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Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1

Published:October 29, 2022DOI:https://doi.org/10.1016/j.ejca.2022.09.029

      Highlights

      • This Q-TWiST analysis assessed quality-adjusted survival in patients with mTNBC.
      • Pembrolizumab showed a significant Q-TWiST benefit in PD-L1–positive mTNBC.
      • The benefits continued to accrue with longer follow-up time.
      • Pembrolizumab demonstrated a favourable benefit-risk profile in this population.

      Abstract

      Objective

      In the KEYNOTE-355 (KN355) trial, pembrolizumab in combination with chemotherapy demonstrated superior efficacy and manageable safety compared with chemotherapy alone in patients with previously untreated locally recurrent inoperable and metastatic triple-negative breast cancer (mTNBC) with PD-L1 positive (Combined Positive Score [CPS]≥ 10) tumours. This study aimed to evaluate the clinical benefits and risks of pembrolizumab measured by quality-adjusted survival in the trial population.

      Methods

      The study used data from the final analysis of KN355. The Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) analysis was used to compare treatments of pembrolizumab plus chemotherapy versus chemotherapy alone. Patients’ survival time was partitioned into three health states — toxicity before disease progression (TOX), time without symptoms or toxicity before disease progression (TWiST), and relapse (REL). Utilities for these health states were estimated using EuroQol-5 Dimensions, 3 Levels (EQ-5D-3L) data collected in KN355. Q-TWiST was derived as the utility-weighted sum of the mean health state durations.

      Results

      Patients randomised to pembrolizumab plus chemotherapy had 3.7 months greater Q-TWiST (relative gain of 18%; P = 0.003) compared to those randomised to chemotherapy at the median follow-up of 44 months, and 4.3 months greater Q-TWiST (relative gain of 20%; P = 0.004) at the maximum follow-up of 52 months. The Q-TWiST gain increased with longer follow-up time.

      Conclusions

      Pembrolizumab plus chemotherapy was associated with statistically significant and clinically important improvement in Q-TWiST compared to chemotherapy in previously untreated PD-L1–positive mTNBC.

      Keywords

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      References

        • Plasilova M.L.
        • Hayse B.
        • Killelea B.K.
        • Horowitz N.R.
        • Chagpar A.B.
        • Lannin D.R.
        Features of triple-negative breast cancer: analysis of 38,813 cases from the national cancer database.
        Medicine (Baltim). Aug 2016; 95e4614https://doi.org/10.1097/md.0000000000004614
        • Dent R.
        • Hanna W.M.
        • Trudeau M.
        • Rawlinson E.
        • Sun P.
        • Narod S.A.
        Pattern of metastatic spread in triple-negative breast cancer.
        Breast Cancer Res Treat. May 2009; 115: 423-428https://doi.org/10.1007/s10549-008-0086-2
        • Kassam F.
        • Enright K.
        • Dent R.
        • et al.
        Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design.
        Clin Breast Cancer. Feb 2009; 9: 29-33https://doi.org/10.3816/CBC.2009.n.005
        • Bergin A.R.T.
        • Loi S.
        Triple-negative breast cancer: recent treatment advances.
        F1000Res. 2019; 8https://doi.org/10.12688/f1000research.18888.1
        • Kwapisz D.
        Pembrolizumab and atezolizumab in triple-negative breast cancer.
        Cancer Immunol Immunother. Mar 2021; 70: 607-617https://doi.org/10.1007/s00262-020-02736-z
      1. US Food and Drug Administration. Pembrolizumab product label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125514s088lbl.pdf. [Accessed 10 March 2022].

      2. European Medicines Agency. Pembrolizumab product label. https://www.ema.europa.eu/en/documents/product-information/keytruda-epar-product-information_en.pdf. [Accessed 10 March 2022].

        • Cortes J.
        • Cescon D.W.
        • Rugo H.S.
        • et al.
        Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial.
        Lancet. Dec 5 2020; 396: 1817-1828https://doi.org/10.1016/s0140-6736(20)32531-9
        • Cortes J.
        • Rugo H.S.
        • Cescon D.W.
        • et al.
        KEYNOTE-355 investigators. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer.
        N Engl J Med. 2022 Jul 21; 387: 217-226https://doi.org/10.1056/NEJMoa2202809
        • Shrestha A.
        • Martin C.
        • Burton M.
        • Walters S.
        • Collins K.
        • Wyld L.
        Quality of life versus length of life considerations in cancer patients: a systematic literature review.
        Psychooncology. Jul 2019; 28: 1367-1380https://doi.org/10.1002/pon.5054
      3. US Food and Drug Administration. Plan for issuance of patient-focused drug development guidance under 21st century cures act title III section 3002. https://www.fda.gov/files/about%20fda/published/Plan-for-Issuance-of-Patient%E2%80%90Focused-Drug-Development-Guidance.pdf. [Accessed 10 March 2022].

      4. European Medicines Agency. Revised framework for interaction between the European Medicines Agency and patients and consumers and their organisations. https://www.ema.europa.eu/en/documents/other/engagement-framework-european-medicines-agency-patients-consumers-their-organisations_en.pdf. [Accessed 10 March 2022].

        • Schnipper L.E.
        • Davidson N.E.
        • Wollins D.S.
        • et al.
        Updating the American Society of clinical oncology value framework: revisions and reflections in response to comments received.
        J Clin Oncol. Aug 20 2016; 34: 2925-2934https://doi.org/10.1200/JCO.2016.68.2518
        • Mt-Isa S.
        • Hallgreen C.E.
        • Wang N.
        • Callréus T.
        • Genov G.
        • Hirsch I.
        • et al.
        Balancing benefit and risk of medicines: a systematic review and classification of available methodologies.
        Pharmacoepidemiol Drug Saf. 2014; 23: 667-678
        • Gelber R.D.
        • Goldhirsch A.
        A new endpoint for the assessment of adjuvant therapy in postmenopausal women with operable breast cancer.
        J Clin Oncol. Dec 1986; 4: 1772-1779https://doi.org/10.1200/jco.1986.4.12.1772
        • Gelber R.D.
        • Goldhirsch A.
        • Cavalli F.
        Quality-of-life-adjusted evaluation of adjuvant therapies for operable breast cancer. The International Breast Cancer Study Group.
        Ann Intern Med. Apr 15 1991; 114: 621-628https://doi.org/10.7326/0003-4819-114-8-621
        • Goldhirsch A.
        • Gelber R.D.
        • Simes R.J.
        • Glasziou P.
        • Coates A.S.
        Costs and benefits of adjuvant therapy in breast cancer: a quality-adjusted survival analysis.
        J Clin Oncol. Jan 1989; 7: 36-44https://doi.org/10.1200/jco.1989.7.1.36
        • Tate W.R.
        • Skrepnek G.H.
        Quality-adjusted time without symptoms or toxicity (Q-TWiST): patient-reported outcome or mathematical model? A systematic review in cancer.
        Psychooncology. Mar 2015; 24: 253-261https://doi.org/10.1002/pon.3595
        • Solem C.T.
        • Kwon Y.
        • Shah R.M.
        • Aly A.
        • Botteman M.F.
        Systematic review and benchmarking of quality-adjusted time without symptoms or toxicity (Q-TWiST) in oncology.
        Expert Rev Pharmacoecon Outcomes Res. Jun 2018; 18: 245-253https://doi.org/10.1080/14737167.2018.1434414
        • Shah R.
        • Botteman M.
        • Solem C.T.
        • et al.
        A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of nivolumab versus everolimus in advanced renal cell carcinoma (aRCC).
        Clin Genitourin Cancer. Oct 2019; 17 (e1): 356-365https://doi.org/10.1016/j.clgc.2019.05.010
        • Huang M.
        • Pietanza M.C.
        • Samkari A.
        • et al.
        Q-TWiST analysis to assess benefit-risk of pembrolizumab in patients with PD-L1-positive advanced or metastatic non-small cell lung cancer.
        Pharmacoeconomics. Jan 2019; 37: 105-116https://doi.org/10.1007/s40273-018-0752-0
        • McDermott D.F.
        • Shah R.
        • Gupte-Singh K.
        • et al.
        Quality-adjusted survival of nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone among treatment-naive patients with advanced melanoma: a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis.
        Qual Life Res. Jan 2019; 28: 109-119https://doi.org/10.1007/s11136-018-1984-3
        • Cocks K.
        • Contente M.
        • Simpson S.
        • DeRosa M.
        • Taylor F.C.
        • Shaw J.W.
        A Q-TWiST analysis comparing nivolumab and therapy of investigator's choice in patients with recurrent/metastatic platinum-refractory squamous cell carcinoma of the head and neck.
        Pharmacoeconomics. Aug 2019; 37: 1041-1047https://doi.org/10.1007/s40273-019-00798-1
        • Huang M.
        • Haiderali A.
        • Hu P.
        • Mitashri C.
        • Pan W.
        HSR22-146: health utility in patients with previously untreated locally recurrent inoperable or metastatic TNBC.
        J Natl Compr Canc Netw. 31 Mar 2022 2022; 20 (HSR22-146): HSR22-HSR146https://doi.org/10.6004/jnccn.2021.7148
        • Eisenhauer E.A.
        • Therasse P.
        • Bogaerts J.
        • et al.
        New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).
        Eur J Cancer. Jan 2009; 45: 228-247https://doi.org/10.1016/j.ejca.2008.10.026
      5. Common Terminology Criteria for Adverse Events V4.03. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_40. [Accessed 4 April 2022].

        • Shaw J.W.
        • Johnson J.A.
        • Coons S.J.
        US valuation of the EQ-5D health states: development and testing of the D1 valuation model.
        Med Care. Mar 2005; 43: 203-220https://doi.org/10.1097/00005650-200503000-00003
        • Glasziou P.P.
        • Simes R.J.
        • Gelber R.D.
        Quality adjusted survival analysis.
        Stat Med. Nov 1990; 9: 1259-1276https://doi.org/10.1002/sim.4780091106
        • Revicki D.A.
        • Feeny D.
        • Hunt T.L.
        • Cole B.F.
        Analyzing oncology clinical trial data using the Q-TWiST method: clinical importance and sources for health state preference data.
        Qual Life Res. Apr 2006; 15: 411-423https://doi.org/10.1007/s11136-005-1579-7
        • Nooij M.A.
        • de Haes J.C.
        • Beex L.V.
        • et al.
        Continuing chemotherapy or not after the induction treatment in advanced breast cancer patients. clinical outcomes and oncologists' preferences.
        Eur J Cancer. Mar 2003; 39: 614-621https://doi.org/10.1016/s0959-8049(02)00869-9
        • Sherrill B.
        • Amonkar M.M.
        • Stein S.
        • Walker M.
        • Geyer C.
        • Cameron D.
        Q-TWiST analysis of lapatinib combined with capecitabine for the treatment of metastatic breast cancer.
        Br J Cancer. Sep 2 2008; 99: 711-715https://doi.org/10.1038/sj.bjc.6604501
        • Corey-Lisle P.K.
        • Peck R.
        • Mukhopadhyay P.
        • et al.
        Q-TWiST analysis of ixabepilone in combination with capecitabine on quality of life in patients with metastatic breast cancer.
        Cancer. Jan 15 2012; 118: 461-468https://doi.org/10.1002/cncr.26213
        • Cortes J.
        • Pérez-García J.
        • Whiting S.
        • et al.
        Quality-adjusted survival with nab-paclitaxel versus standard paclitaxel in metastatic breast cancer: a Q-TWiST analysis.
        Clin Breast Cancer. Oct 2018; 18: e919-e926https://doi.org/10.1016/j.clbc.2018.03.014
        • Irish W.
        • Sherrill B.
        • Cole B.
        • Gard C.
        • Glendenning G.A.
        • Mouridsen H.
        Quality-adjusted survival in a crossover trial of letrozole versus tamoxifen in postmenopausal women with advanced breast cancer.
        Ann Oncol. Sep 2005; 16: 1458-1462https://doi.org/10.1093/annonc/mdi275