Systemic treatment options for non-small cell lung cancer after failure of previous immune checkpoint inhibitors: a
Kang Wang1, Zhenxue Fu2, Guanxing Sun1
1Department of Oncology, Zaozhuang Municipal Hospital, Zaozhuang, 277100, China.
Background:
Although immune checkpoint inhibitors (ICIs) have brought survival benefits to non-small cell lung cancer (NSCLC), disease progression still occurs, and there is no consensus on the treatment options for these patients. We designed a network meta-analysis (NMA) to evaluate systemic treatment options for NSCLC after failure of ICIs.
Methods:
PubMed, Embase, Web of Science and Cochrane Library databases were searched, then literature screening was followed by NMA. We included all Phase II and III randomized controlled trials (RCTs). Progression-free survival (PFS) and overall survival (OS) used hazard ratio (HR) for evaluation. Objective response rate (ORR) and adverse events (AEs) used odds ratio (OR) and relative risk (RR) effect sizes, respectively. R software was applied to compare the Bayesian NMA results.
Results:
We finally included 6 studies. 1322 patients received ICI plus Chemotherapy (ICI + Chemo), ICI plus Anti-angiogenic monoclonal antibody (ICI + Antiangio-Ab), ICI plus Tyrosine kinase inhibitor (ICI + TKI), Tyrosine kinase inhibitor plus Chemotherapy (TKI + Chemo), Standard of Care (SOC), Chemotherapy (Chemo). TKI + Chemo is associated with longer PFS, higher ORR (surface under cumulative ranking curve [SUCRA], 99.7%, 88.2%), ICI + TKI achieved the longest OS (SUCRA, 82.7%). ICI + Antiangio-Ab was granted the highest safety rating for adverse events (AEs) of any grade, AEs greater than or equal to grade 3 and AEs of any grade leading to discontinuation of treatment (SUCRA, 95%, 82%, 93%).
Conclusions:
For NSCLC after failure of ICIs, TKI + Chemo was associated with longer PFS and higher ORR, while ICI + TKI was associated with the longest OS. In terms of safety, ICI + Antiangio-Ab was the highest.
Insights
For non-small cell lung cancer (NSCLC) progressing after immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitor plus chemotherapy (TKI+Chemo) improved progression-free survival and response rates. ICI plus TKI (ICI+TKI) offered the longest overall survival, while ICI plus anti-angiogenic antibody (ICI+Antiangio-Ab) showed the best safety profile.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- Immune checkpoint inhibitors (ICIs) have improved survival in non-small cell lung cancer (NSCLC).
- Optimal systemic treatment strategies for NSCLC patients experiencing disease progression after ICI therapy remain undefined.
- This study addresses the need for evidence-based treatment recommendations in advanced NSCLC post-ICI failure.
Purpose of the Study:
- To conduct a network meta-analysis (NMA) comparing various systemic treatments for NSCLC following ICI failure.
- To evaluate efficacy outcomes including progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).
- To assess safety profiles, specifically adverse events (AEs) across different treatment regimens.
Main Methods:
- A systematic literature search was performed across PubMed, Embase, Web of Science, and Cochrane Library databases.
- Included were Phase II and III randomized controlled trials (RCTs) comparing systemic therapies post-ICI failure.
- Bayesian network meta-analysis was employed using R software to compare treatments based on hazard ratios (HR) for PFS and OS, and odds ratios (OR) for ORR, and relative risks (RR) for AEs.
Main Results:
- Six studies involving 1322 patients were analyzed, comparing treatments such as ICI+Chemotherapy, ICI+Anti-angiogenic monoclonal antibody (ICI+Antiangio-Ab), ICI+Tyrosine kinase inhibitor (ICI+TKI), Tyrosine kinase inhibitor+Chemotherapy (TKI+Chemo), Standard of Care (SOC), and Chemotherapy (Chemo).
- TKI+Chemo demonstrated superior PFS and ORR (SUCRA 99.7% and 88.2%, respectively).
- ICI+TKI achieved the longest OS (SUCRA 82.7%), while ICI+Antiangio-Ab exhibited the best safety profile regarding AEs of any grade, grade 3+, and treatment discontinuation (SUCRA 95%, 82%, and 93%, respectively).
Conclusions:
- For NSCLC patients who progressed on ICIs, TKI+Chemo is recommended for improved PFS and ORR.
- ICI+TKI is associated with the longest OS, offering a survival benefit.
- ICI+Antiangio-Ab provides the most favorable safety profile, crucial for patient tolerability and treatment adherence.
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