Sunitinib malate in previously untreated, nonsquamous, non-small cell lung cancer patients over the age of 70 years: Results of a Phase II trial
- 305 Downloads
Background Some elderly patients may have reduced tolerance the standard therapy (chemotherapy doublets) for stage III/IV non-small cell lung cancer (NSCLC). Sunitinib malate (S), an oral, multitargeted kinase inhibitor, shows promise as 2nd-line NSCLC treatment. This study explored the safety/efficacy of S in elderly patients with previously untreated NSCLC. Methods Primary objective: disease control rate (DCR) at six-weeks. Secondary objectives: overall response (OR, CR+PR), progression-free survival (PFS), time to progression (TTP), one-yr survival, quality of life (QOL), and safety. Treatment: S 37.5 mg daily/42-day cycle until PD or intolerable toxicity. Key inclusion: chemo-naïve stage IIIB/IV NSCLC (nonsquamous histology); ECOG PS = 0–1; ≥70 years; normal organ function. Exclusion: hemoptysis, anticoagulation, or clotting diathesis. Other standard S-specific criteria applied. Results 63 patients enrolled/60 treated. Demographics: 51 % male, 95 % white, median age 78 years (range, 70–88), 73 % ECOG = 1, 97 % Stage IV, 83 % adenocarcinoma, 44 % prior surgery, 19 % prior radiation. With a median of 2 cycles (range, 1–16), DCR = 63 %, OR = 7 % (0 CR, 4 PR). Median follow-up = 5.8 months (all; 15.9 months survivors), median PFS = 3.0 months (range, <1–25.1), median TTP = 4.5 months (range, <1–25.1), and 1-year survival = 26.4 % [95 % CI: 15.9, 38.2]. QOL declined initially, but improved over time. Treatment-related adverse events included: fatigue (48.3 %); diarrhea (38.3 %); thrombocytopenia (33.3 %), anorexia (26.7 %), mucositis (25.0 %); nausea (25.0 %), dysgeusia (20.0 %), and neutropenia (20.0 %). Conclusions The study met its primary endpoint. S produced acceptable DCR and QOL improved; however, OR was disappointing (7 %) and toxicity was greater than expected. A biomarker to identify patients more likely to benefit from S is needed.
KeywordsCommunity-based Elderly Lung cancer Survival Treatment naïve
Although this research was supported by Pfizer, Inc., (New York, NY) none of the authors had a direct or indirect commercial incentive in the conduct or analysis of this trial.
Conflict of interest statement
US Oncology Network Physicians received minimal payment associated with patient accrual to cover costs of study-specific administrative costs. Dr. Reynolds discloses stock ownership for Biogen and Idec. There are no other conflicts of interest to disclose related to the authors serving as employees, consultants or on advisory boards, stock ownership, receipt of honoraria, expert testimony, or other remuneration.
- 2.Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26(21):3543–3551, Epub 2008 May 27PubMedCrossRefGoogle Scholar
- 5.Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH, Group ECO (2008) Outcomes for elderly, advanced-stage non-small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol 26(1):60–65PubMedCrossRefGoogle Scholar
- 7.Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C (2012) Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 13(3):247–255, Epub 2012 Feb 16PubMedCrossRefGoogle Scholar
- 8.Karampeazis A, Vamvakas L, Agelidou A, Kentepozidis N, Chainis K, Chandrinos V, Vardakis N, Pallis AG, Christophyllakis C, Georgoulias V (2011) Docetaxel vs. vinorelbine in elderly patients with advanced non-small-cell lung cancer: a hellenic oncology research group randomized phase III study. Clin Lung Cancer 12(3):155–160, Epub 2011 Apr 27PubMedCrossRefGoogle Scholar
- 10.Reynolds C, Obasaju C, Schell MJ, Li X, Zheng Z, Boulware D, Caton JR, Demarco LC, O’Rourke MA, Shaw Wright G, Boehm KA, Asmar L, Bromund J, Peng G, Monberg MJ, Bepler G (2009) Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer. J Clin Oncol 27(34):5808–5815, Epub 2009 Nov 2PubMedCrossRefGoogle Scholar
- 12.Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G et al (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res Jan 9(1):327–337Google Scholar
- 14.FACT-L: For patients with Lung cancer. Available at URL: http://www.facit.org/FACITOrg/Questionnaires (accessed February 12, 2012) (FACIT.org)
- 15.FACT-G: Functional Assessment of Cancer Therapy—General. Available at URL: http://www.facit.org/FACITOrg/Questionnaires (accessed February 12, 2012)
- 16.Therasse P, Arbuck SG, Eisenhauer EA et al (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 92:205–216PubMedCrossRefGoogle Scholar
- 17.Cancer Therapy Evaluation Program. Common terminology criteria for adverse events v3.0 (CTCAE). Available at http://www.ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed June 6, 2011
- 22.Biesma B, Wymenga AN, Vincent A, Dalesio O, Smit HJ, Stigt JA, Smit EF, van Felius CL, van Putten JW, Slaets JP, Groen HJ, Dutch Chest Physician Study Group (2011) Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study. Ann Oncol 22(7):1520–1527, Epub 2011 Jan 20PubMedCrossRefGoogle Scholar