Retrospective Evaluation of the Use of Pembrolizumab in Malignant Mesothelioma in a Real-World Australian Population

Malignant pleural mesothelioma (MPM) is an extremely aggressive plural malignancy mainly caused by asbestos exposure. Basic research about the immune suppressive tumor microenvironment in MPM has suggested that MPM might be a good candidate for immune therapy. Immunocheckpoint inhibitors have shown some promising results. A phase Ib trial with pembrolizumab, an antibody specific for the programmed cell death 1 protein (anti-PD-1), showed efficacy in patients with programmed death-ligand 1 (PD-L1)-positive MPM. Among 25 patients tested, 5 patients (20%) achieved a partial response. A Japanese group evaluated the efficacy and safety of nivolumab, an anti-PD-L1 antibody, for patients with advanced MPM in a phase II study. Ten (29%) patients showed an objective response. Based on those results, nivolumab was approved in Japan for unresectable recurrent MPM. A phase III randomized study was conducted to compare nivolumab plus ipilimumab to platinum doublet chemotherapy as a first-line therapy in unresectable MPM. The primary endpoint, overall survival (OS), was significantly improved in the nivolumab plus ipilimumab group. Cellular therapies and cancer vaccines are limited by many challenges; therefore, improvements to overcome these difficulties are urgently warranted. Further research is needed, including large-scale clinical trials, to clarify the utility and safety of immunotherapy in MPM.

show abstract

“…They found an ORR of 18%, and a disease control rate of 56%. The median PFS was 4.8 months, and the median OS was 9.5 months [22].…”

Section: Pembrolizumabmentioning

confidence: 98%

Immunotherapy in Malignant Pleural Mesothelioma

Matsuda¹,

Fujimoto²

2021

Advances in Precision Medicine Oncology

View full text Add to dashboard Cite

show abstract

“…In combination with ipilimumab (anti‐CTLA‐4), response rates were even higher and more durable. Still, the majority of patients failed to respond which could be due to lack of T‐cell infiltration before treatment 2,6 …”

Section: Introductionmentioning

confidence: 99%

“…Still, the majority of patients failed to respond which could be due to lack of T-cell infiltration before treatment. 2,6 Dendritic cell (DC) therapy has been shown to be safe, feasible and able to induce radiological responses in MPM coinciding with enhanced intratumoral T-cell infiltration. [7][8][9] As DC therapy-induced infiltrating T cells may in turn become exhausted through PD-1/PD-L1 signaling, we investigated the efficacy of adjuvant anti-PD-1 immunotherapy in DC-treated MPM patients.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Combination of PD‐1/PD‐L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma

Gulijk

Belderbos

Dumoulin

et al. 2022

Intl Journal of Cancer

View full text Add to dashboard Cite

Immunotherapy with anti‐PD1/PD‐L1 is effective in only a subgroup of patients with malignant pleural mesothelioma (MPM). We investigated the efficacy of a combination of anti‐PD1/PD‐L1 and dendritic cell (DC) therapy to optimally induce effective anti‐tumor immunity in MPM in both humans and mice. Data of nine MPM patients treated with DC therapy and sequential anti‐PD1 treatment were collected and analyzed for progression‐free survival (PFS) and overall survival (OS). Survival and T‐cell responses were monitored in AC29 mesothelioma‐bearing mice treated concurrently with the combination therapy; additionally, the role of the tumor‐draining lymph node (TDLN) was investigated. The combination therapy resulted in a median OS and PFS of 17.7 and 8.0 months, respectively. Grade 3 to 4 treatment‐related adverse events had not been reported. Survival of the mesothelioma‐bearing mice treated with the combination therapy was longer than that of untreated mice, and coincided with improved T‐cell activation in peripheral blood and less T‐cell exhaustion in end stage tumors. Comparable results were obtained when solely the TDLN was targeted. We concluded that this combination therapy is safe and shows promising OS and PFS. The murine data support that PD‐L1 treatment may reinvigorate the T‐cell responses induced by DC therapy, which may primarily be the result of TDLN targeting.

show abstract

“…Among others, this is what is happening with mesothelioma (a pleural cancer mainly due to asbestos exposure) where after a long period of time when tremelimumab and pembrolizumab were hailed as a revolution for this tumor on the basis of earlier small studies (“ the syrup that melts tumors” ( Fondazione Buzzi Unicem, 2016 ), until the results of randomized clinical trials and real-world evidence with overall survival as end points have demonstrated their inefficacy ( Maio et al, 2017 ; Popat et al, 2020 ) and pointed out how the outcome was rather biased by performance status real-world evidence ( Ahmadzada et al, 2020 ; Lau et al, 2020 ).…”

mentioning

confidence: 99%

Is There Already a Need of Reckoning on Cancer Immunotherapy?

et al. 2021

View full text Add to dashboard Cite

The last decades of translational research on cancer immunobiology are allowing the design of profoundly innovative treatments for cancer. Nonetheless, within the scientific community, there is raising concern on the real impact of some of these new possible therapeutic opportunities and on how they are communicated to both health-carers and general public.Results from randomized clinical trials, which are the gold standard for determining the efficacy of a new treatment, are oftentimes reported as highly successful, despite some significant limitations. A recent survey analyzed over 3,000 randomized controlled trials published in the Journal of the American Medical Association, the Lancet, and the New England Journal of Medicine, to identify low-value medical practices that increase costs without improving care. The authors showed that 396 out of all randomized trials regarding a wide range of medical specialties, including oncology, had not provided results to justify the change of clinical practice as previously supposed (Herrera-Perez et al., 2019).Also, it is increasingly recognized that some of these trial results should be significantly downsized prior to achieving more convincing validation in the real-world setting (Martini et al., 2020).Lancet Oncology (The Lancet Oncology, 2018) itself published an authoritative editorial raising a serious warning on the threat posed by the "hype" and information spread across on cancer immunotherapy, and more in general on many new cancer therapies.Other authors have addressed the risk of miscommunication when poorly reported responses of single patients end up to upstage and replace real achievements based on solid background and validated figures (Nishikawa et al., 2018). This miscommunication leads to high expectations and strong requests from patients and their families, and often clinicians are urged to treat patients with therapies that need a more solid validation.The hype on some trial results can also affect the drug regulatory practice (Martini et al., 2020); indeed, various cancer drugs have been approved without control arms only in 2019 (CG, 2020). Also concerning is the fact that some studies did not compare new treatments with the best treatment available (Zalcman et al., 2016;Hilal et al., 2019;IASLC, 2020). Other findings show that 67% of the trials which led to anticancer drug marketing authorization by the Food and Drug Administration (FDA) between 2014 and 2019 failed the criteria needed: randomized design, demonstration of survival advantage, appropriate use of crossover, and optimal control arms (Hilal et al., 2020). Similarly, an analysis of pivotal randomized controlled trials of new antitumoral agents approved by the European Medicines Agency (EMA) between 2014 and 2016 concluded that almost half showed a high risk of bias based on their design, conduct, or analysis (Naci et al., 2019).Other groups have stigmatized that general clinical trials run by not-for-profit organizations are significantly less likely to recommend a new treatment compar...

show abstract

Retrospective Evaluation of the Use of Pembrolizumab in Malignant Mesothelioma in a Real-World Australian Population

Cited by 14 publications

References 51 publications

Immunotherapy in Malignant Pleural Mesothelioma

Immunotherapy in Malignant Pleural Mesothelioma

Combination of PD‐1/PD‐L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma

Is There Already a Need of Reckoning on Cancer Immunotherapy?

Contact Info

Product

Resources

About