In an adult patient with advanced lung adenocarcinoma responding to pembrolizumab (Keytruda), should treatment be discontinued after two years?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: October 8, 2026 • View editorial policy

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question

Should Pembrolizumab Be Stopped After Two Years in Responding Lung Adenocarcinoma?

Yes, discontinuing pembrolizumab after 2 years of treatment is appropriate for patients with advanced lung adenocarcinoma who have achieved disease control, as this approach does not compromise overall survival and is supported by both FDA labeling and expert consensus guidelines.

Evidence Supporting 2-Year Discontinuation

The FDA prescribing information for pembrolizumab (Keytruda) explicitly states that treatment duration in pivotal trials for metastatic NSCLC was up to 24 months 1. This 2-year cap was used in the landmark KEYNOTE-024 trial for metastatic NSCLC 2.

The IASLC expert panel (2020) provides the most direct guidance: For patients with metastatic NSCLC who received clinical benefit from immune checkpoint inhibitors, current evidence suggests 2 years as the most robustly recommended treatment duration 2. This recommendation is based on phase I data showing no differences in long-term survival benefit regardless of treatment duration, with 5-year overall survival of 15% achieved with both 2-year fixed duration and treatment until progression 2.

Real-World Evidence Confirms Safety of Discontinuation

Recent high-quality real-world data strongly supports this approach:

  • A 2026 French nationwide study of 1,480 patients who completed 2 years of pembrolizumab showed 76.9% overall survival at 48 months after the 2-year landmark, with only 26.1% requiring subsequent therapy 3

  • The 2026 Italian I-STOP study (173 patients) found no difference in overall survival between patients who discontinued versus continued ICIs at 24 months (HR 1.22,95% CI 0.50-2.95; p=0.66) 4

  • A 2023 French multicenter study of 91 patients showed no significant difference in progression-free survival between discontinuation and continuation groups 2 years after the decision (68.5% vs 64.1%; HR 1.14, p=0.77) 5

Clinical Decision Algorithm

Patients Who Should Discontinue at 2 Years:

  • Complete response on imaging (83% of French oncologists discontinue in this scenario) 6
  • Stable disease or partial response with:
    • No prior oligo-progression requiring local therapy
    • PD-L1 expression >50%
    • No brain metastases
    • ECOG performance status 0
    • Wild-type KRAS

Consider Continuation Beyond 2 Years:

  • Partial response with high-risk features:
    • PD-L1 ≤50% 4
    • Brain metastases 4
    • ECOG PS ≥1 4
    • KRAS mutations 4
    • History of oligo-progression managed with local therapy

Pre-Discontinuation Assessment:

  • PET-CT scan (recommended by 92% of French thoracic oncologists) 6
  • Brain MRI (recommended by 59%) 6
  • Document complete metabolic response if possible

Important Caveats

Rechallenge is effective if needed: Among patients who discontinued at 2 years and later progressed, rechallenge with pembrolizumab achieved a 62.5% response rate 4, and 70% clinical benefit overall, particularly in those who progress ≥1 year after stopping 2.

Immune-related adverse events can occur post-discontinuation: While uncommon (3.5% late grade 3-4 events) 4, pneumonitis has been reported up to 2.5 months after pembrolizumab cessation 7. Patients should be counseled about this risk.

The CheckMate 153 caveat: This trial in NSCLC showed continuous nivolumab beyond 1 year improved PFS compared to fixed 1-year duration (HR 0.42) 2. However, this study was underpowered for efficacy outcomes and used a 1-year (not 2-year) cutoff, making it less applicable to the 2-year question.

Practical Implementation

Gradual psychological preparation is recommended when planning discontinuation 8. Patients should understand that:

  • Stopping at 2 years does not mean treatment failure
  • Close surveillance will continue
  • Rechallenge remains an option if progression occurs
  • The goal is maximizing treatment-free survival and quality of life

Follow-up schedule post-discontinuation: CT scans every 2-4 months initially, with clinical assessment 9. The time to next treatment or death rate at 48 months after discontinuation was 49.9%, meaning approximately half of patients remain treatment-free 3.

References

Related Questions

What are the side effects of checkpoint inhibitor therapy?
What does an intrinsically bright T1 signal in the posterior pituitary that exceeds the normal bright spot indicate, and how should it be managed?
What is the appropriate treatment for an intravenous drug user presenting with meningitis signs, cerebrospinal fluid glucose of 2.5 mg/dL, lymphocytic predominance, and a CSF/serum glucose ratio greater than 4?
In an intravenous drug user with meningitis signs, CSF glucose 2.5 mg/dL, lymphocyte‑predominant pleocytosis, and a CSF‑to‑serum glucose ratio >4, what is the most likely type of meningitis?
Why does a 78-year-old male with fatty liver disease (non‑alcoholic steatohepatitis) and ascites who underwent colonoscopy and esophagogastroduodenoscopy require three platelet transfusions?
As a 30‑year‑old Black male (6'5", 320 lb) with positive antinuclear antibody, high anti‑RNP antibodies, elevated creatine kinase, diffuse muscle weakness, and recent sinus infections, what is the most likely diagnosis, what is the prognosis, and can I expect to regain strength and lead a normal life, including having a family?
What is the differential diagnosis for a patient with parkinsonism, a wide‑based gait, normal eye movements, a fine postural tremor, and normal brain imaging?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.