Lung Cancer
Maintenance Chemotherapy for Advanced Non-small-cell Lung Cancer
Shirish M Gadgeel
Associate Professor, Division of Hematology/Oncology, Department of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University
Abstract
Platinum-based combination chemotherapy, the current standard of care, enables modest improvements in survival and quality of life in patients with advanced non-small-cell lung cancer (NSCLC). In recent years, maintenance therapy in the form of either extended therapy or therapy with a different drug in patients deriving clinical benefit from initial treatment has been investigated. Extension of initial chemotherapy has shown improvements in time to tumour progression, but has not led to improved survival. Extension of chemotherapy is also associated with cumulative toxicities. Targeted agents such as bevacizumab and cetuximab can be extended until progression. However, the clinical benefits of continuing these agents until progression are unclear. Recently, a strategy of initiating treatment with a different drug following initial therapy has shown significant improvements in both progression-free survival and overall survival. Even though the applicability of this maintenance strategy may be limited to select patients, these data have established maintenance chemotherapy as a therapeutic option for advanced NSCLC patients.
Keywords
Maintenance therapy, non-small-cell lung cancer (NSCLC), pemetrexed, erlotinib, docetaxel
Disclosure: Shirish M Gadgeel has received research support from Eli Lilly, AstraZeneca and Genentech, sits on the advisory boards of Eli Lilly, Genentech and AstraZeneca and is on the speaker’s bureau of Eli Lilly and Genentech. Received: 21 September 2009 Accepted: 19 October 2009 Citation: European Oncology, 2010;6(1):47–50 Correspondence: Shirish M Gadgeel, Associate Professor, Division of Hematology/Oncology, Department of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, 4100 John R, 4HWCRC, Detroit, MI 48201, US. E:
gadgeels@karmanos.org
Advanced stage of non-small-cell lung cancer (NSCLC) at presentation among many patients is the main reason for the poor survival observed in this disease. Systemic chemotherapy with platinum- based regimens is the current standard of therapy for patients with advanced NSCLC. However, such therapy provides only modest improvements in survival and quality of life. The median progression- free survival (PFS) with platinum-based chemotherapy is about five months and the overall survival (OS) is approximately 10 months. Various strategies including three-drug combinations did not result in a significantly superior outcome compared with two-drug platinum- based combinations. This led to the wide acceptance of the concept that we had reached a ‘chemotherapy plateau’ in advanced NSCLC. A strategy to improve outcomes has been to extend therapy or introduce a different drug in patients deriving clinical benefit from initial treatment. Recent clinical trial data have suggested that such a strategy can provide benefit for NSCLC patients. This article will consider the data and provide a perspective on the applicability of this strategy, termed maintenance therapy, in the management of advanced NSCLC patients.
Extended Chemotherapy
The guidelines published by the American Society of Clinical Oncology (ASCO) in 2004 state that first-line chemotherapy treatment should be limited to four cycles in non-responsive patients and six cycles in responsive patients (see Table 1).1
One strategy to improve outcomes of patients with advanced NSCLC has been to continue treatment
© TOUCH BRIEFINGS 2010
with the same chemotherapy. Trials evaluating this strategy either assessed higher number of cycles or continued therapy until progression. Earlier trials using older regimens to evaluate this strategy failed to show any improvement in time to tumour progression (TTP) or OS.2–4
The data with current therapeutic regimens suggest that prolonging systemic therapy may increase TTP, but does not increase OS. Socinski et al. compared four cycles of carboplatin and paclitaxel with therapy until disease progression.5
The primary end-point of this
study was one-year survival. The median survival and one-year survival with a defined number of cycles were 6.6 months and 28% versus 8.5 months and 34% in patients who received therapy until progression (p=0.63). von Plessen et al. assessed three versus six cycles of carboplatin and vinorelbine.6
The primary end-point of this
study was quality of life and survival. The study found no difference in any of the end-points between the two arms. Park et al. assessed four versus six cycles of chemotherapy in patients who had responding or stable disease after two cycles.7
The primary end-point of this study
was OS. This study demonstrated similar survival between patients who received four or six cycles. However, the study did observe a significant difference in TTP with six cycles of therapy: 6.2 versus 4.6 months (p=0.001). In a similar study, Barata et al. assessed four versus six cycles of therapy with carboplatin and gemcitabine and found improved survival in patients who received six cycles of therapy, although TTP was similar in the two arms.8
The median
47
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100