EMCTO 2013 News: Meta-analysis slightly favours platinum-based first-line treatment in patients with advanced/metastatic NSCLC

Cisplatin associated with survival improvement in the meta-analysis of randomised clinical trials of first-line platinum- vs. non-platinum-based regimens in patients with advanced/metastatic NSCLC.

Cisplatin associated with survival improvement in the meta-analysis of randomised clinical trials of first-line platinum- vs. non-platinum-based regimens in patients with advanced/metastatic NSCLC.
Credit for image: Dr Thierry Berghmans gave permission for publishing the images in the ESMO web news and post-EMCTO Scientific report.

Several meta-analysis conducted in the past suggest that survival of patients with advanced non-small cell lung cancer (NSCLC) is improved if first-line chemotherapy includes platinum derivatives. Results from a new meta-analysis of randomised clinical trials show that platinum-based regimens improve slightly survival in comparison with non-platinum ones and this effect is restricted to cisplatin combinations. The findings were presented by Dr Thierry Berghmans of the Department of Intensive Care and Emergencies and the Clinic of Thoracic Oncology, Institute Jules Bordet in Brussels, Belgium at the European Multidisciplinary Conference in Thoracic Oncology (EMCTO), held 9-11 May, 2013 in Lugano, Switzerland.

It is well known that cisplatin-based regimens improve survival in comparison to best supportive care alone in patients with advanced NSCLC. However, cisplatin has many adverse events that impact on quality of life while other active agents with different toxicity profiles are currently available. Cisplatin adverse events affect mostly nervous and renal systems, while carboplatin shows a different toxicity profile and it is is easier to administer in everyday practice. Several meta-analyses performed in the past suggest that survival is improved in case of platinum-based combination. Since the oncologists aim to improve the treatment outcomes and other active agents are available for clinical use, a thorough evaluation of the literature to include recent large clinical trials was warranted.

The Belgian researchers evaluated all studies published in the French and English languages in the literature that compared first-line platinum to non-platinum regimens in patients with advanced/metastatic NSCLC. For each of 25 studies that were published between 2001 and 2012 and were eligible for the systematic review, the authors extracted an estimate of the hazard ratio (HR) associated with platinum or non-platinum treatment and combined the individual HRs into an aggregate HR for each treatment modality. Either a fixed or a random-effects model (if heterogeneity was statistically significant) was used for this purpose, using data from 23 trials that allowed a quantitative aggregation for meta-analysis.

The number of patients per trial ranged from 80 to 557 and totalled 6930 for all trials. Cisplatin was the comparator in 15 trials involving 4644 participants and carboplatin was compared in 8 trials comprised of 2286 patients; the HRs for these treatments were 1.099 and 1.75. Values for the heterogeneity test with cisplatin was p=0.53 and with carboplatin was p=0.001. In all 23 studies, the HR was 1.084 (p=0.02).

Only four studies demonstrated a statistically significant survival difference between treatments, with three studies favouring platinum and one in favour of non-platinum therapy. Overall, the data showed a slightly improved survival in patients who received platinum-based regimens over patients treated with non-platinum containing regimens; however this effect was seen only with cisplatin combinations.

Ongoing analyses of patient subgroups according to quality trial assessment (based on Cochrane guidelines) and to the type of non-platinum comparator are underway to better define the role of non-platinum regimens for first-line treatment of patients with advanced NSCLC.

The study discussant, Dr Elisabeth Quoix, said that this meta-analysis confirmed that platinum-based doublets remain the standard treatment. Benefit of platinum-based doublets over non-platinum-based chemotherapy is essentially due to cisplatin (only a trend was seen for carboplatin). However, in special populations (patients with performance status 2, elderly patients) carboplatin-based doublet should be considered and probably superior to single new agents. Furthermore she emphasized that the high number of meta-analyses performed in advanced NSCLC reflects probably the heterogeneity of the patients included in randomized controlled trials (regarding age, performance status, etc.) which lead to conflicting or at least unconclusive results. Thus meta-analyses are required to answer important questions, but a good question is why repeated results of repeated meta-analyses do not convince doctors to modify their clinical attitude.

EMCTO is organised in partnership between the European Society for Medical Oncology (ESMO), The European Society for Radiotherapy and Oncology (ESTRO), the European Society of Thoracic Surgeons (ESTS) and the European Respiratory Society (ERS), and the European Thoracic Oncology Platform (ETOP). The five partners have created a programme that integrated perspectives from the different disciplines and demonstrated how the multidisciplinary team can combine knowledge for personalised treatment of the whole range of thoracic oncology tumours.

All authors have declared no conflicts of interest.