Pembrolizumab as second or further line treatment in relapsed malignant pleural mesothelioma: A Swiss registry

Abstract

Background: Available 2nd line chemotherapies for relapsed malignant pleural meso-thelioma (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 pem-brolizumab 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 pem-brolizumab for relapsed MPM between September 2015 and April 2017. Pembrolizumab was the 2nd line of treatment (after platinum-pemetrexed þ/-bevaci-zumab) 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 ad-verse event. 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, re-sponse rates and survival outcomes were promising in the unselected population, while patients with ECOG 0-1 receiving pembrolizumab in 2nd line seemed to benefit sub-stantially. 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. Table: 1615O Outcomes total (n ¼ 48) ECOG 0-1 (n ¼ 28) ECOG 0-1 and 2nd line Pembro (n ¼ 19) ORR 25% (1 CR þ 11 PR) 32% (1 CR þ 8 PR) 42% (1 CR þ 7 PR) DCR 52% (incl. 13 SD) 57% (incl. 7 SD) 74% (incl. 6 SD) mPFS (95% CI), months 3.2 (2.6 -4.8) 3.7 (2.8 -6.7) 5.3 (3.6 -NR) mOS (95% CI), months 7.9 (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%)