OA11.01 Neoadjuvant Pembrolizumab for Early Stage Non-Small Cell Lung Cancer

Abstract

Neoadjuvant immune checkpoint inhibitor treatment is a promising approach for resectable cancer. The optimal treatment regimen has yet to be determined. This study was initially reported at the ESMO annual meeting 2018 and at the ASCO 2019 annual meeting. We currently report the final analysis for safety, the primary endpoint of the study, and updated efficacy results. We have conducted a phase I, investigator-initiated single-center study, to examine the safety of neoadjuvant pembrolizumab for stage I-II (TNM v7) resectable NSCLC, to identify the recommended phase II dose/schedule (RP2D/S) and to evaluate efficacy by remaining viable cells (10% or less defined as a major pathologic response, MPR). The study cohorts differed in number of pembrolizumab doses, and in treatment initiation-to-surgery intervals. Exploratory analyses were done to evaluate factors possibly correlated with MPR. 26 patients initiated treatment on the study. Median age: 69 (range 51-79) years, 54% men, smoking status: 62%/31%/8% current/past/never. ECOG PS: 1/0 in 85%/15%. Histology: adenocarcinoma/squamous/adeno-squamous/NSCLC in 50%/42%/4%/4%. No DLT and no grade 5 TRAE occurred. Two patients (8%, 95% C.I 0-18%) had grade 3-4 TRAE; one patient had both grade 3 myositis and myocarditis (causing surgery deferral) and one patient had both grade 3 encephalitis and hepatitis (following surgery, 124 and 171 days respectively from pembrolizumab initiation). Median change in tumor diameter radiologically was -5% (range, -43% to 70%). By RECIST, one patient (4%; 95% C.I. 0-11%) had PR, 21 patients (81%; 95% C.I. 66-96%) had SD, two patients (8%; 95% C.I. 0-18%) had PD and two patients were non-evaluable. One patient refused surgery after treatment and one patient had a non-treatment-related myocardial infarct leading to surgery deferral. Pathologically, 7 patients (27%, 95% C.I 10-44%) achieved a MPR, 3 (12%, 95% C.I 1-24%) achieved pCR. Patients with MPR had longer treatment-surgery interval (Table). At a median follow up of 23 months (95% CI 13-32), 2 patients of the 26 treated patients (8%, 95% C.I 0-18) died, one of them with no evidence of disease. One of the 23 operated patients (4%, 95% C.I. 0-13%) had disease recurrence.TableComparison of patients that underwent surgery (n=23) with and without MPRParameterMPR achievedNo MPRP valueN716Age - median (min-max) years71 (66-73)64 (51-79)0.138Male - n (%)6 (86%)6 (38%)0.069Smoking status – n (%)1.000Yes5 (71)10 (63)Past2 (29)5 (31)Never0 (0)1 (6)Pathology – n (%)1.000Adenocarcinoma4 (57)7 (44)Squamous3 (43)7 (44)Adeno-Squamous0 (0)1 (6)NSCLC0 (0)1 (6)Tumor size - Avg (min-max) mm32 (24-48)33 (11-74)0.822T stage - n (%)T1b3 (18)T1c4 (57)6 (35)T2a2 (29)3 (18)T2b1 (14)2 (12)T31 (6)T41 (6)N stage - n (%)0.416N 07 (100)14 (88)N 10 (0)2 (12)PDL1 - median (min-max) %1 (0-65)2 (0-85)0.632Treatment initiation-Surgery interval - median (min-max) days43 (38-52)36 (23-62)0.043 Open table in a new tab Neoadjuvant pembrolizumab for early NSCLC achieved a 27% rate of MPR, a 12% rate of pCR, with 8% rate of grade 3-4 TRAE. Two doses of neoadjuvant pembrolizumab at a three week interval, followed by surgery two weeks later, is the RP2D/S. Longer interval from treatment to surgery was associated with higher rate of MPR. Correlative studies are ongoing.