BAP1-Altered Malignant Pleural Mesothelioma: Outcomes With Chemotherapy, Immune Check-Point Inhibitors and Poly(ADP-Ribose) Polymerase Inhibitors

Our plain-English summary of BAP1-Altered Malignant Pleural Mesothelioma: Outcomes With Chemotherapy, Immune Check-Point Inhibitors and Poly(ADP-Ribose) Polymerase Inhibitors, by E. Dudnik, J. Bar, A. Moore, et al (Frontiers in Oncology, 2021).

The study

• Authors: E. Dudnik, J. Bar, A. Moore, T. Gottfried, M. Moskovitz, J. Dudnik, T. Shochat, A.M. Allen, A. Zer, O. Rotem, N. Peled, D. Urban
• Journal: Frontiers in Oncology
• Published: 2021;11:603223
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Little is known regarding the outcomes of systemic treatments in BAP1-altered malignant pleural mesothelioma (MPM).

Materials And Methods: Forty five patients with MPM [group A: eight MPM patients with BAP1 inactivating mutation/copy number loss (FoundationOne® CDx/TEMPUSxT), selected from the electronic databases of four Israeli cancer centers (ICC); group B: 37 consecutive (years 2016-2018) MPM patients selected from the electronic databases of two ICC-of those six patients without a BAP1 alteration (group B1) and 31 patients not tested for BAP1 (group B2)] were analyzed for ORR, PFS (mRECIST), and OS with 1st-line platinum/pemetrexed+/-antiangiogenic drug (CT, n-28), immune check-point inhibitors (ICPi, n-16) and poly (ADP-ribose) polymerase inhibitors (PARPi, n-4). OS since diagnosis (OSDx) was assessed.

Results: There were no differences in ORR or mPFS with CT between the groups: ORR-50% vs. 47% vs. 50% vs. 47% (p>0.9), mPFS-9.1mo (95% CI, 1.2-16.1) vs. 9.2mo (95% CI, 2.9-13.3) vs. 7.2mo (95% CI, 2.3-NR) vs. 10.9mo (95% CI, 2.9-20.3) (p>0.8) in groups A, B, B1, and B2, respectively. There were no differences in ORR or mPFS with ICPi between the groups: ORR-0% vs. 27% vs. 33% vs. 25% (p>0.2), mPFS-2.5mo (95% CI, 1.4-3.7) vs. 3.0mo (95% CI, 1.3-10.5) vs. 2.0mo (95% CI, 1.9-NR) vs. 4.5mo (95% CI, 0.3-10.5) (p>0.3) in groups A, B, B1, and B2, respectively. In group A, no responses were seen with PARPi; mPFS with PARPi was 1.8mo (95% CI, 1.8-NR). OSDx was 98.3mo (95% CI, 9.7-98.3) vs. 19.4mo (95% CI, 9.7-47.3) vs. 18.8mo (95% CI, 8.5-NR) vs. 19.5mo (95% CI, 8.3-82.2) in groups A, B, B1, and B2, respectively (p>0.3).

Conclusions: BAP1-altered MPM, as compared to non-selected MPM, is characterized by similar efficacy of CT and ICPi. Numerically longer OS in BAP1-altered MPM may reflect favorable tumor biology. No responses were observed with PARPi.

Copyright © 2021 Dudnik, Bar, Moore, Gottfried, Moskovitz, Dudnik, Shochat, Allen, Zer, Rotem, Peled and Urban.

In plain English

This retrospective study reviewed 45 malignant pleural mesothelioma patients in Israel. Eight had BAP1-altered tumors (group A); 37 patients diagnosed 2016 to 2018 had no alteration (6) or were untested (31) (group B). Asbestos exposure was recorded in 2 of 8 and 15 of 37. With first-line platinum/pemetrexed chemotherapy, with or without antiangiogenic drugs (bevacizumab: 5 of 8 versus 4 of 20), 4 of 8 group A and 9 of 19 assessable group B patients responded (50% vs 47%). Median progression-free survival (until worsening or death) was 9.1 versus 9.2 months (95% CIs 1.2 to 16.1 and 2.9 to 13.3). With immune check-point inhibitors, 0 of 2 assessable group A and 3 of 11 group B patients (27%) responded. None differed significantly. Of four group A patients given PARP inhibitors, none responded. Median survival from diagnosis was 98.3 versus 19.4 months (95% CIs 9.7 to 98.3 and 9.7 to 47.3), not significant. The authors concluded BAP1 alterations did not seem to change these responses. They noted the small retrospective design and likely untested BAP1-altered tumors in group B.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis comparing treatment outcomes in patients with and without BAP1-altered tumors
• Who was studied: 45 patients with malignant pleural mesothelioma at Israeli cancer centers. Group A: 8 patients with BAP1 inactivating mutation or copy number loss (6 from two centers plus 2 found through the Israel Lung Cancer Group). Group B: 37 consecutive patients diagnosed January 2016 to December 2018, of whom 6 had no BAP1 alteration (group B1) and 31 were not tested (group B2).
• Exposure: The study examined systemic cancer treatments, not asbestos: first-line platinum/pemetrexed with or without an antiangiogenic drug (28 patients), immune check-point inhibitors (16), and PARP inhibitors (4, group A only). Asbestos exposure was recorded as a baseline characteristic: yes in 2 of 8 (25%) in group A and 15 of 37 (41%) in group B (Table 1). The difference was not statistically significant. Fiber types were not reported.
• Main results:
  • First-line platinum/pemetrexed chemotherapy was given to all 8 group A patients and 20 of 37 group B patients.
  • Among chemotherapy-treated patients, bevacizumab was added in 5 of 8 in group A (62%) and 4 of 20 in group B (20%). Two further group B patients received platinum/pemetrexed with or without nintedanib within the LUME-Meso clinical trial.
  • Objective response rate with first-line chemotherapy, with or without antiangiogenic agents, was 50% in group A (4 partial responses among 8 treated) and 47% in group B (1 complete and 8 partial responses among 19 assessable of 20 treated) (p = 0.97).
  • Median progression-free survival (from treatment start until disease progression or death) with first-line chemotherapy was 9.1 months (95% CI 1.2 to 16.1) in group A and 9.2 months (95% CI 2.9 to 13.3) in group B (p = 0.96).
  • Immune check-point inhibitors were given to 3 group A and 13 group B patients. Objective response rate was 0% in group A (0 of 2 assessable) and 27% in group B (3 partial responses among 11 assessable) (p = 0.28).
  • Median progression-free survival with immune check-point inhibitors was 2.5 months (95% CI 1.4 to 3.7) in group A and 3.0 months (95% CI 1.3 to 10.5) in group B (p = 0.39).
  • Among 4 group A patients given PARP inhibitors (veliparib or olaparib), none had an objective response. Three had progressive disease and one had stable disease. Median progression-free survival was 1.8 months.
  • Median overall survival since diagnosis was 98.3 months (95% CI 9.7 to 98.3) in group A and 19.4 months (95% CI 9.7 to 47.3) in group B (p = 0.31).
  • In univariate analysis, BAP1 alteration status was not significantly correlated with survival since diagnosis.
• The authors' conclusion: The authors concluded that BAP1 genomic aberration in malignant pleural mesothelioma does not seem to modulate responses to platinum/pemetrexed or immune check-point inhibitors. In their view, the numerically longer survival since diagnosis in BAP1-altered cases probably reflects a favorable natural history. No responses were seen in the four patients treated with PARP inhibitors.
• Limitations the authors state:
  • Retrospective design, small sample size, and no central radiological assessment.
  • Not all patients were tested for BAP1, so the comparison group B probably included BAP1-altered tumors, estimated at around 20 to 25%.
  • The authors could not tell whether the BAP1 alterations were inherited (germline) or acquired in the tumor (somatic).
  • Patients were mainly good-prognosis cases typical of tertiary cancer centers, which raises uncertainty about how representative the cohort is.
  • Centralized pathological testing of BAP1 staining was not feasible.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Pleural Mesothelioma, Chemotherapy, Pemetrexed (Alimta).

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