The Role of Neoadjuvant Chemotherapy in Patients With Resectable Malignant Pleural Mesothelioma—An Institutional and National Analysis

Abstract

Background There is no standard of care with respect to the use of neoadjuvant chemotherapy (NAC) in resectable malignant pleural mesothelioma (MPM). We performed an intention-to-treat analysis with data from a single institution and the National Cancer Database (NCDB) to identify whether the use of NAC impacts survival in resectable MPM. Methods Patients with MPM who had surgery with curative intent at Duke University from 1995 to 2017 were selected, and the 2004–2015 NCDB was used to identify MPM patients with clinical stage I–IIIB who underwent definitive surgery. For both cohorts, patients were stratified by receipt of NAC. Primary outcomes were overall survival and postresection survival (RS), which were estimated using Kaplan-Meier and multivariable Cox proportional hazards models. Results A total of 257 patients met inclusion criteria in the Duke cohort. Compared with immediate resection (IR), NAC was associated with similar overall survival but an increased risk for postresection mortality in both unmatched (adjusted hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.21 to 2.83) and propensity-matched (HR = 1.62, 95% CI = 1.03 to 2.55) cohorts. A total of 1949 NCDB patients were included: 1597 (81.9%) IR and 352 (18.1%) NAC. RS was worse for patients undergoing NAC in both unmatched (HR = 1.85, 95% CI = 1.21 to 2.83) and propensity-matched (HR = 1.29, 95% CI = 1.06 to 1.57) analyses compared with patients receiving IR. Conclusions In this intention-to-treat study, NAC was associated with worse RS compared with IR in patients with MPM. The risks and benefits of induction therapy should be weighed before offering it to patients with resectable MPM.

The Impact on Outcome by Adding Bevacizumab to Standard Induction Chemotherapy Prior to Mesothelioma Surgery: A Retrospective Single Center Analysis

“…In this propensity score matched retrospective analysis, 22 patients with malignant pleural mesothelioma were treated with induction chemotherapy consisting of platinum-based/ pem with bevacizumab prior to surgery compared to 66 patients receiving standard induction chemotherapy with platinum-based/pemetrexed alone. Whereas the concept of a multimodality treatment is widely accepted and recommended for this disease, the timing of chemotherapy before or after surgery is discussed controversially (1,10,11) and currently investigated in a multicenter randomized phase II trial by the In the present analysis, adding bevacizumab to standard induction chemotherapy did not significantly increase perioperative, in particular not bleeding, complications, although the proportional number of postoperative blood products and PE were higher compared to the control group. The small sample size and the lack of randomization do not allow to draw any conclusion to fully answer this question as well as the fact that PE is in general a known side effect of also the other chemotherapeutic agents.…”

“…In this propensity score matched retrospective analysis, 22 patients with malignant pleural mesothelioma were treated with induction chemotherapy consisting of platinum-based/pem with bevacizumab prior to surgery compared to 66 patients receiving standard induction chemotherapy with platinum-based/pemetrexed alone. Whereas the concept of a multimodality treatment is widely accepted and recommended for this disease, the timing of chemotherapy before or after surgery is discussed controversially ( 1 , 10 , 11 ) and currently investigated in a multicenter randomized phase II trial by the EORTC [The European Organization for Research and Treatment of Cancer (NCT 02436733)].…”

Role of induction and adjuvant systemic treatment in mesothelioma: narrative review

“…Therefore, at this time, post-operative radiotherapy is usually neither feasible nor effective in the post-operative setting. An analysis of the National Cancer Data Base (n=1,949) as well as the Duke University database (n=257) in 2020 failed to demonstrate any benefit from induction therapy (20). In fact, it reached the opposite conclusion, demonstrating that induction therapy actually increased post-resection mortality (HR =1.29 for the NCDB data, HR =1.62, for propensity matched data).…”

A Glimpse in the Future of Malignant Mesothelioma Treatment

“…Neoadjuvant treatments have been the object of active investigation, yielding mixed results. As a whole, neoadjuvant chemotherapy granted no survival advantage ( Voigt et al, 2020 ). Neoadjuvant radiotherapy was recently evaluated in a phase II trial (SMART), that showed only the feasibility of this technique ( Cho et al, 2021 ).…”