The Efficacy and Safety of Neoadjuvant Immunotherapy in Patients with Non-Small Cell Lung Cancer

The advent of immunotherapy has transformed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC). In the past few years, several studies have investigated the potential role of immune checkpoint inhibitors (ICIs) in resectable and unresectable locally advanced disease, achieving remarkable results that led to their approval in clinical practice. However, there is limited evidence on immunotherapy rechallenge after recurrence, with the majority of available knowledge coming from retrospective studies which involve heavily pretreated patients with advanced NSCLC. The recent introduction in the curative setting and the potential regulatory restrictions raise questions about the optimal choice of first-line and subsequent therapies for patients with systemic relapse. The role of immunotherapy readministration in this new scenario needs to be clarified, as well as the identification of patients for whom it is more appropriate, including clinical characteristics, duration of response, switching to other ICIs, reasons for discontinuation and immune-related toxicity. Here, we review literature on rechallenge with immunotherapy, including efficacy, safety profile and potential predictive factors of response.

Section: Discussionmentioning

confidence: 97%

Retreatment with Immune Checkpoint Inhibitors in the New Scenario of Immunotherapy in Non-Small Cell Lung Cancer

Rossi,

Masini,

Finocchiaro

et al. 2024

“…A trend towards lower pneumonectomy rates was observed, however, without being statistically significant. Lastly, all-grade AEs were similar in both chemoimmunotherapy and chemotherapy groups (96.2% vs. 95.8%, respectively), although a noted increase in grade 3-4 AEs was observed in patients who received chemoimmunotherapy (45.1% vs. 41.7% for chemotherapy alone) and must therefore be mentioned (Guven et al [53]).…”

Section: Perioperative Immunotherapymentioning

confidence: 95%

“…A subgroup analysis of the latter demonstrated benefit among this patient population, with HR at 0.43. These data, alongside pending results from ongoing studies, could redefine resectability criteria and include more patients as feasible for surgery [53,75,83].…”

Section: Conclusion and Future Challengesmentioning

confidence: 96%

“…A second question that remains unanswered is whether patients that fail to achieve pCR or MPR do actually benefit from continuing on the same immunotherapy protocol and whether treatment escalation attempts should be made, perhaps with the addition of another ICI agent-CTLA-4, LAG-3, etc.-or ADCs to achieve better therapeutic outcomes. To date, there is no strong evidentiary support that response to neoadjuvant treatment should further guide adjuvant treatment decisions [53,75,83,84].…”

Section: Conclusion and Future Challengesmentioning

confidence: 99%

See 1 more Smart Citation

Neoadjuvant and Adjuvant Immunotherapy in Resectable NSCLC

Bogatsa,

Lazaridis,

Stivanaki

et al. 2024

Non-small cell lung cancer, even when diagnosed in early stages, has been linked with poor survival rates and distant recurrence patterns. Novel therapeutic approaches harnessing the immune system have been implemented in early stages, following the designated steps of advanced NSCLC treatment strategies. Immune-checkpoint inhibitor (ICI) regimens as monotherapy, combinational, or alongside chemotherapy have been intensely investigated as adjuvant, neoadjuvant, and, more recently, perioperative therapeutic strategies, representing pivotal milestones in the evolution of early lung cancer management while holding great potential for the future. The subject of current ongoing research is optimizing treatment outcomes for patient subsets with different needs and identifying biomarkers that could be predictive of response while translating the trials’ endpoints to survival rates. The aim of this review is to discuss all current treatment options with the pros and cons of each, persistent challenges, and future perspectives on immunotherapy as illuminating the path to a new era for resectable NSCLC.

“…Recent data have been evaluated in a meta-analysis, showing that NA/perioperative immunochemotherapy (ICI-chemo) results in significant improvement in pathological complete response (pCR) rate (risk ratio (RR): 5.66, 95% CI 3. 48-9.18), event-free survival (EFS), OS, major pathological response (MPR) rate, and R0 resection rate compared to chemotherapy alone [11,12]. NA nivolumab with chemotherapy is now approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) in resectable, stage IB-IIIA (American Joint Committee on Cancer (AJCC), 7th Edition) NSCLC, based on the CheckMate 816 trial.…”

Section: Introductionmentioning

confidence: 99%

An Updated Review of Management of Resectable Stage III NSCLC in the Era of Neoadjuvant Immunotherapy

Verma,

Breadner,

Mittal

et al. 2024

Immune-checkpoint inhibitors (ICIs) have an established role in the treatment of locally advanced and metastatic non-small cell lung cancer (NSCLC). ICIs have now entered the paradigm of early-stage NSCLC. The recent evidence shows that the addition of ICI to neoadjuvant chemotherapy improves the pathological complete response (pCR) rate and survival rate in early-stage resectable NSCLC and is now a standard of care option in this setting. In this regard, stage III NSCLC merits special consideration, as it is heterogenous and requires a multidisciplinary approach to management. As the neoadjuvant approach is being adopted widely, new challenges have emerged and the boundaries for resectability are being re-examined. Consequently, it is ever more important to carefully individualize the treatment strategy for each patient with resectable stage III NSCLC. In this review, we discuss the recent literature in this field with particular focus on evolving definitions of resectability, T4 disease, N2 disease (single and multi-station), and nodal downstaging. We also highlight the controversy around adjuvant treatment in this setting and discuss the selection of patients for adjuvant treatment, options of salvage, and next line treatment in cases of progression on/after neoadjuvant treatment or after R2 resection. We will conclude with a brief discussion of predictive biomarkers, predictive models, ongoing studies, and directions for future research in this space.