Survival, quality-adjusted survival, and other clinical end points in older advanced non-small-cell lung cancer patients treated with albumin-bound paclitaxel

C J Langer, V Hirsh, I Okamoto, F-J Lin, Y Wan, S Whiting, T J Ong, M F Renschler, M F Botteman, C J Langer, V Hirsh, I Okamoto, F-J Lin, Y Wan, S Whiting, T J Ong, M F Renschler, M F Botteman

Abstract

Background: This analysis compared the quality-adjusted survival and clinical outcomes of albumin-bound paclitaxel+carboplatin (nab-PC) vs solvent-based paclitaxel+carboplatin (sb-PC) as first-line therapy in advanced non-small-cell lung cancer (NSCLC) in older patients.

Methods: Using age-based subgroup data from a randomised Phase-3 clinical trial, nab-PC and sb-PC were compared with respect to overall response rate (ORR), overall survival (OS), progression-free survival (PFS), quality of life (QoL), safety/toxicity, and quality-adjusted time without symptoms or toxicity (Q-TWiST) with ages ⩾60 and ⩾70 years as cut points.

Results: Among patients aged ⩾60 years (N=546), nab-PC (N=265) significantly increased ORR and prolonged OS, despite a non-significant improvement in PFS, vs sb-PC (N=281). Nab-PC improved QoL and was associated with less neuropathy, arthralgia, and myalgia but resulted in more anaemia and thrombocytopenia. Nab-PC yielded significant Q-TWiST benefits (11.1 vs 9.8 months; 95% CI of gain: 0.2-2.6), with a relative Q-TWiST gain of 10.8% (ranging from 6.4% to 15.1% in threshold analysis). In the ⩾70 years age group, nab-PC showed similar, but non-significant, ORR, PFS, and Q-TWiST benefits and significantly improved OS and QoL.

Conclusion: Nab-PC as first-line therapy in older patients with advanced NSCLC increased ORR, OS, and QoL and resulted in quality-adjusted survival gains compared with standard sb-PC.

Conflict of interest statement

CJL received honorarium/consulting fee and has served as an advisor for Celgene Corporation. VH is a consultant for Celgene Corporation. F-JL, YW, and MFB are employees, and MFB is also a shareholderof Pharmerit International, an independent contract research organisation that received research funding from Celgene Corporation. SW, TJO, and MFR are employees of Celgene Corporation. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Composite change from baseline for the 16-item FACT-Taxane. Symptoms were reported prior to dosing on day 1 of each cycle. Note that larger bars represent greater deteriorations from baseline as perceived by patients. Composite change (A) in patients aged ⩾60 years and (B) in patients aged ⩾70 years. BL, baseline; nab-PC, nab-paclitaxel+carboplatin; sb-PC, solvent-based paclitaxel+carboplatin.
Figure 2
Figure 2
Partitioned survival plots showing the mean times in TOX, TWiST, and REL states. The area under TOX curves represents the mean time in TOX state. The difference in area under PFS and TOX curves represent the mean time in TWiST state. The difference in area under OS and PFS curves represents the mean time in REL state. Partitioned survival plots (A) in patients aged ⩾60 years and (B) in patients aged ⩾70 years. nab-PC, nab-paclitaxel+carboplatin; OS, overall survival; PFS, progression-free survival; sb-PC, solvent-based paclitaxel+carboplatin; TOX, toxicity with adverse event grade ⩾3.
Figure 3
Figure 3
Utility threshold plot through 24 months of follow-up. In these plots, the utility of TWiST was fixed at 1, and the utility for toxicity (UTOX) and utility for time after disease progression (UREL) both varied from 0 to 1. The base-case scenario (UTOX=UREL=0.5) was marked with a white dot. The diagonal bands of different shading indicate the magnitude of absolute Q-TWiST gain from nab-PC (vs sb-PC). The grid-shaded area indicates pairs of utility weights with statistically significant (P<0.05) Q-TWiST differences in favour of nab-PC. (A) Patients with an age ⩾60 years; (B) patients with an age ⩾70 years.
Figure 4
Figure 4
Differences in the Q-TWiST at various follow-up durations. Differences in the Q-TWiST (A) in patients aged ⩾60 years and (B) in patients aged ⩾70 years. Note: The solid circle sign represents significant difference in Q-TWiST (P<0.05) and the hollow circle sign represents non-significant difference in Q-TWiST.

References

    1. Authier N, Gillet JP, Fialip J, Eschalier A, Coudore F (2000) Description of a short-term Taxol-induced nociceptive neuropathy in rats. Brain Res 887(2): 239–249.
    1. Cella D, Peterman A, Hudgens S, Webster K, Socinski MA (2003) Measuring the side effects of taxane therapy in oncology: the functional assesment of cancer therapy-taxane (FACT-taxane). Cancer 98(4): 822–831.
    1. Chen N, Li Y, Ye Y, Palmisano M, Chopra R, Zhou S (2014) Pharmacokinetics and pharmacodynamics of nab-paclitaxel in patients with solid tumors: disposition kinetics and pharmacology distinct from solvent-based paclitaxel. J Clin Pharmacol 54(10): 1097–1107.
    1. Chouaid C, Agulnik J, Goker E, Herder GJ, Lester JF, Vansteenkiste J, Finnern HW, Lungershausen J, Eriksson J, Kim K, Mitchell PL (2013) Health-related quality of life and utility in patients with advanced non-small-cell lung cancer: a prospective cross-sectional patient survey in a real-world setting. J Thorac Oncol 8(8): 997–1003.
    1. Corey-Lisle PK, Peck R, Mukhopadhyay P, Orsini L, Safikhani S, Bell JA, Hortobagyi G, Roche H, Conte P, Revicki DA (2012) Q-TWiST analysis of ixabepilone in combination with capecitabine on quality of life in patients with metastatic breast cancer. Cancer 118(2): 461–468.
    1. Davidoff AJ, Tang M, Seal B, Edelman MJ (2010) Chemotherapy and survival benefit in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 28(13): 2191–2197.
    1. Dijkman B, Kooistra B, Bhandari M Evidence-Based Surgery Working Group (2009) How to work with a subgroup analysis. Can J Surg 52(6): 515–522.
    1. Ettinger DS, Akerley W, Borghaei H, Chang AC, Cheney RT, Chirieac LR, D'Amico TA, Demmy TL, Ganti AK, Govindan R, Grannis FW Jr., Horn L, Jahan TM, Jahanzeb M, Kessinger A, Komaki R, Kong FM, Kris MG, Krug LM, Lennes IT, Loo BW Jr., Martins R, O'Malley J, Osarogiagbon RU, Otterson GA, Patel JD, Pinder-Schenck MC, Pisters KM, Reckamp K, Riely GJ, Rohren E, Swanson SJ, Wood DE, Yang SC, Hughes M, Gregory KM Nccn (2012) Non-small cell lung cancer. J Natl Compr Canc Netw 10(10): 1236–1271.
    1. Gelber RD, Goldhirsch A, Cole BF (1993) Evaluation of effectiveness: Q-TWiST. The International Breast Cancer Study Group. Cancer Treat Rev 19(Suppl A): 73–84.
    1. Goldhirsch A, Gelber RD, Simes RJ, Glasziou P, Coates AS (1989) Costs and benefits of adjuvant therapy in breast cancer: a quality-adjusted survival analysis. J Clin Oncol 7(1): 36–44.
    1. Hardy D, Liu CC, Xia R, Cormier JN, Chan W, White A, Burau K, Du XL (2009) Racial disparities and treatment trends in a large cohort of elderly black and white patients with nonsmall cell lung cancer. Cancer 115(10): 2199–2211.
    1. Hirsh V, Okamoto I, Hon JK, Page RD, Orsini J, Sakai H, Zhang H, Renschler MF, Socinski MA (2014) Patient-reported neuropathy and taxane-associated symptoms in a phase 3 trial of nab-paclitaxel plus carboplatin versus solvent-based paclitaxel plus carboplatin for advanced non-small-cell lung cancer. J Thorac Oncol 9(1): 83–90.
    1. Jang RW, Le Maitre A, Ding K, Winton T, Bezjak A, Seymour L, Shepherd FA, Leighl NB (2009) Quality-adjusted time without symptoms or toxicity analysis of adjuvant chemotherapy in non-small-cell lung cancer: an analysis of the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial. J Clin Oncol 27(26): 4268–4273.
    1. Jatoi A, Hillman S, Stella P, Green E, Adjei A, Nair S, Perez E, Amin B, Schild SE, Castillo R, Jett JR North Central Cancer Treatment Group (2005) Should elderly non-small-cell lung cancer patients be offered elderly-specific trials? Results of a pooled analysis from the North Central Cancer Treatment Group. J Clin Oncol 23(36): 9113–9119.
    1. Kratz F (2008) Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release 132(3): 171–183.
    1. Langer CJ (2011) Clinical evidence on the undertreatment of older and poor performance patients who have advanced non-small-cell lung cancer: is there a role for targeted therapy in these cohorts? Clin Lung Cancer 12(5): 272–279.
    1. Lichtman SM, Wildiers H, Chatelut E, Steer C, Budman D, Morrison VA, Tranchand B, Shapira I, Aapro M International Society of Geriatric Oncology Chemotherapy Taskforce (2007) International Society of Geriatric Oncology Chemotherapy Taskforce: evaluation of chemotherapy in older patients—an analysis of the medical literature. J Clin Oncol 25(14): 1832–1843.
    1. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA (2008) Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 83(5): 584–594.
    1. Nafees B, Stafford M, Gavriel S, Bhalla S, Watkins J (2008) Health state utilities for non small cell lung cancer. Health Qual Life Outcomes 6: 84.
    1. Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E Group EGW (2012) Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7): vii56–vii64.
    1. Qi WX, Tang LN, He AN, Shen Z, Lin F, Yao Y (2012) Doublet versus single cytotoxic agent as first-line treatment for elderly patients with advanced non-small-cell lung cancer: a systematic review and meta-analysis. Lung 190(5): 477–485.
    1. Quoix E (2011) Optimal pharmacotherapeutic strategies for elderly patients with advanced non-small cell lung cancer. Drugs Aging 28(11): 885–894.
    1. Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavole A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducolone A, Lebitasy MP, Baudrin L, Laporte S, Milleron B Intergroupe Francophone de Cancerologie Thoracique (2011) Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet 378(9796): 1079–1088.
    1. Reni M, Wan Y, Solem C, Whiting S, Ji X, Botteman M (2014) Quality-adjusted survival with combination nab-paclitaxel+gemcitabine vs gemcitabine alone in metastatic pancreatic cancer: a Q-TWiST analysis. J Med Econ 17(5): 338–346.
    1. Revicki DA, Feeny D, Hunt TL, Cole BF (2006) Analyzing oncology clinical trial data using the Q-TWiST method: clinical importance and sources for health state preference data. Qual Life Res 15(3): 411–423.
    1. Rizvi NA, Riely GJ, Azzoli CG, Miller VA, Ng KK, Fiore J, Chia G, Brower M, Heelan R, Hawkins MJ, Kris MG (2008) Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer. J Clin Oncol 26(4): 639–643.
    1. Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O'Rourke M, Levitan N, Gressot L, Vincent M, Burkes R, Coughlin S, Kim Y, Berille J (2000) Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 18(10): 2095–2103.
    1. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L National Cancer Institute of Canada Clinical Trials Group (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353(2): 123–132.
    1. Sherrill B, Sherif B, Amonkar MM, Maltzman J, O'Rourke L, Johnston S (2011) Quality-adjusted survival analysis of first-line treatment of hormone-receptor-positive HER2+ metastatic breast cancer with letrozole alone or in combination with lapatinib. Curr Med Res Opin 27(12): 2245–2252.
    1. Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF (2012) Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol 30(17): 2055–2062.
    1. Socinski MA, Evans T, Gettinger S, Hensing TA, Sequist LV, Ireland B, Stinchcombe TE (2013. a) Treatment of stage IV non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 143(5 Suppl): e341S–e3468.
    1. Socinski MA, Langer CJ, Okamoto I, Hon JK, Hirsh V, Dakhil SR, Page RD, Orsini J, Zhang H, Renschler MF (2013. b) Safety and efficacy of weekly nab(R)-paclitaxel in combination with carboplatin as first-line therapy in elderly patients with advanced non-small-cell lung cancer. Ann Oncol 24(2): 314–321.
    1. Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, Yablonsky PK, Bhar P, Iglesias J (2010) A dose finding study of weekly and every-3-week nab-Paclitaxel followed by carboplatin as first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol 5(6): 852–861.
    1. Sparreboom A, Scripture CD, Trieu V, Williams PJ, De T, Yang A, Beals B, Figg WD, Hawkins M, Desai N (2005) Comparative preclinical and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol). Clin Cancer Res 11(11): 4136–4143.
    1. Tas F, Ciftci R, Kilic L, Karabulut S (2013) Age is a prognostic factor affecting survival in lung cancer patients. Oncol Lett 6(5): 1507–1513.
    1. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3): 205–216.
    1. Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, Langer C, Murphy B, Cumberlin R, Coleman CN, Rubin P (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13(3): 176–181.
    1. Wildiers H, Mauer M, Pallis A, Hurria A, Mohile SG, Luciani A, Curigliano G, Extermann M, Lichtman SM, Ballman K, Cohen HJ, Muss H, Wedding U (2013) End points and trial design in geriatric oncology research: a joint European organisation for research and treatment of cancer—Alliance for Clinical Trials in Oncology—International Society Of Geriatric Oncology position article. J Clin Oncol 31(29): 3711–3718.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅