Surgical outcomes from the phase 3 CheckMate 816 trial: Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo alone as neoadjuvant treatment for patients with resectable non-small cell lung cancer (NSCLC).

Abstract

8503 Background: CheckMate 816 (NCT02998528) is a randomized phase 3 study of neoadjuvant NIVO + chemo vs chemo in resectable NSCLC. The study met its first primary endpoint, demonstrating significantly improved pathological complete response (pCR) with neoadjuvant NIVO + chemo. Here we report key surgical outcomes from the study. Methods: Adults with stage IB (≥ 4 cm)–IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS ≤ 1, and no known EGFR/ ALK alterations were randomized to NIVO 360 mg + platinum-doublet chemo Q3W or chemo Q3W for 3 cycles (n = 179 each). Definitive surgery was to be performed within 6 weeks of treatment. Primary endpoints are pCR (defined as 0% viable tumor cells in lung and lymph nodes) and event-free survival; both are evaluated by blinded independent review. Feasibility of surgery and surgery-related adverse events (AEs) are exploratory endpoints. Results: Baseline characteristics were comparable between arms; 64% of patients (pts) were stage IIIA. Definitive surgery rates were 83% with NIVO + chemo (n = 149) vs 75% with chemo (n = 135). Reasons for cancelled surgery were disease progression (12 and 17 pts, respectively), AEs (2 pts/arm), or other scenarios (14 and 19 pts, respectively; including pt refusal, unresectability, poor lung function). Minimally invasive surgery rates were 30% and 22%, and conversion from minimally invasive to open surgery rates were 11% and 16% for NIVO + chemo and chemo, respectively. Lobectomy was performed in 77% vs 61% of pts, and pneumonectomy in 17% and 25% for NIVO + chemo vs chemo, respectively. AEs were responsible for delays of surgery in 6 pts in the NIVO + chemo arm and 9 pts in the chemo arm. An R0 resection was achieved in 83% vs 78% of pts and median residual viable tumor (RVT) cells in the primary tumor bed were 10% vs 74% for NIVO + chemo vs chemo. There was no increase in median (Q1, Q3) duration of surgery and length of hospitalization between NIVO + chemo vs chemo (184 [130, 252] vs 217 [150, 283] min; and 10.0 [7, 14] vs 10.0 [7, 14] days, respectively). Any-grade and grade 3–4 surgery-related AEs were reported in 41% vs 47% and 11% vs 15% of the NIVO + chemo vs chemo arms, respectively. Grade 5 surgery-related AEs were reported in 2 vs 0 pts in the NIVO + chemo vs chemo arms; 0 vs 3 pts died due to treatment-related AEs, respectively. Conclusions: In CheckMate 816, neoadjuvant NIVO + chemo did not impede the feasibility and timing of surgery, nor the extent or completeness of resection vs chemo alone; treatment was tolerable and did not increase surgical complications. NIVO + chemo led to increased depth of pathological response. The surgical outcome data from CheckMate 816 along with significant improvement in pCR support NIVO + chemo as a potential neoadjuvant option for patients with stage IB to IIIA resectable NSCLC. Clinical trial information: NCT02998528.

Exploring the Evolving Scope of Neoadjuvant Immunotherapy in NSCLC

“…The observed improvement in pCR was observed across all major subgroups including disease stage (IB/II [26.2% vs. 4.8%]; ≥IIIA [23.0% vs. 0.9%]) and PD-L1 status (<1% [16.7% vs. 2.6%]; ≥1% [32.6% vs. 2.2%]). MPR rates were also significantly improved with nivolumab + chemotherapy (36.9% vs. 8.9%) [38,39].…”

Salvage surgery following immuno-chemo-radiotherapy for advanced non-small cell lung cancer

“…Immuno-chemotherapy has become a standard treatment of care for unresectable NSCLC with no driver-gene alteration [ 7 ], and also may be useful as neoadjuvant treatment prior to surgery for resectable NSCLC [ 3 – 6 ]. A randomized controlled trial (CheckMate 816) comparing neoadjuvant immuno-chemotherapy with chemotherapy showed that the addition of immunotherapy did not increase incidence of postoperative adverse events.…”

“…Salvage surgery following definitive radiotherapy or systemic treatment has been increasingly adopted as a feasible treatment option in selected patients with advanced non-small cell lung cancer (NSCLC) which had been initially diagnosed as unresectable disease [ 1 , 2 ]. Recent clinical trials of neoadjuvant treatment for resectable NSCLC have revealed that the addition of immuno-therapy using an antibody against programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) to platinum-based chemotherapy (immuno-chemotherapy) may provide superior pathologic response and superior survival benefit over chemotherapy alone [ 3 – 6 ]. To further improve the therapeutic efficacy, immuno-chemotherapy with concurrent radiotherapy (cICRT) may be a promising treatment option.…”

Neoadjuvant and Adjuvant Immunotherapy in Non-Small Cell Lung Cancer—Clinical Trials Experience

“…Although R0 resection was achieved in the same percentage of patients from both groups, the median residual viable tumor (RVT) cells in the primary tumor bed were 10% in patients treated with combination therapy vs. 74% in patients who received chemotherapy alone. The data from CheckMate 816 support nivolumab plus chemotherapy as a potential neoadjuvant option for patients with stage IB to IIIA resectable NSCLC [18].…”