Before ICAP initiation, patients received gefitinib predominantly as monotherapy (84%). However, this seems unlikely because there were no obvious differences in well-established prognostic factors among the two arms despite the early termination of the study before the desired accrual was achieved. No patient‐identification information was collected. JCO Global Oncology J Clin Oncol 26:: Thatcher N, Chang A, Parikh P, et al: Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: Results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). ISEL (Iressa Survival Evaluation in Lung Cancer) was a double-blind, placebo-controlled, parallel-group, multicenter, randomized, Phase III study to assess the survival advantage of gefitinib (250 mg/day) as second- or third-line treatment for patients with locally advanced or metastatic NSCLC . In addition, there is a suggestion that NSCLCs with K-ras mutations do worse when treated with the EGFR-TKI erlotinib.25 This again raises the question of the K-ras gene status of the tumors in the SWOG study. Ando M, Okamoto I, Yamamoto N, Takeda K, Tamura K, Seto T, et al. To qualify for enrollment, patients had to have been benefiting from gefitinib for at least 3 years, because the timing of ICAP started 3 years after gefitinib was made unavailable for new prescription starts in the United States. Lancet 366:: Hirsch FR, Varella-Garcia M, Cappuzzo F, et al: Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. Unfortunately, early randomized trials of gefitinib were designed before the discovery of EGFR mutations and their significance in NSCLC. Kelly K, Chansky K, Gaspar LE, et al: Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non–small-cell lung cancer: SWOG S0023. Lynch et al. Gefitinib was the first EGFR-TKI evaluated in a phase III trial. As is well known, both radiotherapy and docetaxel can cause pulmonary fibrosis,9,10 and interstitial lung disease has been observed after gefitinib therapy.11 In addition, interstitial lung disease seems to be even more problematic after gefitinib therapy in individuals with pre-existing pulmonary fibrosis.11 Thus, one might suppose that the combination of these therapies would be a near perfect situation for causing significant pulmonary toxicity. DOI: 10.1200/JCO.2008.16.0374 Journal of Clinical Oncology
There were 23 deaths, of which none were related to gefitinib‐related SAEs; 9 were from lung cancer, 5 were from other nongefitinib‐related causes, 5 were from SAEs not related to gefitinib, and 4 were from unknown causes. Subscribers The intent was to include as many patients enrolled into the ICAP as feasibly possible (of 191 patients from 137 sites), and enrollment was contingent on investigator interest in chart review participation. Dara Stein: Study conception and design, patient recruitment, data collection, data analysis and interpretation, statistical analysis, writing–initial draft, and writing–review and editing. Contact Us Elisabeth F. Croft is an employee of Incyte Corporation and was an employee of AstraZeneca at the time of the study. Accordingly, excess toxicity caused by an adverse interaction between EGFR blockade and irradiation does not seem to be the explanation for the S0023 results. The clinical courses and survival of patients with lung cancer, who have EGFR mutations as deletions in exon 19 or L858R, can be changed with gefitinib treatment. Learn more about types of lung cancer, survival rates, and other statistics. Frontline treatment with apatinib in combination with gefitinib (Iressa) demonstrated superior progression-free survival (PFS) in patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC), according to results from the phase 3 ACTIVE trial (NCT02824458).1. Med Oncol 23:: Bonner JA, Harari PM, Giralt J, et al: Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck.
Additional supporting information may be found in the online version of this article. How then do we explain these rather surprising and disappointing results? Lynch TJ, Bell DW, Sordella R, et al. Gefitinib (Iressa, AstraZeneca) can prolong survival with less toxicity compared with chemotherapy. JCO Oncology Practice The study involved no intervention and thus did not affect patient treatment. The 1-year survival was 59% for the no prior chemotherapy patients and 39% for the previously treated cohort (Figure 3).
Nat Biotechnol 23:: 2318 Mill Road, Suite 800, Alexandria, VA 22314, © 2020 American Society of Clinical Oncology. Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. This study was funded by AstraZeneca (Wilmington, DE). George Simon reports grants from Boehringer Ingelheim and Merck outside the submitted work and personal fees from Celgene, Genentech, Lilly, Ariad, Genprex Inc, and RefleXion Medical. An overview of the study cohort enrollment is presented in Supporting Figure 1. The third patient remained on gefitinib after the onset of the SAEs (lung infection and chronic obstructive pulmonary disease exacerbations) and died of exacerbation of chronic obstructive pulmonary disease 11 weeks later.
It is now standard of care across the country — and probably the world — to screen … In ancient Greek, khaos or chaos means “gaping void.” The results of S0023 illustrate the ongoing gaping void in our understanding of lung cancer biology and the importance of continued bench to bedside to bench investigations. Improvements in survival are being seen across the spectrum of EGFR -mutant non–small cell lung cancer (NSCLC) in patients with resectable, oligometastatic, and metastatic disease with … Use the link below to share a full-text version of this article with your friends and colleagues. Lung Cancer … In all firstline RCTs comparing EGFR-TKI against chemotherapy in patie… In addition to the SAEs reported for all patients in the overall ICAP populations, other safety information and adverse events (AEs) were extracted during ICAP. Published online
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