Should Immunotherapy Be Limited to 2 Years in Lung Cancer Patients Who Benefit?

Introduced with their first FDA approval in 2011, “immune checkpoint inhibitor” immunotherapies have transformed oncology. 85% of lung cancers are non-small cell lung cancer (NSCLC). In recent years, some patients with long-term responses have continued immunotherapy for more than 2 years. Yet the best available evidence suggests that treatment beyond 2 years probably offers no survival advantage. This highlights a mismatch between practice and evidence. Why, then, do many oncologists recommend continuing for more than 2 years? This article explores the question and its importance.

4 Key Points:

1. Long-Term Immunotherapy: Many people with NSCLC continue immunotherapy beyond 2 years, although current data suggest no additional survival benefit after this period.
2. Clinical Decisions and Uncertainty: Doctors and patients hesitate to stop a treatment that appears to be working. This may reflect a tendency towards overtreatment even when the situation is uncertain.
3. Gaps in Research: Most major trials of first-line immunotherapy for NSCLC limit treatment to 2 years, and prospective clinical data on when it should stop are lacking.
4. Potential Future Strategies: Rather than continuing immunotherapy indefinitely, future strategies may aim to maintain the patient’s “best possible response”, adding interventions when needed, such as stereotactic body radiotherapy or radiological ablation.

Important Studies and Findings

• Checkmate 153 Trial: Checkmate 153, a phase IIIb/IV trial assessing nivolumab in previously treated advanced NSCLC, published results in 2020. Patients receiving a fixed 1-year course had shorter progression-free and overall survival than those continuing treatment indefinitely.
• KEYNOTE-024 Trial: stage 4 NSCLC patients with high tumour PD-L1 positivity: more than 45% survived for 5 years without further treatment or progression after receiving pembrolizumab for 2 years.
• KEYNOTE-407 Trial: Similar 5-year survival results were seen in advanced squamous NSCLC, regardless of PD-L1 status, among patients completing 2 years of chemotherapy plus pembrolizumab followed by maintenance pembrolizumab.
• JAMA Oncology published a retrospective cohort analysis by Lova Sun and colleagues assessing overall survival in advanced NSCLC. Of 14,406 people starting first-line immunotherapy, the analysis focused on 706 who completed 2 years of treatment. A key finding was that 84% chose to continue rather than stop after 2 years. This suggests a tendency towards overtreatment. Nevertheless, overall survival did not differ significantly between those treated for approximately 2 years (760 days) and those treated longer: 79% and 81%, respectively. The study emphasises that stopping after 2 years offers the same survival benefit as prolonged treatment, alongside less risk of adverse effects, less treatment time and lower healthcare costs.

Conclusion

Without more definitive evidence on when to stop, many oncologists continue indefinitely as long as patients tolerate treatment and the disease does not progress.

In future, the aim may shift from indefinite immunotherapy to maintaining the patient’s “best possible response”, adding an intervention when necessary.

Many people with long-term disease control may not be cured in the traditional sense, but continued care can keep their cancer controlled for years or even decades.