Advertisement

Poly (ADP-ribose) polymerase inhibitors in solid tumours: Systematic review and meta-analysis

Published:April 13, 2021DOI:https://doi.org/10.1016/j.ejca.2021.02.035

      Highlights

      • Twenty-nine trials with BRCA-mutant (mut) or wild-type (wt) cancers were included.
      • Progression-free survival (PFS) was improved by PARP-inhibitors (is), independent of BRCA.
      • Response rates were higher with PARPis, irrespective of BRCAstatus.
      • Overall survival was improved by PARPis, independent of BRCA mutational status.
      • PFS was improved by PARPis in cancers with homologous recombination deficiency.

      Abstract

      Background

      Poly (ADP-ribose) polymerase-inhibitors (PARPis) showed antitumour activity in BRCA1/2-mutated cancers, with more heterogeneous outcomes in tumours harbouring mutations that impair other genes involved in the DNA homologous recombination repair (HRR) or wild-type (wt).

      Methods

      We conducted a systematic review and meta-analysis to better assess the role of PARPis in the treatment of metastatic solid tumours, with and without BRCA1/2 mutations. The primary end-point was progression-free survival (PFS). The secondary end-points were overall response rate (ORR) and overall survival (OS). A random-effects model was applied.

      Results

      Twenty-nine studies (8,839 patients) were included. PFS was significantly improved (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.51–0.68, p < 0.001), without being affected by BRCA mutational status (p = 0.65). Significant subgroup differences were observed with regard to the tumour site (p = 0.001), line of therapy (p = 0.002), control arm (p < 0.001), type of PARPi (p < 0.001) and trials' phase (p = 0.006). PARPis were associated with ORR (relative risk: 1.35, 95% CI: 1.16–1.56, p < 0.001), with significant subgroup differences observed with regard to treatment line (p = 0.03), control arm (p = 0.04) and PARPis (p < 0.001) and independent of mutational status (p = 0.44), tumour site (p = 0.86) and trials' phase (p = 0.09). OS was significantly improved by PARPis (HR: 0.86, 95% CI: 0.80–0.92, p < 0.001), regardless of mutational status (p = 0.57), tumour site (p = 0.82), treatment line (p = 0.22), control arm (p = 0.21), PARPis (p = 0.30) and trials' phase (p = 0.26). Finally, an exploratory subgroup analysis showed a significant PFS improvement (HR: 0.51, 95% CI: 0.43–0.60, p < 0.001) with PARPis in BRCA-wt/HRR-deficient tumours.

      Conclusion

      Our results confirm the efficacy of already approved PARPi-based treatments in BRCA1/2-mutant solid tumours, support their role also in BRCA-independent HRR-deficient tumours and suggest a potentially broader efficacy in some wt tumours, perhaps with appropriate therapeutic partners. Prospective studies are warranted.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • National Cancer Institute
        Genetics of breast and gynecologic cancers (PDQ®) - health professional version.
        2019
        • Venkitaraman A.R.
        Cancer susceptibility and the functions of BRCA1 and BRCA2.
        Cell. 2002; 108: 171-182
        • Featherstone C.
        • Jackson S.P.
        DNA double-strand break repair.
        Curr Biol. 1999; 9: R759-R761
        • Wang J.Y.J.
        DNA damage and apoptosis.
        Cell Death Differ. 2001; 8: 1047-1048
        • Narod S.A.
        • Foulkes W.D.
        BRCA1 and BRCA2: 1994 and beyond.
        Nat Rev Cancer. 2004; 4: 665-676
      1. Susan G. Komen foundation. Inherited genetic mutations.

        • Bayraktar S.
        • Glück S.
        • Darling H.
        Update on PARP inhibitor therapy for solid tumours.
        J Cancer Prev Curr Res. 2019; 10: 98-107
        • Golan T.
        • Hammel P.
        • Reni M.
        • et al.
        Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer.
        N Engl J Med. 2019; 381: 317-327
        • McClain M.R.
        • Palomaki G.E.
        • Nathanson K.L.
        • Haddow J.E.
        Adjusting the estimated proportion of breast cancer cases associated with BRCA1 and BRCA2 mutations: public health implications.
        Genet Med Off J Am Coll Med Genet. 2005; 7: 28-33
        • Messina C.
        • Cattrini C.
        • Soldato D.
        • et al.
        BRCA mutations in prostate cancer: prognostic and predictive implications.
        J Oncol. 2020; https://doi.org/10.1155/2020/4986365
        • Manchana T.
        • Phoolcharoen N.
        • Tantbirojn P.
        BRCA mutation in high grade epithelial ovarian cancers.
        Gynecol Oncol Rep. 2019; 29: 102-105
        • Satoh M.S.
        • Lindahl T.
        Role of poly(ADP-ribose) formation in DNA repair.
        Nature. 1992; 356: 356-358
        • Lord C.J.
        • Ashworth A.
        PARP inhibitors: synthetic lethality in the clinic.
        Science. 2017; 355: 1152-1158
        • Farmer H.
        • McCabe N.
        • Lord C.J.
        • et al.
        Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.
        Nature. 2005; 434: 917-921
        • McCabe N.
        • Turner N.C.
        • Lord C.J.
        • et al.
        Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition.
        Cancer Res. 2006; 66: 8109-8115
        • Murai J.
        • Huang S.N.
        • Das B.B.
        • et al.
        Trapping of PARP1 and PARP2 by clinical PARP inhibitors.
        Cancer Res. 2012; 72: 5588-5599
        • Hopkins T.A.
        • Ainsworth W.B.
        • Ellis P.A.
        • et al.
        PARP1 trapping by PARP inhibitors drives cytotoxicity in both cancer cells and healthy bone marrow.
        Mol Cancer Res. 2019; 17: 409-419
        • Han H.S.
        • Diéras V.
        • Robson M.
        • et al.
        Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study.
        Ann Oncol Off J Eur Soc Med Oncol. 2018; 29: 154-161
        • Litton J.K.
        • Rugo H.S.
        • Ettl J.
        • et al.
        Talazoparib in patients with advanced breast cancer and a germline BRCA mutation.
        N Engl J Med. 2018; 379: 753-763
        • Robson M.E.
        • Tung N.
        • Conte P.
        • et al.
        OlympiAD final overall survival and tolerability results: olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer.
        Ann Oncol Off J Eur Soc Med Oncol. 2019; 30: 558-566
        • Robson M.
        • Im S.-A.
        • Senkus E.
        • et al.
        Olaparib for metastatic breast cancer in patients with a germline BRCA mutation.
        N Engl J Med. 2017; 377: 523-533
        • Gorbunova V.
        • Beck J.T.
        • Hofheinz R.-D.
        • et al.
        A phase 2 randomised study of veliparib plus FOLFIRI±bevacizumab versus placebo plus FOLFIRI±bevacizumab in metastatic colorectal cancer.
        Br J Cancer. 2019; 120: 183-189
        • Bang Y.-J.
        • Xu R.-H.
        • Chin K.
        • et al.
        Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial.
        Lancet Oncol. 2017; 18: 1637-1651
        • Owonikoko T.K.
        • Dahlberg S.E.
        • Sica G.L.
        • et al.
        Randomized phase II trial of cisplatin and etoposide in combination with veliparib or placebo for extensive-stage small-cell lung cancer: ECOG-ACRIN 2511 study.
        J Clin Oncol Off J Am Soc Clin Oncol. 2019; 37: 222-229
        • Pietanza M.C.
        • Waqar S.N.
        • Krug L.M.
        • et al.
        Randomized, double-blind, phase II study of temozolomide in combination with either veliparib or placebo in patients with relapsed-sensitive or refractory small-cell lung cancer.
        J Clin Oncol Off J Am Soc Clin Oncol. 2018; 36: 2386-2394
        • Ramalingam S.S.
        • Blais N.
        • Mazieres J.
        • et al.
        Randomized, placebo-controlled, phase II study of veliparib in combination with carboplatin and paclitaxel for advanced/metastatic non-small cell lung cancer.
        Clin Cancer Res Off J Am Assoc Cancer Res. 2017; 23: 1937-1944
        • Middleton M.R.
        • Friedlander P.
        • Hamid O.
        • et al.
        Randomized phase II study evaluating veliparib (ABT-888) with temozolomide in patients with metastatic melanoma.
        Ann Oncol Off J Eur Soc Med Oncol. 2015; 26: 2173-2179
        • Audeh M.W.
        • Carmichael J.
        • Penson R.T.
        • et al.
        Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial.
        Lancet Lond Engl. 2010; 376: 245-251
        • Coleman R.L.
        • Oza A.M.
        • Lorusso D.
        • 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 Lond Engl. 2017; 390: 1949-1961
        • Coleman R.L.
        • Fleming G.F.
        • Brady M.F.
        • et al.
        Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer.
        N Engl J Med. 2019; 381: 2403-2415
        • González-Martín A.
        • Pothuri B.
        • Vergote I.
        • et al.
        Niraparib in patients with newly diagnosed advanced ovarian cancer.
        N Engl J Med. 2019; 381: 2391-2402
        • Kaye S.B.
        • Lubinski J.
        • Matulonis U.
        • et al.
        Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer.
        J Clin Oncol Off J Am Soc Clin Oncol. 2012; 30: 372-379
        • Kummar S.
        • Oza A.M.
        • Fleming G.F.
        • et al.
        Randomized trial of oral cyclophosphamide and veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer.
        Clin Cancer Res Off J Am Assoc Cancer Res. 2015; 21: 1574-1582
        • Ledermann J.
        • Harter P.
        • Gourley C.
        • et al.
        Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer.
        N Engl J Med. 2012; 366: 1382-1392
        • Ledermann J.A.
        • Harter P.
        • Gourley C.
        • et al.
        Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial.
        Lancet Oncol. 2016; 17: 1579-1589
        • Liu J.F.
        • Barry W.T.
        • Birrer M.
        • et al.
        Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study.
        Lancet Oncol. 2014; 15: 1207-1214
        • Liu J.F.
        • Barry W.T.
        • Birrer M.
        • et al.
        Overall survival and updated progression-free survival outcomes in a randomized phase II study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer.
        Ann Oncol Off J Eur Soc Med Oncol. 2019; 30: 551-557
        • Mirza M.R.
        • Monk B.J.
        • Herrstedt J.
        • et al.
        Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer.
        N Engl J Med. 2016; 375: 2154-2164
        • Mirza M.R.
        • Åvall Lundqvist E.
        • Birrer M.J.
        • et al.
        Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial.
        Lancet Oncol. 2019; 20: 1409-1419
        • Moore K.
        • Colombo N.
        • Scambia G.
        • et al.
        Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer.
        N Engl J Med. 2018; 379: 2495-2505
        • Oza A.M.
        • Cibula D.
        • Benzaquen A.O.
        • et al.
        Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial.
        Lancet Oncol. 2015; 16: 87-97
        • Penson R.T.
        • Valencia R.V.
        • Cibula D.
        • 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 Off J Am Soc Clin Oncol. 2020; 38: 1164-1174
        • Pujade-Lauraine E.
        • Ledermann J.A.
        • Selle F.
        • 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: 1274-1284
        • Ray-Coquard I.
        • Pautier P.
        • Pignata S.
        • et al.
        Olaparib plus bevacizumab as first-line maintenance in ovarian cancer.
        N Engl J Med. 2019; 381: 2416-2428
        • Clarke N.
        • Wiechno P.
        • Alekseev B.
        • et al.
        Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial.
        Lancet Oncol. 2018; 19: 975-986
        • de Bono J.
        • Mateo J.
        • Fizazi K.
        • et al.
        Olaparib for metastatic castration-resistant prostate cancer.
        N Engl J Med. 2020; 382: 2091-2102
        • Mateo J.
        • Porta N.
        • Bianchini D.
        • et al.
        Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial.
        Lancet Oncol. 2020; 21: 162-174
        • Poveda A.
        • Floquet A.
        • Ledermann J.A.
        • et al.
        Final overall survival (OS) results from SOLO2/ENGOT-ov21: a phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation.
        J Clin Oncol. 2020; 38 (6002–6002)
        • Vikas P.
        • Borcherding N.
        • Chennamadhavuni A.
        • Garje R.
        Therapeutic potential of combining PARP inhibitor and immunotherapy in solid tumours.
        Front Oncol. 2020; https://doi.org/10.3389/fonc.2020.00570
      2. Clinical trial endpoints for the approval of cancer drugs and biologics. 2018: 19
        • Hussain M.
        • Mateo J.
        • Fizazi K.
        • et al.
        Survival with olaparib in metastatic castration-resistant prostate cancer.
        N Engl J Med. 2020; https://doi.org/10.1056/NEJMoa2022485
        • Diéras V.
        • Han H.S.
        • Kaufman B.
        • et al.
        Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial.
        Lancet Oncol. 2020; 21: 1269-1282
        • Litton J.K.
        • Hurvitz S.A.
        • Mina L.A.
        • et al.
        Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial.
        Ann Oncol Off J Eur Soc Med Oncol. 2020; 31: 1526-1535
        • Higgins J.P.T.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Stat Med. 2002; 21: 1539-1558
        • Borenstein M.
        • Hedges L.V.
        • Higgins J.P.T.
        • Rothstein H.R.
        A basic introduction to fixed-effect and random-effects models for meta-analysis.
        Res Synth Methods. 2010; 1: 97-111
        • Baujat B.
        • Mahé C.
        • Pignon J.-P.
        • Hill C.
        A graphical method for exploring heterogeneity in meta-analyses: application to a meta-analysis of 65 trials.
        Stat Med. 2002; 21: 2641-2652
        • Viechtbauer W.
        • Cheung M.W.-L.
        Outlier and influence diagnostics for meta-analysis.
        Res Synth Methods. 2010; 1: 112-125
        • Sterne J.A.C.
        • Sutton A.J.
        • Ioannidis J.P.A.
        • et al.
        Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials.
        BMJ. 2011; 343: d4002
        • Sterne J.A.
        • Egger M.
        Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis.
        J Clin Epidemiol. 2001; 54: 1046-1055
        • R Core Team. R
        A language and environment for statistical computing.
        R Foundation for Statistical Computing, Vienna, Austria2017
        • The Cochrane Collaboration
        Review manager (RevMan).
        The Nordic Cochrane Centre, Copenhagen2014
      3. Higgins J, Green S. Cochrane Handbook for systematic reviews of Interventions Version 5.1.0 [updated March 2011], The Cochrane Collaboration.

        • Nguyen L.
        • Martens J.W.M.
        • Van Hoeck A.
        • Cuppen E.
        Pan-cancer landscape of homologous recombination deficiency.
        Nat Commun. 2020; 11https://doi.org/10.1038/s41467-020-19406-4
        • Lonergan P.E.
        • Tindall D.J.
        Androgen receptor signaling in prostate cancer development and progression.
        J Carcinog. 2011; https://doi.org/10.4103/1477-3163.83937
        • Hernandez R.K.
        • Wade S.W.
        • Reich A.
        • et al.
        Incidence of bone metastases in patients with solid tumours: analysis of oncology electronic medical records in the United States.
        BMC Cancer. 2018; https://doi.org/10.1186/s12885-017-3922-0
        • Heeke A.L.
        • Pishvaian M.J.
        • Lynce F.
        • et al.
        Prevalence of homologous recombination–related gene mutations across multiple cancer types.
        JCO Precis Oncol. 2018; https://doi.org/10.1200/PO.17.00286
        • Cancer Genome Atlas Research Network
        Integrated genomic analyses of ovarian carcinoma.
        Nature. 2011; 474: 609-615
      4. Myriad Genetics, Inc. Myriad myChoice® CDx description. Available at: https://myriad.com/products-services/precision-medicine/mychoice-cdx/. 2020.

        • Foundation Medicine, Inc
        FoundationOne®CDx technical specifications.
        2018 (Available at:)
        • Postel-Vinay S.
        • Bajrami I.
        • Friboulet L.
        • et al.
        A high-throughput screen identifies PARP1/2 inhibitors as a potential therapy for ERCC1-deficient non-small cell lung cancer.
        Oncogene. 2013; 32: 5377-5387
        • Shen J.
        • Peng Y.
        • Wei L.
        • et al.
        ARID1A deficiency impairs the DNA damage checkpoint and sensitizes cells to PARP inhibitors.
        Cancer Discov. 2015; 5: 752-767
        • Gatti M.
        • Imhof R.
        • Huang Q.
        • et al.
        The ubiquitin ligase TRIP12 limits PARP1 trapping and constrains PARP inhibitor efficiency.
        Cell Rep. 2020; https://doi.org/10.1016/j.celrep.2020.107985
      5. FDA Approves Entrectinib for Tumours with NTRK Fusions - National Cancer Institute. [https://www.cancer.gov/news-events/cancer-currents-blog/2019/fda-entrectinib-ntrk-fusion]. .

      6. FDA approves pembrolizumab for first-line treatment of MSI-H/dMMR colorectal cancer. [https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-first-line-treatment-msi-hdmmr-colorectal-cancer]. .

        • Thorlund K.
        • Dron L.
        • Park J.J.H.
        • Mills E.J.
        Synthetic and external controls in clinical trials – a primer for researchers.
        Clin Epidemiol. 2020; 12: 457-467
        • Murai J.
        • Huang S.-Y.N.
        • Renaud A.
        • et al.
        Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib.
        Mol Cancer Ther. 2014; 13: 433-443
        • Pommier Y.
        • O'Connor M.J.
        • de Bono J.
        Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action.
        Sci Transl Med. 2016; 8: 362ps17
        • Jiang X.
        • Li X.
        • Li W.
        • et al.
        PARP inhibitors in ovarian cancer: sensitivity prediction and resistance mechanisms.
        J Cell Mol Med. 2019; 23: 2303-2313
        • Zafeiriou Z.
        • Bianchini D.
        • Chandler R.
        • et al.
        Genomic analysis of three metastatic prostate cancer patients with exceptional responses to carboplatin indicating different types of DNA repair deficiency.
        Eur Urol. 2019; 75: 184-192
        • Kim D.-S.
        • Camacho C.V.
        • Nagari A.
        • et al.
        Activation of PARP-1 by snoRNAs controls ribosome biogenesis and cell growth via the RNA helicase DDX21.
        Mol Cell. 2019; 75: 1270-1285.e14
        • Brenner J.C.
        • Ateeq B.
        • Li Y.
        • et al.
        Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer.
        Cancer Cell. 2011; 19: 664-678
        • Arun B.
        • Akar U.
        • Gutierrez-Barrera A.M.
        • et al.
        The PARP inhibitor AZD2281 (Olaparib) induces autophagy/mitophagy in BRCA1 and BRCA2 mutant breast cancer cells.
        Int J Oncol. 2015; 47: 262-268
        • Lee E.K.
        • Konstantinopoulos P.A.
        PARP inhibition and immune modulation: scientific rationale and perspectives for the treatment of gynecologic cancers.
        Ther Adv Med Oncol. 2020; https://doi.org/10.1177/1758835920944116
        • Chabanon R.M.
        • Soria J.-C.
        • Lord C.J.
        • Postel-Vinay S.
        Beyond DNA repair: the novel immunological potential of PARP inhibitors.
        Mol Cell Oncol. 2019; https://doi.org/10.1080/23723556.2019.1585170
        • Hodgson D.R.
        • Dougherty B.A.
        • Lai Z.
        • et al.
        Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes.
        Br J Cancer. 2018; 119: 1401-1409
        • Gay C.M.
        • Byers L.A.
        PARP inhibition combined with immune checkpoint blockade in SCLC: oasis in an immune desert or mirage?.
        J Thorac Oncol Off Publ Int Assoc Study Lung Cancer. 2019; 14: 1323-1326
        • Domchek S.M.
        • Postel-Vinay S.
        • Im S.-A.
        • et al.
        Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study.
        Lancet Oncol. 2020; 21: 1155-1164
        • Konstantinopoulos P.A.
        • Waggoner S.E.
        • Vidal G.A.
        • et al.
        TOPACIO/Keynote-162 (NCT02657889): a phase 1/2 study of niraparib + pembrolizumab in patients (pts) with advanced triple-negative breast cancer or recurrent ovarian cancer (ROC)—results from ROC cohort.
        J Clin Oncol. 2018; 36 (106–106)
        • Berlin J.A.
        • Santanna J.
        • Schmid C.H.
        • et al.
        Individual patient- versus group-level data meta-regressions for the investigation of treatment effect modifiers: ecological bias rears its ugly head.
        Stat Med. 2002; 21: 371-387
        • Tudur Smith C.
        • Clarke M.
        • Marson T.
        • et al.
        A framework for deciding if individual participant data are likely to be worthwhile. Abstracts of the 23rd Cochrane Colloquium, Vienna, Austria.
        Cochrane Database Syst Rev. 2015; 10 (RO 6.1)
        • Tierney J.F.
        • Fisher D.J.
        • Burdett S.
        • et al.
        Comparison of aggregate and individual participant data approaches to meta-analysis of randomised trials: an observational study.
        PLoS Med. 2020; 17e1003019
        • Poggio F.
        • Bruzzone M.
        • Ceppi M.
        • et al.
        Single-agent PARP inhibitors for the treatment of patients with BRCA-mutated HER2-negative metastatic breast cancer: a systematic review and meta-analysis.
        ESMO Open. 2018; 3e000361

      Linked Article