Commentary: Finding the balance: The role for adjuvant immunotherapy in the neoadjuvant era

Abstract

Central MessageAdjuvant atezolizumab after chemotherapy is well tolerated in patients following bilobectomy/pneumonectomy. Surgeons' involvement as trial investigators is essential to optimize design and outcomes.See Article page XXX. Adjuvant atezolizumab after chemotherapy is well tolerated in patients following bilobectomy/pneumonectomy. Surgeons' involvement as trial investigators is essential to optimize design and outcomes. See Article page XXX. Since publication of the landmark Neoadjuvant Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Versus Chemotherapy Alone in Early Stage Non-Small Cell Lung Cancer (NSCLC) (CheckMate 816),1Forde P.M. Spicer J. Girard N. Neoadjuvant nivolumab plus chemotherapy in lung cancer. Reply.N Engl J Med. 2022; 387: 572-573Google Scholar the use of neoadjuvant immunotherapy with chemotherapy has become the standard of care for epidermal growth factor receptor-negative stage IB-IIIA non–small cell lung cancer (NSCLC) with PD-L1 expression ≥1%. This Phase 3 randomized trial assigned patients with resectable stage IB-IIIA NSCLC to receive neoadjuvant nivolumab with platinum-based chemotherapy or platinum-based chemotherapy alone, followed by surgical resection. Patients who received nivolumab with chemotherapy demonstrated a median event-free survival of 31.6 months and a pathologic complete response rate of 24% compared with median survival of 20.8 months and 2.2% pathologic complete response rate in patients receiving neoadjuvant chemotherapy alone. This survival benefit was most pronounced for patients with stage IIIA disease. Moreover, the addition of neoadjuvant nivolumab was associated with fewer cases of pneumonectomy, and radiographic downstaging occurred in 30.7% of patients who received neoadjuvant nivolumab with chemotherapy compared with 23.5% of patients who received chemotherapy alone. Adding neoadjuvant nivolumab did not increase the rate of adverse events or surgical complications at the time of resection. Before Checkmate 816, the Study to Assess Safety and Efficacy of Atezolizumab (MPDL3280A) Compared to Best Supportive Care Following Chemotherapy in Patients with Lung Cancer (IMpower010) set the standard of care for adjuvant immunotherapy with atezolizumab following platinum-based chemotherapy for patients with stage II-IIIA NSCLC following complete surgical resection, demonstrating improved survival in patients with PD-L1 expression in at least 1% of tumor cells.2Felip E. Altorki N. Zhou C. Csöszi T. Vynnychenko I. Goloborodko O. et al.Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial.Lancet. 2021; 398: 1344-1357Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar Lee and colleagues3Lee J.M. Vallieres E. Ding B. Johnson A. Bhagwakar J. Rashidi S. et al.Safety of adjuvant atezolizumab after pneumonectomy/bilobectomy in stage II-IIIA non-small cell lung cancer in the randomized phase III IMpower010 trial.J Thorac Cardiovasc Surg. 2023; (XXX:XXX)Abstract Full Text PDF Google Scholar present results from this trial evaluating safety and tolerance based on extent of surgical resection, comparing patients undergoing bilobectomy or pneumonectomy with patients who underwent lobectomy or sleeve lobectomy. The authors report similar rates of atezolizumab discontinuation (32% vs 35%) and adverse events (21% vs 23%) in both groups. The authors also report similar time to initiation of chemotherapy and adjuvant immunotherapy following surgery across resection groups. These results support adjuvant immunotherapy with chemotherapy as a safe approach for patients who have undergone extended pulmonary resections. The outstanding question remains: Is the optimal timing of immunotherapy in the adjuvant or neoadjuvant setting? In the absence of clinical trial data directly comparing these approaches head to head, we are tasked with how to integrate and apply these data in real-world clinical settings. A neoadjuvant approach to immunotherapy with chemotherapy seems preferable, with the goal of downstaging tumors and decreasing the extent of pulmonary resection, ideally decreasing the need for pneumonectomies or bilobectomies in patients who respond well to treatment. However, the role for adjuvant immunotherapy remains relevant for patients with unanticipated nodal involvement and in patients who are less likely to tolerate an aggressive neoadjuvant approach due to frailty or other comorbidities. Additional outstanding questions include, What is the optimal anti-PD-L1 agent in each setting? And, what PD-L1 expression level threshold should influence the decision to initiate anti-PD-L1 treatment? The ongoing involvement of thoracic surgeons as key investigators in these trials is critical to optimize disease-free survival, surgical outcomes, and lung preservation for patients with resectable NSCLC. Safety of adjuvant atezolizumab after pneumonectomy/bilobectomy in stage II-IIIA non–small cell lung cancer in the randomized phase III IMpower010 trialThe Journal of Thoracic and Cardiovascular SurgeryPreviewAdjuvant atezolizumab is a standard of care after chemotherapy in completely resected stage II-IIIA programmed death ligand-1 tumor cell 1% or greater non–small cell lung cancer based on results from the phase III IMpower010 study. We explored the safety and tolerability of adjuvant atezolizumab by surgery type in IMpower010. Full-Text PDF Open Access