Details

Autor(en) / Beteiligte

• Sabari, J.K.
• Leonardi, G.C.
• Shu, C.A.
• Umeton, R.
• Montecalvo, J.
• Ni, A.
• Chen, R.
• Dienstag, J.
• Mrad, C.
• Bergagnini, I.
• Lai, W.V.
• Offin, M.
• Arbour, K.C.
• Plodkowski, A.J.
• Halpenny, D.F.
• Paik, P.K.
• Li, B.T.
• Riely, G.J.
• Kris, M.G.
• Rudin, C.M.
• Sholl, L.M.
• Nishino, M.
• Hellmann, M.D.
• Rekhtman, N.
• Awad, M.M.
• Drilon, A.

Titel

PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers

Ist Teil von

• Annals of oncology, 2018-10, Vol.29 (10), p.2085-2091

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• MET exon 14 alterations are actionable oncogenic drivers. Durable responses to MET inhibitors are observed in patients with advanced MET exon 14-altered lung cancers in prospective trials. In contrast, the activity of immunotherapy, PD-L1 expression and tumor mutational burden (TMB) of these tumors and are not well characterized. Patients with MET exon 14-altered lung cancers of any stage treated at two academic institutions were identified. A review of clinicopathologic and molecular features, and an analysis of response to single-agent or combination immune checkpoint inhibition were conducted. PD-L1 immunohistochemistry was carried out and TMB was calculated by estimation from targeted next-generation sequencing panels. We identified 147 patients with MET exon 14-altered lung cancers. PD-L1 expression of 0%, 1%–49%, and ≥50% were 37%, 22%, and 41%, respectively, in 111 evaluable tumor samples. The median TMB of MET exon 14-altered lung cancers was lower than that of unselected non-small-cell lung cancers (NSCLCs) in both independently evaluated cohorts: 3.8 versus 5.7 mutations/megabase (P<0.001, n=78 versus 1769, cohort A), and 7.3 versus 11.8 mutations/megabase (P<0.001, n=62 versus 1100, cohort B). There was no association between PD-L1 expression and TMB (Spearman’s rho=0.18, P=0.069). In response-evaluable patients (n=24), the objective response rate was 17% (95% CI 6% to 36%) and the median progression-free survival was 1.9months (95% CI 1.7–2.7). Responses were not enriched in tumors with PD-L1 expression ≥50% nor high TMB. A substantial proportion of MET exon 14-altered lung cancers express PD-L1, but the median TMB is lower compared with unselected NSCLCs. Occasional responses to PD-1 blockade can be achieved, but overall clinical efficacy is modest.