TY - JOUR
T1 - Rare targetable drivers (RTDs) in non-small cell lung cancer (NSCLC)
T2 - Outcomes with immune check-point inhibitors (ICPi)
AU - Dudnik, Elizabeth
AU - Bshara, Elias
AU - Grubstein, Ahuva
AU - Fridel, Ludmila
AU - Shochat, Tzippy
AU - Roisman, Laila C.
AU - Ilouze, Maya
AU - Rozenblum, Anna Belilovski
AU - Geva, Smadar
AU - Zer, Alona
AU - Rotem, Ofer
AU - Allen, Aaron M.
AU - Peled, Nir
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/10
Y1 - 2018/10
N2 - Objectives: Efficacy of immune check-point inhibitors (ICPi) in NSCLC with rare targetable drivers (RTDs) is largely unknown. Materials and Methods: Consecutive patients with NSCLC and RTDs (non-EGFR/ALK, n-82) were selected from the Davidoff Cancer Center database. ORR, PFS, OS with ICPi, OS since advanced disease diagnosis, TMB, MSI, and PD-L1 expression were analyzed; uni- and multivariate PFS and OS analyses were done. OS with ICPi was compared between the RTD cohort and the non-selected NSCLC cohort (n-278). Results: Of 50 tumors tested, 32%, 38%, and 30% were associated with ≥50%, 1–49% and <1% PD-L1 expression, respectively. Median TMB (n-48) comprised 4 muts/Mb (0–57); TMB ≥ 10 muts/Mb was seen in 19% of tumors. Both TMB and PD-L1 expression varied across different RTDs. All the 47 tumors were MSI stable. ORR with ICPi (n-44) was 16%, median PFS was 3.2 months (95% CI, 2.6–5.0), median OS was 16.2 months (95% CI, 8.4-NR). No correlation was seen between OS with ICPi and PD-L1 expression (p > 0.4), TMB (p > 0.8), or RTD type (p > 0.3). In the multivariate analysis, ECOG PS (p-0.005), targeted agents exposure (p-0.005), and ICPi exposure (p-0.04) were the only variables which correlated with OS since advanced disease diagnosis. Median OS since advanced disease diagnosis comprised 32 months (95% CI, 19.9–44.9) and 13 months (95% CI, 6.6–15.9) for patients who were and were not exposed to ICPi, respectively (log-rank test-6.3; p-0.01). In the inter-cohort comparison, for patients matched for ECOG PS (0/1), median OS with ICPi comprised 17.5 months (95% CI, 8.1-NR) and 8.6 months (95% CI, 6.7-NR) for RTD and non-selected patients, respectively (log-rank test-2.4, p-0.1). Conclusion: In NSCLC with RTD, ICPi have favorable efficacy and independent impact on OS. NSCLC with RTD is associated with MSI stable status and variable levels of PD-L1 expression and TMB; their predictive value remains to be determined.
AB - Objectives: Efficacy of immune check-point inhibitors (ICPi) in NSCLC with rare targetable drivers (RTDs) is largely unknown. Materials and Methods: Consecutive patients with NSCLC and RTDs (non-EGFR/ALK, n-82) were selected from the Davidoff Cancer Center database. ORR, PFS, OS with ICPi, OS since advanced disease diagnosis, TMB, MSI, and PD-L1 expression were analyzed; uni- and multivariate PFS and OS analyses were done. OS with ICPi was compared between the RTD cohort and the non-selected NSCLC cohort (n-278). Results: Of 50 tumors tested, 32%, 38%, and 30% were associated with ≥50%, 1–49% and <1% PD-L1 expression, respectively. Median TMB (n-48) comprised 4 muts/Mb (0–57); TMB ≥ 10 muts/Mb was seen in 19% of tumors. Both TMB and PD-L1 expression varied across different RTDs. All the 47 tumors were MSI stable. ORR with ICPi (n-44) was 16%, median PFS was 3.2 months (95% CI, 2.6–5.0), median OS was 16.2 months (95% CI, 8.4-NR). No correlation was seen between OS with ICPi and PD-L1 expression (p > 0.4), TMB (p > 0.8), or RTD type (p > 0.3). In the multivariate analysis, ECOG PS (p-0.005), targeted agents exposure (p-0.005), and ICPi exposure (p-0.04) were the only variables which correlated with OS since advanced disease diagnosis. Median OS since advanced disease diagnosis comprised 32 months (95% CI, 19.9–44.9) and 13 months (95% CI, 6.6–15.9) for patients who were and were not exposed to ICPi, respectively (log-rank test-6.3; p-0.01). In the inter-cohort comparison, for patients matched for ECOG PS (0/1), median OS with ICPi comprised 17.5 months (95% CI, 8.1-NR) and 8.6 months (95% CI, 6.7-NR) for RTD and non-selected patients, respectively (log-rank test-2.4, p-0.1). Conclusion: In NSCLC with RTD, ICPi have favorable efficacy and independent impact on OS. NSCLC with RTD is associated with MSI stable status and variable levels of PD-L1 expression and TMB; their predictive value remains to be determined.
KW - Immunotherapy
KW - Lung cancer
KW - Mutation
KW - PD-1
KW - PD-L1
KW - Tumor mutational burden
UR - http://www.scopus.com/inward/record.url?scp=85051129345&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2018.07.044
DO - 10.1016/j.lungcan.2018.07.044
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 30268448
AN - SCOPUS:85051129345
SN - 0169-5002
VL - 124
SP - 117
EP - 124
JO - Lung Cancer
JF - Lung Cancer
ER -
