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ES19 - Recently Diagnosed Malignant Pleural Effusion (ID 22)
- Event: WCLC 2019
- Type: Educational Session
- Track: Interventional Diagnostics/Pulmonology
- Presentations: 1
- Now Available
- Moderators:Juan Carlos Trujillo-Reyes, Julius Janssen
- Coordinates: 9/09/2019, 14:00 - 15:30, Tokyo (1982)
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ES19.04 - How to Deal with a Trapped Lung (Now Available) (ID 3259)
14:00 - 15:30 | Presenting Author(s): Y C Gary Lee
- Abstract
- Presentation
Abstract
TRAPPED LUNG AND MALIGNANT PLEURAL EFFUSIONS
Y C Gary Lee MBChB PhD FRACP FRCP FCCP
Professor of Respiratory Medicine, University of Western Australia
Trapped lung, now also called nonexpandable lung, refers to the observation when an underlying lung fails to fully expand upon removal of pleural fluid or air [1]. It occurs in ~30% of patients with malignant pleural effusions (MPEs) and may arise from thickened visceral pleura (inhibiting lung expansion) or from endobronchial tumor obstruction. The pleural space in patients with nonexpandable lung is usually under high negative pressure. This can lead to transudative fluid accumulation by Starling’s equation, in addition to the underlying MPE formation. This condition is often difficult to manage as fluid often keep recurring to fill up the trapped lung space.
Patients with MPE and trapped lung often present with breathlessness. It is important to recognize that removal of the fluid can still provide symptom relief despite the nonexpendable underlying lung [2]. A trial of fluid drainage to determine if the patient has symptoms benefits is worthwhile. The current belief is that breathlessness from MPE is a result of altered respiratory mechanics when the hemithorax expands to accommodate the volume of the effusion (see our review [2] for details).
Patients with nonexpandable lungs usually do not benefit from pleurodesis due to the lack of apposition of the visceral and parietal pleura. Indwelling pleural catheter (IPC) is now a recognized first choice management of MPE in patients with a nonexpendable lung, as recommended in the latest American thoracic Society MPE guidelines (2018) [3]. Several large randomized studies in recent years have testified to the benefits of IPC management of MPEs. The TIME-2 study [4] showed that IPC offered benefits to breathlessness and chest pain similar to conventional talc slurry pleurodesis. The AMPLE trial [5] showed that patients with MPE managed with IPC spent fewer days in hospital and required fewer pleural invasive procedures in their remaining life while enjoying the same level of symptom and quality-of-life improvements as those patients treated with talc pleurodesis. The recently published AMPLE-2 study [6] compared daily catheter drainage vs symptom-guided drainage in patients with MPEs and an IPC. Interestingly 50% of those with initial trapped lung who underwent daily drainage eventually developed spontaneous pleurodesis that allow removal of the catheter. The numbers however were small and the results require verification.
Conventionally it is believed that surgical decortication of the lung in MPE patients with visceral pleural thickening may allow the lung to re-expand and thus permit successful pleurodesis. Limited objective data exist to support this belief (see our recent review [7]). In the VATS-Meso trial [8] and other observational series, patient who underwent VATS pleurodesis +/- pleurectomy have higher risks of complications especially prolonged post-operative air-leak and thus hospitalization. The planned AMPLE-3 randomized trial will compare IPC treatment with surgical pleurodesis for MPE.
Patients with MPEs and underlying nonexpandable lung are often excluded in clinical trials and thus their optimal management remains unclear. They represent a sizeable subset of MPE patients and deserve specific attention in future research.
REFERENCES
1. Light RW, Lee YCG. Textbook of Pleural Dieaseas. 3rd ed. USA: Taylor & Francis; 2016.
2. Thomas R, Jenkins S, Eastwood PR, et al. Physiology of breathlessness associated with pleural effusions. Curr Opin Pulm Med. 2015;21(4):338-45.
3. Feller-Kopman DJ, Reddy CB, DeCamp MM, et al. Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(7):839-49.
4. Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-9.
5. Thomas R, Fysh ETH, Smith NA, et al. Effect of an Indwelling Pleural Catheter vs Talc Pleurodesis on Hospitalization Days in Patients With Malignant Pleural Effusion: The AMPLE Randomized Clinical Trial. JAMA. 2017;318(19):1903-12.
6. Muruganandan S, Azzopardi M, Fitzgerald DB, et al. Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial. Lancet Respir Med. 2018;6(9):671-80.
7. Fitzgerald DB, Koegelenberg CFN, Yasufuku K, et al. Surgical and non-surgical management of malignant pleural effusions. Expert Rev Respir Med. 2018;12(1):15-26.
8. Rintoul RC, Ritchie AJ, Edwards JG, et al. Efficacy and cost of video-assisted thoracoscopic partial pleurectomy versus talc pleurodesis in patients with malignant pleural mesothelioma (MesoVATS): an open-label, randomised, controlled trial. Lancet. 2014;384(9948):1118-27.
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MA23 - Preclinical Models and Genetics of Malignant Pleural Mesothelioma (ID 353)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Mesothelioma
- Presentations: 1
- Now Available
- Moderators:Ramon Palmero Sánchez, Raphael Bueno
- Coordinates: 9/10/2019, 14:30 - 16:00, Copenhagen (1980)
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MA23.01 - Phase II Trial of an Oral FGFR Inhibitor AZD4547 as Second or Third Line Therapy in Malignant Pleural Mesothelioma: Final Results of FRAME Study (Now Available) (ID 2208)
14:30 - 16:00 | Author(s): Y C Gary Lee
- Abstract
- Presentation
Background
Treatment options are limited after first line platinum-based therapy for malignant pleural mesothelioma (MPM). FGFR-9 is a mitogenic ligand that activates the FGF-receptor (FGFR) family and is overexpressed in pleural fluid and tumour samples from mesothelioma patients. In mesothelioma mouse models, FGF-receptor inhibitors reduce tumour burden. Hence, we examined the efficacy of the FGFR tyrosine kinase inhibitor, AZD4547 as second/third line therapy in MPM.
Method
From April 2016 to January 2019, we conducted a single-site, single arm, open-label study of AZD4547 in patients with MPM. Eligible patients had histologically or cytologically confirmed mesothelioma, measurable disease and had progressed after first or second line therapy. Patients received oral 80mg twice-daily AZD4547 with protocol dose reductions as required. The primary end point was 6-month progression free survival (PFS6); key secondary endpoints included PFS, response rate, overall survival, and safety and tolerability. Using a Simons' two-stage design, 26 patients would be recruited to the first stage and the study would be declared negative if fewer than 7 (27%) of 26 patients achieved PFS6.
Result
24 patients (21 (87%) male), median age 69.5 (range 53-84) were recruited. Histological subtype was epithelioid (83.3%), biphasic (8.3%), sarcomatoid (8.3%). Most patients had one prior regimen (14; 58%). Common toxicities included grade 1 and 2 hyperphosphataemia, nail changes, stomatitis, and ophthalmological changes, consistent with reported toxicities of this drug class. No adverse events required hospitalisation. There were two partial responses (8%); 17 patients (70%) had stable disease (SD) for at least 6 weeks, and 5 patients (21%) had progressive disease as their best response. Three of 24 patients (12%) were progression free at 6 months. Hence, the study fulfilled stopping criteria regardless of further recruitment and was discontinued once the criteria for progressing to stage 2 could not be met. Progression free survival was 3.9 months and overall survival was 9.3 months. One patient remained on study with SD for 16 months, experiencing ongoing grade 2 hyperphosphatemia, alopecia of body and facial hair and grade 2 onycholysis.
Conclusion
The FGFR inhibitor AZD4547 was ineffective for patients with MPM who had progressed on first or second line therapy. Continuous grade 2 cutaneous and ocular toxicities were observed with prolonged therapy
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