Review
Maintenance therapy in non-small cell lung cancer Expert Review of Anticancer Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 06/05/15 For personal use only.
Expert Rev. Anticancer Ther. Early online, 1–8 (2015)
Giovenzio Genestreti*, Monica Di Battista, Giovanna Cavallo, Marco Bartolotti and Alba A Brandes Department of Medical Oncology, Azienda USL, Bellaria Hospital – IRCCS Institute of Neurological Sciences, Bologna, Italy *Author for correspondence: Tel.: +39 051 6225102 [email protected]
Several randomized trials have investigated the role of maintenance treatment for patients with advanced non-small cell lung cancer (NSCLC) not progressed after completion of first-line chemotherapy, with good performance score (PS) and no persistent chemotherapy-induced toxicity. Two separate strategies have been developed: the immediate use of non-cross-resistant drug (switch maintenance or early second-line therapy) or the continuation of platinum partner alone (continuation maintenance) or in combination with other drug (combination maintenance). Here we discuss how the benefits demonstrated in these studies may change clinical practice (in terms of potential toxicity and costs) and reflect on factors that may identify subgroups of patients who might benefit from maintenance therapy in general, and which maintenance therapy specifically. KEYWORDS: advanced non-small cell lung cancer . lung cancer . maintenance therapy . Phase III randomized trial .
review
Platinum-containing (carboplatin or cisplatin) doublet chemotherapy represents the gold standard in the treatment of advanced nonsmall cell lung cancer (NSCLC) [1–4] but, unfortunately, outcome results are disappointing, with only 5% of patients alive at 5 years. (National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer, Version 3, 2012. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.) Recently, tyrosine kinase inhibitors (TKIs), such as afatinib erlotinib or gefitinib, improved survival in patients with activating mutation of epidermal growth factor receptor (EGFR). In the absence of this gene signature, an attempt to improve survival is done through the prolongation of first-line chemotherapy. Five prospective randomized trials [5–9], enrolling >1300 patients, addressed the issue of the optimal duration of platinumbased first-line chemotherapy. All these studies showed that prolongation of platinum containing chemotherapy yielded no survival benefit and exposed patients to a higher risk of severe side effects. Moreover, Rossi et al. [10] in a meta-analysis confirmed that four courses of platinum-based treatment are the optimal duration of first-line chemotherapy. A compromise between compliance and prolongation of first-line chemotherapy may be
informahealthcare.com
10.1586/14737140.2015.1052410
achieved by using non-platinum agents, both chemotherapeutic and biological. This strategy, termed ‘maintenance therapy’, can be divided into two modalities: continuation and switch maintenance. Continuation maintenance is the prosecution of one or more drugs (combination maintenance) used in firstline regimen; switch maintenance or early second line, introduces an additional agent immediately after completion of platinum doublet chemotherapy. This review discusses the recent results from trials investigating these strategies and the relevance of this evidence for the management of patients with advanced NSCLC. Methods
Data were gathered from clinical trials available in the literature on maintenance therapy in advanced NSCLC. In order to retrieve information on clinical trial in this setting, data were obtained from PubMed, Cochrane Library, American Society Clinical Oncology (ASCO) meeting published abstract, European Society of Medical Oncology (ESMO) meeting published abstract and International Association Study Lung Cancer (IASLC) meeting published abstracts, using the key words ‘maintenance therapy’, ‘Phase III randomized trial’, ‘advanced Non-Small Cell Lung Cancer’.
2015 Informa UK Ltd
ISSN 1473-7140
1
Review
Genestreti, Di Battista, Cavallo, Bartolotti, Brandes
Expert Review of Anticancer Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 06/05/15 For personal use only.
Table 1. Continuation maintenance trials. Author (year)
Pts
First-line therapy
Study arms
PFS (month)
HR
p-value
OS (month)
HR
p-value
Ref.
Belani et al. (2003)
130
Carboplatin and paclitaxel
Paclitaxel versus observation
7.3 9.5
NR
NR
18.8 15
NR
NR
[11]
Brodowicz et al. (2006)
352
Cisplatin and gemcitabine
Gemcitabine versus BSC
3.6 2.0
NR
Maintenance therapy in non-small cell lung cancer Expert Review of Anticancer Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 06/05/15 For personal use only.
Expert Rev. Anticancer Ther. Early online, 1–8 (2015)
Giovenzio Genestreti*, Monica Di Battista, Giovanna Cavallo, Marco Bartolotti and Alba A Brandes Department of Medical Oncology, Azienda USL, Bellaria Hospital – IRCCS Institute of Neurological Sciences, Bologna, Italy *Author for correspondence: Tel.: +39 051 6225102 [email protected]
Several randomized trials have investigated the role of maintenance treatment for patients with advanced non-small cell lung cancer (NSCLC) not progressed after completion of first-line chemotherapy, with good performance score (PS) and no persistent chemotherapy-induced toxicity. Two separate strategies have been developed: the immediate use of non-cross-resistant drug (switch maintenance or early second-line therapy) or the continuation of platinum partner alone (continuation maintenance) or in combination with other drug (combination maintenance). Here we discuss how the benefits demonstrated in these studies may change clinical practice (in terms of potential toxicity and costs) and reflect on factors that may identify subgroups of patients who might benefit from maintenance therapy in general, and which maintenance therapy specifically. KEYWORDS: advanced non-small cell lung cancer . lung cancer . maintenance therapy . Phase III randomized trial .
review
Platinum-containing (carboplatin or cisplatin) doublet chemotherapy represents the gold standard in the treatment of advanced nonsmall cell lung cancer (NSCLC) [1–4] but, unfortunately, outcome results are disappointing, with only 5% of patients alive at 5 years. (National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer, Version 3, 2012. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.) Recently, tyrosine kinase inhibitors (TKIs), such as afatinib erlotinib or gefitinib, improved survival in patients with activating mutation of epidermal growth factor receptor (EGFR). In the absence of this gene signature, an attempt to improve survival is done through the prolongation of first-line chemotherapy. Five prospective randomized trials [5–9], enrolling >1300 patients, addressed the issue of the optimal duration of platinumbased first-line chemotherapy. All these studies showed that prolongation of platinum containing chemotherapy yielded no survival benefit and exposed patients to a higher risk of severe side effects. Moreover, Rossi et al. [10] in a meta-analysis confirmed that four courses of platinum-based treatment are the optimal duration of first-line chemotherapy. A compromise between compliance and prolongation of first-line chemotherapy may be
informahealthcare.com
10.1586/14737140.2015.1052410
achieved by using non-platinum agents, both chemotherapeutic and biological. This strategy, termed ‘maintenance therapy’, can be divided into two modalities: continuation and switch maintenance. Continuation maintenance is the prosecution of one or more drugs (combination maintenance) used in firstline regimen; switch maintenance or early second line, introduces an additional agent immediately after completion of platinum doublet chemotherapy. This review discusses the recent results from trials investigating these strategies and the relevance of this evidence for the management of patients with advanced NSCLC. Methods
Data were gathered from clinical trials available in the literature on maintenance therapy in advanced NSCLC. In order to retrieve information on clinical trial in this setting, data were obtained from PubMed, Cochrane Library, American Society Clinical Oncology (ASCO) meeting published abstract, European Society of Medical Oncology (ESMO) meeting published abstract and International Association Study Lung Cancer (IASLC) meeting published abstracts, using the key words ‘maintenance therapy’, ‘Phase III randomized trial’, ‘advanced Non-Small Cell Lung Cancer’.
2015 Informa UK Ltd
ISSN 1473-7140
1
Review
Genestreti, Di Battista, Cavallo, Bartolotti, Brandes
Expert Review of Anticancer Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 06/05/15 For personal use only.
Table 1. Continuation maintenance trials. Author (year)
Pts
First-line therapy
Study arms
PFS (month)
HR
p-value
OS (month)
HR
p-value
Ref.
Belani et al. (2003)
130
Carboplatin and paclitaxel
Paclitaxel versus observation
7.3 9.5
NR
NR
18.8 15
NR
NR
[11]
Brodowicz et al. (2006)
352
Cisplatin and gemcitabine
Gemcitabine versus BSC
3.6 2.0
NR
