The results of the long-awaited AMPLE-2 study comparing the effect of daily versus as-needed drainage of malignant pleural effusions via indwelling pleural catheters (IPCs) were published in July in The Lancet Respiratory Medicine.
This study adds clarity to the management of patients with malignant pleural effusions, a topic that has interested pleural researchers for several years now. Based on the AMPLE-2 results, the authors suggest that patients for whom catheter removal is a priority should consider daily drainage, while those primarily concerned with symptom relief may benefit from draining on an as-needed basis without concerns for worse breathlessness or pain, as this may relieve some of the burden and costs (co-pays) associated with daily drainage.
Several observations should in addition be considered.
First, the only firm conclusion that can be drawn from this study is that daily drainage is not associated with improved breathlessness scores at 60 days compared to as-needed drainage. All other endpoints are secondary, thus hypothesis-generating and should form the basis for future research. Specifically, the between-group difference in the EuroQoL-5 Dimensions-5 Levels score, after adjustment for minimization variables and baseline values, is barely clinically (and statistically) significant (0.097 for a minimally clinically important difference estimated at 0.09, p=0.0408). Given similar breathlessness and pain scores, it is difficult to interpret these results.
Second, while significantly higher (37.2 vs 11.4%), the rates of spontaneous pleurodesis associated with daily drainage continue to pale in comparison with historical rates of inpatient talc pleurodesis. Breathlessness relief, and not pleurodesis, is the raison d’être of indwelling pleural catheters. Unless aggressive daily drainage via IPC in association with some type of pleurodesis is eventually demonstrated to achieve similar pleurodesis rates as those seen with conventional talc pleurodesis, it seems difficult to recommend this strategy in the majority of cases. It is also important to point out that mesothelioma, a primary pleural tumor associated with higher rates of pleurodesis, represented approximately one third of tumors in both groups, which make pleurodesis rates difficult to generalize to other populations.
Finally, cost-effectiveness studies from a patient perspective, rather than from the perspective of third-party payers, are urgently needed. In some countries, like the US, out-of-pockets costs from consumables associated with daily drainage (particularly when IPCs are bilateral) are sometimes prohibitive. Future studies comparing aggressive drainage with pleurodesis to as-needed drainage aimed at symptom relief should consider as a predefined endpoint the financial burden imposed on patients.