Twenty-Two Years of Phase III Trials for Patients With
`Advanced Non—Small—Cell Lung Cancer: Sobering Results
`
`By Oscar S. Breathnach, Boris Freidlin, Barbara Conley, Mark R. Green, David H. Johnson, David R. Ganclara,
`Michael O'Connell, Frances A, Shepherd, and Bruce E. Johnson
`
`fig-pgg: To determine the changes in clinical trials
`and outcomes of patients with advanced-stage non-
`small-cell lung cancer (NSCLC) treated on phase III ran-
`domized trials initiated in North America from ‘I973 to
`‘I 994.
`
`fgt_it_eg_§___a:_1_d' Methods: Phase III trials for patients
`with advanced-stage NSCLC were identified through a
`search of the National Cancer lnstitute’s Cancer Ther-
`apy Evaluation Program database from 1973 to 1994,
`contact with Cooperative Groups, and by literature
`search of MEDLINE. Patients with advanced NSCLC
`
`treated during a similar time interval were also exam-
`ined in the SEER database. Trends were tested in the
`number of trials, in the number and sex of patients
`entered on the trials, and in survival over time.
`Results: Thirty-three phase III trials were initiated
`between 1973 and ‘I994. Twenty-tour trials (73%)
`were initiated within the first half of this period (‘I 973 to
`
`YSTEMIC CHEMOTHERAPY for patients with ad-
`vanced—stage non—small—cell
`lung cancer
`tNSCLC)
`prolongs survival and palliates symptoms compared with
`best supportive care alone.1'2 Meta-analysis of patients with
`advanced NSCLC who were treated with cisplatin-based
`therapy shows a modest improvement in survival.‘ Despite
`systemic chemotherapy,
`lung cancer remains the greatest
`cause of cancer-related mortality within the United Suites.3
`The 5-year survival of patients with advanced-stage NSCLC
`is less than 5%.
`
`From the Lowe Center fix‘ Thoracic Oiicology, Department of/lditlt
`Oncology, Dana-Farber Ccmcer lnrtitrite. and Departmeirls of Medi-
`cine. Brigliam arid Women's Hospital arid Hur'vard A/Iedicul Sc/tool.
`Boston, MA; Biometric Research Branch. Clinical Investigations
`Branch. Cancer Therapy Evaluation Program, Division of Cancer
`Treaimem and Diagnosis. National Cancer Institute, Betliesda, It/AD;
`Cancer and Lxziikemia Group B. CIiicago. IL: Easterii Cooperative
`Oncologv Group. Pittsbwgli. PA.’ Southwest Oncology Group. San
`Antonio, TX: Nortli Central Cancer Treatment Group Philadelpliia.
`PA; and National Cancer Iristitiite M Caricida Clinical Trials Group.
`Kingslart. Ontario, Canada.
`Submitted June 30, 2000; accepted November 20, 2000.
`Address reprint requests to Oscar S. Breatlmacli, MD, Thoracic
`Oncology Program, Di7m'i—F'nrbei‘ Cancer Insriiitte. Ste I234, 44
`Biriney St, Boston, }v!A 02115.
`© 2001 by/lmerican Society ofClinical Oncology.
`0732-183 '/(}.l/1906-173-i’
`
`1983) and accounted for 5,359 (64‘'/.) of the 8,434
`eligible patients. The median number of patients
`treated per arm of the trials rose from 77 (I973 to
`1933) to 121 (1984 to 1994) (P < .0013. Five trials (1 5%)
`showed a statistically significant difference in survival
`between treatment arms, with a median prolongation
`of the median survival of 2 months (range, 0.7 to 2.7
`months).
`Conclusion: Analysis of past trials in North America
`shows that the prolongation in median survival be-
`tween two arms of a randomized study was rarely in
`excess of 2 months. Techniques for improved use of
`patient resources and appropriate trial design for
`phase III randomized therapeutic trials with patients
`with advanced NSCLC need to be developed.
`J Clin Oncal
`l9:l734-l742. 0 20!” by American
`Society of Clinical Oncology.
`
`trials for patients with
`Prior analysis of phase III
`extensive—stage small—cell lung cancer (SCLC) revealed
`that the median of median survival of patients treated on
`phase III trials and of patients recorded within the SEER
`database increased by 2 months between 1972 and 1990.4
`We therefore chose to review all the published North
`American Cooperative Groups and institutional phase III
`randomized therapeutic trials for patients with advanced-
`stage NSCl.C initiated (luring the time period of i973 to
`1994 in order to assess the impact of systemic chemo-
`therapy on survival over time. As platinum-based regi-
`mens were used throughout the period under review, we
`divided the analyzed trials for comparison purposes
`itccortling; to two equivalent time periods: 1973 through
`1983 and 1984 through 1994. Trials assessing combined-
`modality therapy of chemotherapy plus chest irradiation
`were not included in the analysis.
`We investigated whether the number of trials initiated
`had changed, whether the number of patients enrolled on the
`trials had increased or decreased over time, and whether
`
`survival of patients treated on these trials had improved. the
`median and 5-year survival
`information on patients with
`advanced-stage NSCLC from the last 25 years is available
`on the SEER database. This database provides the data with
`which to compare the outcomes of patients with advanced-
`stage NSCLC in both cooperative groups and in a popula-
`tion database.
`
`i734
`
`Journal ol Clinical Oncology, Vol l9, No 6 (March l5), 2001: pp l734~l742
`
`t r
`Downloaded from jcoascopubsorg on October 24, 2010. For personal use only. No other uses without permission.
`Copyright © 2001 American Society of Clinical Oncology. A ights reserved.
`OSI EXHIBIT 2009
`APOTEX V. OSI
`IPR2016-01284
`
`OSI EXHIBIT 2009
`APOTEX V. OSI
`IPR2016-01284