P2.04-89 Neoadjuvant Pembrolizumab in Early Stage Non-Small Cell Lung Cancer (NSCLC): Toxicity, Efficacy, and Surgical Outcomes

Abstract

Background: Pembrolizumab is a programmed death receptor-1 masking antibody approved for advanced NSCLC in program death receptor ligand-1 high tumors, and in chemotherapy combinations. This trial studies the effect of neoadjuvant pembrolizumab on surgical tolerability (primary endpoint), tumor response, side effects, and immune biomarkers in blood and tumor. Method: Baseline PET/CT, brain imaging, histologic diagnosis NSCLC, and surgical consultation were required for eligibility. Patients with stage T >3 cm and N0, N1, or resectable N2 NSCLC received neoadjuvant pembrolizumab 200 mg every 21 days 2 cycles prior to pre-operative chest CT scan followed by standard surgery. Adjuvant chemotherapy was strongly encouraged but not required. After completion of standard chemotherapy, 4 cycles of adjuvant pembrolizumab 200 mg every 21 days was offered. Blood for immune profiling of circulating immune cells was collected at baseline, after cycle 2 pembrolizumab, after surgery, and after adjuvant pembrolizumab. Excess tumor was disaggregated for tumor infiltrating lymphocytes, regulatory immune cells, and tumor cells, and viably stored for later analysis. We report clinical outcomes of tumor response and surgical outcomes.

Expert consensus on neoadjuvant immunotherapy for non-small cell lung cancer

“…No data from large-scale phase III clinical trials of neoadjuvant immunotherapy are yet available, but the results of several phase II clinical trials showed that neoadjuvant immunotherapy may play an important role in the multi-disciplinary management of early-stage NSCLC (26)(27)(28)(29)(30)(31). The results of trials of neoadjuvant immunotherapy were summarized in Table 1.…”

“…This monotherapy was also found to be safe and efficacious. The MPR rate was 28%, and up to 80% of patients had pathological remission ≥50% (28). The LCMC3 phase II clinical study of PD-L1 inhibitors showed that in patients with stage IB-IIIA NSCLC (plus selected stage IIIB patients), two-cycle atezolizumab monotherapy was found to be well-tolerated and have promising outcomes.…”

“…At present, the effects of neoadjuvant immunotherapy on early-stage NSCLC are known only from phase I/II clinical trials, without large-scale phase III trials. The neoadjuvant single agent immunotherapy in CheckMate159, LCMC3, and TOP1501, was performed for two cycles, and surgery was performed 28-56 days after the first cycle (26)(27)(28). Neoadjuvant immunotherapy combined with chemotherapy (NADIM: phase II with N=51) or combination of two checkpoint inhibitors (PD-1 and CTLA-4) (NEOSTAR: phase II with N=44) was performed for three to four cycles, and surgery was performed 3-7 weeks after the end of the neoadjuvant therapy (43).…”

Canakinumab with and Without Pembrolizumab in Patients with Resectable Non-Small-Cell Lung Cancer: CANOPY-N Study Design

“…Recent clinical studies have published results of first analyses of the safety and feasibility of the use of neoadjuvant anti-PD-1/PD-L1 inhibitors in some patients with NSCLC (Table 1) [20][21][22][23][24][25][26][27]. In a pilot Phase II study of 21 eligible patients with surgically resectable NSCLC (stage I, II or IIIA) conducted by Forde et al, nivolumab monotherapy administered as neoadjuvant treatment (3 mg/kg for two cycles during 4 weeks before surgery) did not delay surgery and induced MPR in 45% of resected tumors (9/20).…”

“…Nivolumab-related side effects of any grade occurred in 23% (5/22) of patients [20]. In a different Phase II trial investigating toxicity, efficacy and surgical outcomes of neoadjuvant pembrolizumab (200 mg for two cycles prior to surgery) in 30 patients with resectable NSCLC, at least two pathological complete responses (pCRs) were observed [21]. In a single-arm Phase II trial, Shu et al reported that 57% (17/30) and 33% (10/30) of patients with stage IB-IIIA NSCLC treated with two cycles of neoadjuvant atezolizumab (1200 mg) in combination with chemotherapy (nab-paclitaxel, 100 mg/m 2 and carboplatin, 5 mg/ml per min) achieved MPR and pCR, respectively.…”