1615O - Pembrolizumab as second or further line treatment in relapsed malignant pleural mesothelioma; a Swiss Registry

Date 10 September 2017
Event ESMO 2017 Congress
Session Mesothelioma and SCLC
Topics Mesothelioma
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Laetitia Mauti
Citation Annals of Oncology (2017) 28 (suppl_5): v568-v572. 10.1093/annonc/mdx389
Authors L.A. Mauti1, D. Klingbiel2, S. Schmid3, H. Bouchaab4, T. Bartnick5, O. Gautschi6, S.I. Rothschild7, M. Loeffler-Baumann8, P. Froesch9, U. Petrausch10, S. Wolleb Schild11, W. Mingrone12, S. Pratsch Peter13, S. Savic Prince14, M. Pless1, R. von Moos15, Y. Metaxas15
  • 1Medizinische Onkologie, Kantonsspital Winterthur, 8401 - Winterthur/CH
  • 2Coordinating Center, SAKK, 3000 - berne/CH
  • 3Medizinische Onkologie, Kantonsspital St. Gallen, 9000 - St. Gallen/CH
  • 4Service D'oncologie Médicale, Centre Hospitalier Universitaire Vaudois - CHUV, 1011 - Lausanne/CH
  • 5Medizinische Onkologie, Kantonsspital Baden, 5404 - Baden/CH
  • 6Medizinische Onkologie, Luzerner Kantonsspital, 6004 - Luzern/CH
  • 7Medizinische Onkologie, Universitätsspital Basel, 4031 - Basel/CH
  • 8Onkologie, Kantonsspital Aarau ZOHT, 5001 - Aarau/CH
  • 9Oncologia Medica, IOSI Istituto Oncologico Svizzera Italiana, 6600 - Locarno/CH
  • 10Medizinische Onkologie, OnkoZentrum Zürich, 8038 - Zürich/CH
  • 11Medizinische Onkologie, Spital Uster, 8610 - Uster/CH
  • 12Medizinische Onkologie, Kantonsspital Olten, 4600 - Olten/CH
  • 13Medizinische Onkologie, Stadtspital Waid, 8037 - Zürich/CH
  • 14Institute Of Pathology, University Hospital Basel, 4031 - Basel/CH
  • 15Medizinische Onkologie, Kantonsspital Graubünden, 8000 - Chur/CH

Abstract

Background

Available 2nd line chemotherapies for relapsed malignant pleural mesothelioma (MPM) have limited activity. Results from early clinical trials - including the mesothelioma cohort of the KEYNOTE-028 phase I/II trial - show promising activity of various PD-(L)1 checkpoint inhibitors in MPM. Pembrolizumab has been used off-label in Switzerland as 2nd and further line treatment in patients with MPM.

Methods

Cancer centers in Switzerland entered data on patients having received pembrolizumab for MPM into this retrospective registry. Patient characteristics including age, gender, histology, stage at diagnosis and previous treatments were collected. Outcomes of pembrolizumab were assessed by the local investigators using standard RECIST v1.1 criteria. PD-L1 expression was determined centrally.

Results

We collected data on 48 patients (median age 68 years) having received pembrolizumab for relapsed MPM between September 2015 and April 2017. Pembrolizumab was the 2nd line of treatment (after platinum-pemetrexed +/- bevacizumab) in 30 patients (63%). Twenty-eight patients (59%) had an ECOG of 0-1 at the beginning of pembrolizumab (as in the KEYNOTE-028 trial). Responses and survival outcomes are listed in Table. Investigator-reported toxicity was as follows: 15 treatment-related adverse events occurred in 14 patients (29%). Five events (10%) were G3-4 (2 patients with hepatitis, 1 with heart failure, 1 with non-cardiac chest pain and 1 with nephrotic syndrome). Seven patients (15%) discontinued treatment due to an adverse event.Table:

1615O Outcomes

total (n = 48)ECOG 0-1 (n = 28)ECOG 0-1 and 2nd line Pembro (n = 19)
ORR25% (1 CR + 11 PR)32% (1 CR + 8 PR)42% (1 CR + 7 PR)
DCR52% (incl. 13 SD)57% (incl. 7 SD)74% (incl. 6 SD)
mPFS (95% CI), months3.2 (2.6 - 4.8)3.7 (2.8 - 6.7)5.3 (3.6 - NR)
mOS (95% CI), months7.9 (6.2 - NR)9.3 (6.8 - NR)NR (8.2 - NR)
alive at 6 months (95% CI)65% (52 - 81%)72% (56 - 92%)77% (59 - 99%)
alive at 12 months (95% CI)28% (15 - 53%)43% (24 - 77%)52% (29 - 95%)

Conclusions

This is the largest reported cohort of mesothelioma patients treated with pembrolizumab thus far, and the first with any kind of anti-PD(L)1 antibody in a “real-life” setting. Compared to available second-and-beyond line treatment options, response rates and survival outcomes were promising in the unselected population, while patients with ECOG 0-1 receiving pembrolizumab in 2nd line seemed to benefit substantially. Response rates as well as the incidence of treatment-related adverse events were consistent with the KEYNOTE-028 report. Further results including subgroup analysis by PD‐L1 expression will be presented at the meeting.

Clinical trial identification

Legal entity responsible for the study

Department of Oncology, Kantonsspital Graubünden, Chur

Funding

Krebsliga Graubünden, Chur, Switzerland

Disclosure

L.A. Mauti, H. Bouchaab, S.I. Rothschild, M. Pless, R. von Moos: MSD advisory board member.

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U. Petrausch: Advisory board member for MSD.

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S. Savic Prince: Spasenija Savic Prince has received speakers honoraria from MSD.

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Y. Metaxas: MSD travel grant.

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All other authors have declared no conflicts of interest.

Disclosure

L.A. Mauti, H. Bouchaab, S.I. Rothschild, M. Pless, R. von Moos: MSD advisory board member.

U. Petrausch: Advisory board member for MSD.

S. Savic Prince: Spasenija Savic Prince has received speakers honoraria from MSD.

Y. Metaxas: MSD travel grant.

All other authors have declared no conflicts of interest.