These are the first published data of QoL outcomes with nab-paclitaxel plus carboplatin treatment in patients with advanced NSCLC. In this interim analysis of the Phase III ABOUND.sqm trial, treatment with four cycles of first-line nab-paclitaxel plus carboplatin resulted in maintenance of or improvement in QoL in patients with advanced squamous NSCLC. Clinically meaningful improvements from baseline were observed in composite LCSS lung cancer pulmonary symptoms in 46% of patients. In addition, several EQ-5D-5L components stabilized or improved in the majority of patients, and approximately one third of patients reported complete resolution of a problem reported at baseline at least once during four cycles of nab-paclitaxel plus carboplatin. Improvement in QoL was more pronounced in responders compared with the overall population and nonresponders.
nab-Paclitaxel plus carboplatin is a recommended regimen for the first-line treatment of patients with both squamous and nonsquamous advanced NSCLC, based on results of the registrational Phase III trial vs paclitaxel plus carboplatin.5,6,12 In the Phase III registrational trial, significant improvements in ORR were reported for nab-paclitaxel plus carboplatin vs paclitaxel plus carboplatin for the intent-to-treat population, as well for the subset of patients with squamous histology. The regimen was well tolerated with significantly less grade ≥3 neuropathy and arthralgia but more thrombocytopenia and anemia observed compared with paclitaxel plus carboplatin.13 Additionally, significant improvements in taxane-related symptoms, such as neuropathy and neuropathic pain, were reported with nab-paclitaxel plus carboplatin compared with paclitaxel plus carboplatin, regardless of histology.14 The improvements in QoL reported during four cycles of nab-paclitaxel plus carboplatin treatment from the ABOUND.sqm study corroborate these findings and further expand the understanding of the overall clinical benefit of the nab-paclitaxel plus carboplatin regimen in patients with advanced NSCLC.12,14,18
Given the substantial symptom distress (cough, pain, loss of appetite, and hemoptysis) associated with both lung cancer and its treatment, QoL data are becoming an important tool for chemotherapy decision making.19–23 The high tumor burden in many patients with advanced NSCLC can result in a negative impact on QoL and worsen disease-related symptoms.24,25 Patients with squamous histology represent nearly one third of all patients with NSCLC; thus, analyses of QoL are of great significance, as the location, size, and cavitating nature of many squamous NSCLC tumors may increase the symptomatic burden compared with other histologies.25–27 However, there remains a lack of prospective clinical trial data of the impact of chemotherapy on symptoms/QoL, particularly for platinum-doublet therapy in patient subsets with unmet needs, such as squamous NSCLC. The current analysis adds to the limited body of knowledge on QoL data in patients with squamous NSCLC treated with first-line platinum doublets, and indicates that four cycles of nab-paclitaxel plus carboplatin treatment maintain or improve QoL in this patient population.
In addition to symptoms, patient health status (i.e., mobility, anxiety/depression, and usual activities) can be impacted by disease and treatment. For example, in a cross-sectional study of 126 newly diagnosed patients with advanced NSCLC treated with docetaxel plus cisplatin, 38% reported depression at baseline.28 QoL significantly declined with treatment in these patients, relative to those who did not report depression at baseline. In addition, depression was associated with worse survival. Another study assessed QoL changes in patients with advanced NSCLC (N = 39) and found significant declines from baseline in physical and social functioning, among other QoL areas, during treatment with platinum-doublet chemotherapy.29 In the current study evaluating nab-paclitaxel plus carboplatin treatment, some health status issues (individual EQ-5D-5L dimensions of mobility, anxiety/depression, usual activities, pain/discomfort, and self-care) were maintained or improved in the majority of patients, with ≈30% reporting complete resolution from baseline at least once during treatment.
Understanding the impact of response on QoL is also important, as tumor shrinkage associated with tumor response could alleviate symptoms that are related to tumor size.30,31 In the current study, QoL improvements measured by both the LCSS and the EQ-5D-5L were more pronounced in patients responding (CR/PR) to nab-paclitaxel plus carboplatin during the induction phase of the study vs those not responding. In line with these findings, in a retrospective analysis of patient-reported health-related QoL data from a large Phase III study in advanced NSCLC (N = 488), patients with a CR/PR or stable disease after treatment with pemetrexed or docetaxel demonstrated statistically significant mean maximum improvements from baseline in all LCSS items except for hemoptysis.30 In contrast, mean LCSS scores for each individual item worsened for patients with disease progression. Although the response data in this analysis are preliminary, they provide some insight on the clinical benefit of nab-paclitaxel plus carboplatin in patients with advanced squamous NSCLC.
EQ-5D and LCSS are validated tools for QoL measurements, yet they both have limitations that have been discussed at length elsewhere.15,16,32 Limitations of this analysis include QoL assessment only during the induction phase, the homogeneous patient subset with respect to race (mostly white), and the limited patient number in some cycles. In addition, differences in use of supportive care for the treatment of pain may have diluted the results of the EQ-5D-5L pain/discomfort category. Further analyses including data from the maintenance setting are forthcoming and may help strengthen future QoL analyses from this study.
These results from the Phase III ABOUND.sqm trial demonstrate that four cycles of first-line nab-paclitaxel plus carboplatin improved or maintained QoL in patients with advanced squamous NSCLC. In addition, patients with a tumor response (CR/PR) appeared to have better QoL outcomes than those without a response. These findings in conjunction with those reported from the Phase III registrational trial support nab-paclitaxel plus carboplatin as a treatment choice for this difficult-to-treat patient population. Moreover, it appears that declining QoL observed in nonresponders may be related to symptoms of disease progression. Therefore, given the importance of response during induction therapy, the impact of four cycles of nab-paclitaxel combination treatment on QoL in the squamous population is promising.
The authors thank Lipu Tan at Celgene for his programming work. Medical writing assistance was provided by Dena Jacob, PhD, MediTech Media, Ltd, funded by Celgene Corporation. The authors were fully responsible for all content and editorial decisions for this manuscript. This work was supported by Celgene Corporation.
MT: honoraria, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly Novartis, MSD, Roche. DRS: consulting/advisory role, Celgene; research funding, Celgene; travel, accommodations, expenses, Celgene. RMJ: nothing to disclose. MM: nothing to disclose. MAS: honoraria and speaker’s bureau, Celgene. RDP: nothing to disclose. LG: nothing to disclose. JK: consulting/advisory role: Cardinal Health; speaker’s bureau, Alexion, Celgene, Novartis. OJ: advisory or speaker, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Pierre-Fabre, Pfizer, Roche. DM: advisory board, Celgene and Bristol-Myers Squibb, speaker’s bureau, Genentech. DI: nothing to disclose. ESK: grant/research support, Celgene. HW: consultant/advisor and honoraria, AstraZeneca, Boehringer-Ingelheim, BristolMyersSquibb, Celgene, Genentech/Roche; Merck, Spectrum, Takeda; Speaker: BMS, Genentech/Roche. AK, NT, TJO: employment or leadership position and stock ownership, Celgene Corporation. CG: nothing to disclose.
Michael Thomas,1,2 David R Spigel,3 Robert M. Jotte,4 Michael McCleod,5 Mark A. Socinski,6 Ray D. Page,7 Laurent Gressot,8 Jeanna Knoble,9 Oscar Juan,10 Daniel Morgensztern,11 Dolores Isla,12 Edward S. Kim,13 Howard West,14 Amy Ko,15 Teng Jin Ong,15 Nataliya Trunova,15 Cesare Gridelli16
On behalf of ABOUND.sqm investigators
1Department of Thoracic Oncology/Internal Medicine, Thoraxklinik im Universitätsklinikum Heidelberg, 2Translational Lung Research Center Heidelberg, Heidelberg, Germany; 3Sarah Cannon Research Institute, Nashville, TN, 4Department of Medical Oncology/Hematology, Rocky Mountain Cancer Centers, Denver, CO, 5Florida Cancer Specialists, Fort Myers, 6Florida Hospital Cancer Institute, Orlando, FL, 7The Center for Cancer and Blood Disorders, Fort Worth, 8North Cypress Cancer Center, Cypress, TX, 9The Mark H. Zangmeister Center, Columbus, OH, USA; 10Department of Medical Oncology, Hospital Universitari i Politécnic La Fe, Valencia, Spain; 11Department of Medical Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; 12Department of Medical Oncology, University Hospital Lozano Blesa, Zaragoza, Spain; 13Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, 14Thoracic Oncology Program, Swedish Cancer Institute, Seattle, WA, 15Celgene Corporation, Summit, NJ, USA; 16Department of Oncology/Hematology, S.G. Moscati Hospital, Avellino, Italy
1. Akin S, Can G, Aydiner A, Ozdilli K, Durna Z. Quality of life, symptom experience and distress of lung cancer patients undergoing chemotherapy. Eur J Oncol Nurs. 2010;14(5):400–409.
2. Larsson M, Ljung L, Johansson BB. Health-related quality of life in advanced non-small cell lung cancer: Correlates and comparisons to normative data. Eur J Cancer Care (Engl). 2012;21(5):642–649.
3. Hirsh V. Are the data on quality of life and patient reported outcomes from clinical trials of metastatic non-small-cell lung cancer important? World J Clin Oncol. 2013;4(4):82–84.
4. Iyer S, Roughley A, Rider A, Taylor-Stokes G. The symptom burden of non-small cell lung cancer in the USA: A real-world cross-sectional study. Support Care Cancer. 2014;22(1):181–187.
5. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. V3. Fort Washington, PA, USA: National Comprehensive Cancer Network; 2017.
6. Novello S, Barlesi F, Califano R, et al. Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27 (Suppl 5):v1–V27.
7. Avelino CU, Cardoso RM, Aguiar SS, Silva MJ. Assessment of quality of life in patients with advanced non-small cell lung carcinoma treated with a combination of carboplatin and paclitaxel. J Bras Pneumol. 2015;41(2):133–142.
8. Geater SL, Xu CR, Zhou C, et al. Symptom and quality of life improvement in LUX-lung 6: an open-label phase III study of afatinib versus cisplatin/gemcitabine in Asian patients with EGFR mutation-positive advanced non-small-cell lung cancer. J Thorac Oncol. 2015;10(6):883–889.
9. Boye M, Wang X, Srimuninnimit V, et al. First-line pemetrexed plus cisplatin followed by gefitinib maintenance therapy versus gefitinib monotherapy in East Asian never-smoker patients with locally advanced or metastatic nonsquamous non-small-cell lung cancer: quality of life results from a randomized phase III trial. Clin Lung Cancer. 2016;17(2):150–160.
10. Yang JC, Hirsh V, Schuler M, et al. Symptom control and quality of life in LUX-lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3342–3350.
11. Abraxane for injectable suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) [prescribing information]: Summit, NJ: Celgene Corporation; 2015.
12. Socinski MA, Bondarenko I, Karaseva NA, et al. 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. 2012;30(17):2055–2062.
13. Socinski MA, Langer CJ, Okamoto I, et al. Safety and efficacy of weekly nab®-paclitaxel in combination with carboplatin as first-line therapy in elderly patients with advanced non-small-cell lung cancer. Ann Oncol. 2013;24(2):314–321.
14. Hirsh V, Okamoto I, Hon JK, et al. 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. 2014;9(1):83–90.
15. Hollen PJ, Gralla RJ, Kris MG, et al. Measurement of quality of life in patients with lung cancer in multicenter trials of new therapies. Psychometric assessment of the Lung Cancer Symptom Scale. Cancer. 1994;73(8):2087–2098.
16. Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727–1736.
17. euroqol.org [homepage on the Internet]. EuroQol. EQ-5D. EuroQol; 2016. Available from: www.euroqol.org. Accessed: August 31, 2017.
18. Braun DP, Gupta D, Staren ED. Quality of life assessment as a predictor of survival in non-small cell lung cancer. BMC Cancer. 2011;11:353.
19. Hollen PJ, Gralla RJ, Kris MG, Eberly SW, Cox C. Normative data and trends in quality of life from the Lung Cancer Symptom Scale (LCSS). Support Care Cancer. 1999;7(3):140–148.
20. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010; 363(8):733–742.
21. Temel JS, Pirl WF, Lynch TJ. Comprehensive symptom management in patients with advanced-stage non-small-cell lung cancer. Clin Lung Cancer. 2006;7(4):241–249.
22. Smith EL, Hann DM, Ahles TA, et al. Dyspnea, anxiety, body consciousness, and quality of life in patients with lung cancer. J Pain Symptom Manage. 2001;21(4):323–329.
23. US Department of Health and Human Services, US Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for industry: clinical trial endpoints for the approval of cancer drugs and biologics. FDA; 2007. Available from: http://www.fda.gov/downloads/Drugs/…/Guidances/ucm071590.pdf. Accessed: August 31, 2017.
24. Geiger C, Chen Z, Zhang C, et al. Investigating the correlation between disease burden and symptoms in patients with advanced stage lung cancer. J Clin Oncol. 2015;33 Suppl: abstract e19057.
25. Nichols L, Saunders R, Knollmann FD. Causes of death of patients with lung cancer. Arch Pathol Lab Med. 2012;136(12):1552–1557.
26. Drilon A, Rekhtman N, Ladanyi M, Paik P. Squamous-cell carcinomas of the lung: emerging biology, controversies, and the promise of targeted therapy. Lancet Oncol. 2012;13(10):e418–e426.
27. Scagliotti GV, Novello S, Rapetti S, Papotti M. Current state-of-the-art therapy for advanced squamous cell lung cancer. Am Soc Clin Oncol Educ Book. 2013:354–358.
28. Chen J, Li W, Cui L, et al. Chemotherapeutic response and prognosis among lung cancer patients with and without depression. J Cancer. 2015;6(11):1121–1129.
29. Arraras JI, Hernandez B, Martinez M, et al. Quality of life in Spanish advanced non-small-cell lung cancer patients: determinants of global QL and survival analyses. Springerplus. 2016;5(1):836.
30. de Marinis F, Pereira JR, Fossella F, et al. Lung Cancer Symptom Scale outcomes in relation to standard efficacy measures: an analysis of the phase III study of pemetrexed versus docetaxel in advanced non-small cell lung cancer. J Thorac Oncol. 2008;3(1):30–36.
31. Wu YL, Fukuoka M, Mok TS, et al. Tumor response and health-related quality of life in clinically selected patients from asia with advanced non-small-cell lung cancer treated with first-line gefitinib: post hoc analyses from the IPASS study. Lung Cancer. 2013;81(2):280–287.
32. Oppe M, Devlin NJ, van Hout B, Krabbe PF, de Charro F. A program of methodological research to arrive at the new international EQ-5D-5L valuation protocol. Value Health. 2014;17(4):445–453.
Source: Lung Cancer: Targets and Therapy.
Originally published October 30, 2017.