., & Wang, Y. (2023) · Journal of Ovarian Research · doi:10.1186/s13048-023-01094-5 · Cited by 60
Therapeutic strategies of dual-target small molecules to overcome drug resistance in cancer therapy
Ye, J., Wu, J., & Liu, B. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188866 · Cited by 63
Everything Comes with a Price: The Toxicity Profile of DNA-Damage Response Targeting Agents
Martorana, F., da Silva, L. A., Sessa, C., & Colombo, I. (2022) · Cancers · doi:10.3390/cancers14040953 · Cited by 61
PARP Inhibitors in Breast and Ovarian Cancer
Wang, S. S. Y., Jie, Y. E., Cheng, S. W., Ling, G. L., & Heong, V. Y. M. (2023) · Cancers · doi:10.3390/cancers15082357 · Cited by 60
“In the same study of 34 patients with recurrent epithelial ovarian cancer, alpelisib in combination with olaparib demonstrated a partial response of 36% with 50% achieving stable disease [95].”
BackgroundPARP inhibitors in ovarian cancer: overcoming resistance with combination strategies
Miller, R. E., El-Shakankery, K. H., & Lee, J. (2022) · Journal of Gynecologic Oncology · doi:10.3802/jgo.2022.33.e44 · Cited by 55
“There was an ORR of 36%, independent of germline HRR gene mutation status [64].”
BackgroundOvercoming PARP inhibitor resistance in ovarian cancer: what are the most promising strategies?
Klotz, D. M., & Wimberger, P. (2020) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-020-05677-1 · Cited by 54
Vidula, N., Rich, T. A., Sartor, O. A., Yen, J. L., Hardin, A. I., Nance, T., Lilly, M. B., Nezami, M. A., Patel, S. P., Carneiro, B. A., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2933 · Cited by 49
Bellare, G. P., & Patro, B. S. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115024 · Cited by 50
Ali, M., Lu, M., Ang, H. X., Soderquist, R. S., Eyler, C. E., Hutchinson, H. M., Glass, C., Bassil, C. F., Lopez, O. M., Kerr, D. L., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abc7480 · Cited by 52
Genomic profiling of platinum-resistant ovarian cancer: The road into druggable targets
da Costa, A. A. B. A., & Baiocchi, G. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.10.016 · Cited by 48
Alpelisib for PIK3CA-mutated advanced gynecological cancers: First clues of clinical activity
Passarelli, A. M., Carbone, V., Pignata, S., Mazzeo, R., Lorusso, D., Scambia, G., Canova, S., Palma, T. D., Tasca, G., Mantiero, M., et al. (2024) · Gynecologic Oncology · doi:10.1016/j.ygyno.2024.02.029 · Cited by 46
van der Ploeg, P., Uittenboogaard, A., Thijs, A. M. J., Westgeest, H. M., Boere, I. A., Lambrechts, S., van de Stolpe, A., Bekkers, R. L. M., & Piek, J. M. J. (2021) · Gynecologic Oncology · doi:10.1016/j.ygyno.2021.07.008 · Cited by 46
Peng, X., Zhang, S., Jiao, W., Zhong, Z., Yang, Y., Claret, F. X., Elkabets, M., Wang, F., Wang, R., Zhong, Y., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02176-2 · Cited by 48
“Based on these findings, a number of clinical studies are being carried out on PI3Kis in combination with RARP inhibitors in various types of cancers [83, 84].”
PARP-inhibitors in epithelial ovarian cancer: Actual positioning and future expectations
Vanacker, H., Harter, P., Labidi‐Galy, S. I., Banerjee, S. N., Oaknin, A., Lorusso, D., & Ray-Coquard, I. L. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102255 · Cited by 46
Collet, L., Hanvic, B., Turinetto, M., Treilleux, I., Chopin, N., Saux, O. L., & Ray-Coquard, I. L. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1354427 · Cited by 43
Thibault, B., Ramos-Delgado, F., & Guillermet-Guibert, J. (2023) · Cancers · doi:10.3390/cancers15030784 · Cited by 40
“A phase I clinical trial showed an indication of a synergy between the PI3Kα-specific inhibitor alpelisib and the PARP inhibitor olaparib in epithelial ovarian cancer [24].”
BackgroundChu, Y., Chen, M., Wei, Y., Lee, H., Xia, W., Wang, Y., Yam, C., Hsu, J. L., Wang, H.-L., Chang, W., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00438-2 · Cited by 40
Self-citationThe role of PARP inhibitor combination therapy in ovarian cancer
Hockings, H., & Miller, R. E. (2023) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359231173183 · Cited by 44
The regulatory role of PI3K in ageing-related diseases
Liu, Y., Liu, Q., Zhang, Z., Yang, Y., Zhou, Y., Yan, H., Wang, X. L., Li, X., Zhao, J., Hu, J., et al. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101963 · Cited by 39
Konstantinopoulos, P. A., Cheng, S., Supko, J. G., Polak, M. M., Wahner-Hendrickson, A. E., Ivy, S. P., Bowes, B., Sawyer, H., Basada, P., Hayes, M., et al. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01664-8 · Cited by 39
“agents which directly or indirectly inhibit HRR, is a promising strategy to overcome acquired PARPi resistance in HRR-deficient tumours as well as de novo PARPi resistance in HRR-proficient tumours [2, 3].”
BackgroundSelf-citationZhang, C., Lin, X., Zhao, Q., Wang, Y., Jiang, F., Ji, C., Li, Y., Gao, J., Li, J., & Shen, L. (2020) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-019-03115-7 · Cited by 38
Martins, F. C., Couturier, D., de Santiago, I., Sauer, C. M., Vias, M., Angelova, M., Sanders, D. A., Piskorz, A., Hall, J. A. M., Hosking, K., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33870-0 · Cited by 41
Tao, M., Sun, F., Wang, J., Wang, Y., Zhu, H., Chen, M., Liu, L., Liu, L., Lin, H., & Wu, X. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106232 · Cited by 38
PI3KCA Mutations in Uterine Cervix Carcinoma
Voutsadakis, I. A. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10020220 · Cited by 35
“Activity of alpelisib with olaparib has been observed in platinum refractory pretreated ovarian cancer patients with a response rate of 36% [32].”
BackgroundTao, M., & Wu, X. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02139-7 · Cited by 35
“Data from early phase demonstrate an efficacy (ORR 36%) of olaparib and the α specific PI3K inhibitor apelisib, which provides preliminary clinical evidence of synergism between olaparib and alpelisib, particularly in EOC [98].”
BackgroundOncogenic Pathways and Targeted Therapies in Ovarian Cancer
Lliberos, C., Richardson, G. E., & Papa, A. (2024) · Biomolecules · doi:10.3390/biom14050585 · Cited by 38
Systems approach to rational combination therapy: PARP inhibitors
Sun, C., Fang, Y., Labrie, M., Li, X., & Mills, G. B. (2020) · Biochemical Society Transactions · doi:10.1042/bst20191092 · Cited by 35
Self-citationArend, R. C., Jackson-Fisher, A. J., Jacobs, I. A., Chou, J., & Monk, B. J. (2021) · Cancer Biology & Therapy · doi:10.1080/15384047.2020.1868937 · Cited by 35
“Preclinical studies have shown that PI3K inhibitors may impair homologous recombination repair and sensitize ovarian cancer cells to PARP inhibitors.(98) Results from a phase Ib combination study of alpelisib with olaparib, in patients with recurrent ovarian cancer after prior platinum-based therapy, indicated a parti…”
BackgroundRole of Olaparib as Maintenance Treatment for Ovarian Cancer: The Evidence to Date
Montemorano, L., Lightfoot, M. D. S., & Bixel, K. L. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s195552 · Cited by 34
Wang, N., Yan, Y., Jin, D., Zhang, Z., Shen, K., Yang, J., Chen, H., Zhao, X., Li, Y., & Lu, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.967633 · Cited by 36
“responses in 36% and stable disease in 50% of 28 patients with BRCA wild-type OC(Konstantinopoulos et al., 2019).”
BackgroundUpdate on Combination Strategies of PARP Inhibitors
Lin, Z., Wang, L., Xing, Z., Wang, F., & Cheng, X. (2024) · Cancer Control · doi:10.1177/10732748241298329 · Cited by 37
“48 In a phase IIb clinical trial, 17 patients with recurrent breast cancer, including those with TNBC and other subtypes, were selected based on their germline BRCA mutation status.”
BackgroundStrategies in Overcoming Homologous Recombination Proficiency and PARP Inhibitor Resistance
Goel, N., Foxall, M. E., Scalise, C. B., Wall, J., & Arend, R. C. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0992 · Cited by 34
Ovarian cancer targeted therapy: current landscape and future challenges
Wang, G., Yang, H., Wang, Y., & Qin, J. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1535235 · Cited by 39
Lengyel, C. G., Altuna, S. C., Habeeb, B. S., Trapani, D., & Khan, S. Z. (2019) · Current Drug Targets · doi:10.2174/1389450120666191120123612 · Cited by 31
Development of Next-Generation Poly(ADP-Ribose) Polymerase 1–Selective Inhibitors
Ngoi, N. Y. L., Leo, E., O'Connor, M. J., & Yap, T. A. (2021) · The Cancer Journal · doi:10.1097/ppo.0000000000000556 · Cited by 32
Mehlich, D., & Marusiak, A. A. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215775 · Cited by 34
PBK drives PARP inhibitor resistance through the TRIM37/NFκB axis in ovarian cancer
Ma, H., Qi, G., Han, F., Peng, J., Yuan, C., & Kong, B. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00809-w · Cited by 31
Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises
Skorda, A., Bay, M. L., Hautaniemi, S., Lahtinen, A., & Kallunki, T. (2022) · Cancers · doi:10.3390/cancers14246257 · Cited by 31
PARP Inhibitors: Strategic Use and Optimal Management in Ovarian Cancer
Hirschl, N., Leveque, W., Granitto, J., Sammarco, V., Fontillas, M., & Penson, R. T. (2024) · Cancers · doi:10.3390/cancers16050932 · Cited by 32
“Olaparib and alpelisib, a PI3K inhibitor that is also part of the homologous recombination repair pathway, reported an ORR of 36% [24].”
BackgroundLabrie, M., Li, A., Creason, A., Betts, C. B., Keck, J. M., Johnson, B., Sivagnanam, S., Boniface, C. T., Ma, H., Blucher, A., et al. (2021) · npj Precision Oncology · doi:10.1038/s41698-021-00232-w · Cited by 31
Self-citationZhang, C., Sheng, Y., Sun, X., & Wang, Y. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10113-2 · Cited by 33
“Olaparib and alpelisib, a PI3K-alpha inhibitor, were combined in a multicenter, open-label, phase Ib trial in the 28 recurrent EOC patients with high-grade serous histology, and 36% of participants achieved partial response and 50% showed stable disease [264].”
MethodParp Inhibitors: A Tsunami of Indications in Different Malignancies
Haddad, G., Saadé, M. C., Eid, R., Haddad, F., & Kourié, H. R. (2020) · Pharmacogenomics · doi:10.2217/pgs-2019-0113 · Cited by 29
PARPi after PARPi in epithelial ovarian cancer
Essel, K. G., Behbakht, K., Lai, T. S., Hand, L. C., Evans, E. T., Dvořák, J., Ding, K., Konecny, G. E., & Moore, K. N. (2021) · Gynecologic Oncology Reports · doi:10.1016/j.gore.2021.100699 · Cited by 27
“%) had mixed EOC (one with mixed high grade serous and high grade endometrioid, and the other with mixed high grade endometrioid and clear cell EOC).”
BackgroundInfluentialEskiler, G. G., & Öztürk, M. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.110229 · Cited by 28
Combination Treatment Strategies to Overcome PARP Inhibitor Resistance
Soung, Y. H., & Chung, J. (2023) · Biomolecules · doi:10.3390/biom13101480 · Cited by 27
“%) monotherapy in patients with platinum-resistant epithelial ovarian cancer [89].”
BackgroundPARP Inhibitors in Gynecologic Cancers: What Is the Next Big Development?
Lightfoot, M. D. S., Montemorano, L., & Bixel, K. L. (2020) · Current Oncology Reports · doi:10.1007/s11912-020-0873-4 · Cited by 25
Sun, H. K., Cui, G., Shang, H., & Cui, B. (2020) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.0c02086 · Cited by 25
Polajžer, S., & Černe, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062545 · Cited by 28
“The synergistic activity between alpelisib and olaparib in platinum-resistant HGSOC of the BRCA wild-type has been shown in an EPIK-O/ENGOT-OV16 study, thereby extending the potential use of PARPis beyond the HRR-deficient context [115,133,134].”
Holzhauser, S., Lukoseviciute, M., Papachristofi, C., Vasilopoulou, C., Herold, N., Wickström, M., Kostopoulou, O. N., & Dalianis, T. (2021) · International Journal of Oncology · doi:10.3892/ijo.2021.5167 · Cited by 24
“Other studies have explored combinations of alpesilib with olaparib and erdafitinib with check point inhibitors (29,40).”
Leung, S. O. A., & Konstantinopoulos, P. A. (2021) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2021.1939305 · Cited by 24
“tions of PARPi with PI3K pathway inhibitors and combinations of PARPi and VEGFR inhibitors such as cediranib [37,38].”
BackgroundSelf-citationYe, Y., Huang, Z., Zhang, M., Li, J., Zhang, Y., & Lou, C. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114183 · Cited by 27
Elsayed, A. M., Bayraktar, E., Amero, P., Salama, S. A., Abdel‐Aziz, A. H., Ismail, R. S., Zhang, X., Ivan, C., Sood, A. K., Lopez‐Berestein, G., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041882 · Cited by 23
“The combination of alpelisib and olaparib has been shown to exhibit a synergistic effect against BRCA wild-type, platinum-resistant OC [52].”
BackgroundBao, S., Yue, Y., Hua, Y., Zeng, T., Yang, Y., Yang, F., Yan, X., Sun, C., Yang, M., Fu, Z., et al. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-1883 · Cited by 22
“The efficacy and safety of the combination therapy, including PARP inhibitors plus angiogenesis inhibitors (6,7), immune checkpoint inhibitors (8-10), cyclin dependent kinase (CDK) 4/6 inhibitors (11,12), phosphoinositide 3-kinase (PI3K) inhibitors (13), protein kinase B (AKT) inhibitors (14), mammalian target of rapa…”
BackgroundChu, X., Bu, Y., & Yang, X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.785855 · Cited by 24
Targeting PARP for the optimal immunotherapy efficiency in gynecologic malignancies
Li, T., Wang, X., Qin, S., Chen, B., Yi, M., & Zhou, J. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114712 · Cited by 24
Metadata
- Authors
- Konstantinopoulos, P. A., Barry, W. T., Birrer, M., Westin, S. N., Cadoo, K. A., Shapiro, G. I., Mayer, E. L., O'Cearbhaill, R. E., Coleman, R. L., Kochupurakkal, B., Whalen, C., Curtis, J., Farooq, S., Luo, W., Eismann, J., Buss, M. K., Aghajanian, C., Mills, G. B., Palakurthi, S., Kirschmeier, P., Liu, J., Cantley, L. C., Kaufmann, S. H., Swisher, E. M., D'Andrea, A. D., Winer, E., Wulf, G. M., & Matulonis, U. A.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Massachusetts General Hospital (US)
- The University of Texas MD Anderson Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Beth Israel Deaconess Medical Center (US)
- Oregon Health & Science University (US)
- Weill Cornell Medicine (US)
- Mayo Clinic (US)
- University of Washington (US)
- Corresponding author
- Konstantinopoulos, Panagiotis A
- ORCID
- Konstantinopoulos, Panagiotis A
- Birrer, Michael
- Westin, Shannon N
- Cadoo, Karen A
- Shapiro, Geoffrey I
- Mayer, Erica L
- O'Cearbhaill, Roisin E
- Coleman, Robert L
- Kochupurakkal, Bose
- Farooq, Sarah
- Buss, Mary K
- Aghajanian, Carol
- Mills, Gordon B
- Palakurthi, Sangeetha
- Liu, Joyce
- Cantley, Lewis C
- Kaufmann, Scott H
- Swisher, Elizabeth M
- Winer, Eric
- Wulf, Gerburg M
- Matulonis, Ursula A
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 20
- Issue
- 4
- Pages
- 570-580
- ISSN
- 1470-2045 (ISSN-L)
- PMC
- PMC7025391
- OpenAlex
- W2921991537
- Cited by
- 263
- References
- 33
- Citations by year
- 2026: 13 · 2025: 29 · 2024: 33 · 2023: 38 · 2022: 48 · 2021: 46 · 2020: 38 · 2019: 17
- FWCI
- 15.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Breast Cancer Research Foundation
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Keywords
- olaparib, alpelisib, PI3K inhibitors, PARP inhibitors, epithelial ovarian cancer, breast cancer, triple-negative breast cancer, homologous recombination repair, BRCA mutations, high-grade serous ovarian cancer, combination therapy, maximum tolerated dose, recommended phase 2 dose, drug safety, dose escalation, dose expansion, recurrent cancer, PARP inhibitor resistance
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Carcinoma, Ovarian Epithelial, Phosphoinositide-3 Kinase Inhibitors, Aged, Antineoplastic Combined Chemotherapy Protocols, Dose-Response Relationship, Drug, Female, Humans, Middle Aged, Mutation, Ovarian Neoplasms, Phthalazines, Piperazines, Thiazoles, Genome, Human, Treatment Outcome, Maximum Tolerated Dose, Drug-Related Side Effects and Adverse Reactions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
