NCCN Guidelines on Immunotherapy Sequencing in Cancer Treatment
The NCCN guidelines do not specify a required sequence between chemotherapy and immunotherapy administration. The optimal sequencing depends on the specific cancer type, biomarker status, and clinical scenario.
General Principles of Immunotherapy Sequencing
The NCCN guidelines address immunotherapy use in various contexts, but do not mandate a specific universal sequence relative to chemotherapy. Key considerations include:
Biomarker-Driven Decision Making
- For NSCLC with actionable mutations (EGFR, ALK, ROS1, etc.), targeted therapies are recommended as initial treatment rather than immunotherapy, regardless of PD-L1 levels 1
- PD-L1 expression testing is recommended upfront to guide immunotherapy decisions when no actionable mutations are present 1
Treatment Approaches Based on Cancer Type
- For NSCLC without actionable mutations, treatment options are stratified by PD-L1 levels and may include:
- Immunotherapy alone
- Immunotherapy plus chemotherapy
- Chemotherapy followed by immunotherapy
Concurrent vs. Sequential Administration
- In some settings, such as unresectable stage III NSCLC, consolidation immunotherapy with durvalumab is recommended after chemoradiation 1
- For metastatic disease, combination chemo-immunotherapy regimens are often administered concurrently rather than sequentially 2
Timing Considerations
- When molecular testing results are pending, the NCCN panel notes that clinicians should consider holding immunotherapy for one cycle (using only platinum-based chemotherapy) until results are available 1
- This recommendation stems from concerns about potential increased toxicity when targeted therapies are used following immunotherapy 1
Clinical Implications and Safety Considerations
- The long half-life of immune checkpoint inhibitors can lead to higher rates of side effects when certain targeted therapies are used in combination with or following checkpoint inhibitors 1
- If an actionable biomarker is discovered during first-line therapy, the planned systemic therapy can be either interrupted or completed before switching to appropriate targeted therapy 1
Practical Recommendations
For patients requiring both chemotherapy and immunotherapy:
- Obtain comprehensive molecular testing and PD-L1 status before initiating therapy when possible
- If urgent treatment is needed before test results are available, consider chemotherapy alone for the first cycle
- Follow cancer-specific NCCN guidelines for the recommended regimen and sequence based on biomarker status
The decision regarding sequence should prioritize maximizing efficacy while minimizing toxicity based on the individual cancer type, biomarker profile, and patient characteristics.