Lung cancer is one of the most commonly diagnosed cancers and has historically been among the most difficult to treat. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Over the past decade, pembrolizumab has fundamentally changed the treatment landscape - producing survival improvements that were not previously achievable.
The role of PD-L1 in NSCLC
In NSCLC, PD-L1 expression is measured using the Tumour Proportion Score (TPS). A TPS of 50% or higher identifies patients most likely to benefit from pembrolizumab monotherapy in the first-line setting - that is, as the first treatment given after diagnosis of advanced or metastatic disease. Patients with TPS between 1% and 49% may benefit from pembrolizumab in combination with chemotherapy. Patients with no detectable PD-L1 expression are generally not offered pembrolizumab as a standalone agent, though combination approaches may still be appropriate.
Before pembrolizumab can be considered, it is also important to test for EGFR mutations and ALK rearrangements - genetic changes that are treated with targeted therapies rather than immunotherapy. These tests should be part of any thorough initial assessment.
KEYNOTE-024: The landmark trial for high PD-L1 NSCLC
KEYNOTE-024 enrolled NSCLC patients with TPS 50% or higher and no EGFR or ALK mutations, comparing pembrolizumab to platinum-based chemotherapy as first-line treatment. The original results, published in 2016, showed significantly longer progression-free survival with pembrolizumab (10.3 months vs 6.0 months with chemotherapy).
The five-year update published in subsequent years showed approximately 31% of pembrolizumab patients were alive at five years, compared to 16% with chemotherapy. Median overall survival was 26.3 months with pembrolizumab versus 13.4 months with chemotherapy. These results established pembrolizumab monotherapy as the standard first-line treatment for PD-L1-high NSCLC.
KEYNOTE-189: Pembrolizumab plus chemotherapy
For patients with non-squamous NSCLC and lower or absent PD-L1 expression, KEYNOTE-189 evaluated the addition of pembrolizumab to standard chemotherapy. The trial demonstrated a significant benefit: median overall survival of 22 months in the pembrolizumab-plus-chemotherapy arm versus 10.7 months with chemotherapy alone. This combination is now standard practice for eligible patients who do not meet the criteria for monotherapy.
Home administration for NSCLC patients
NSCLC treatment can involve multiple cycles over an extended period - months or years for responding patients. The subcutaneous pembrolizumab formulation, administered at home by a qualified nurse, removes the need for repeated oncology day-unit visits. For patients managing fatigue and other treatment effects, eliminating regular hospital travel can have a meaningful impact on daily life and quality of care.
Eligibility for home administration follows the same criteria as the IV route, with additional assessment of suitability for home treatment. Not every NSCLC patient will be appropriate, but for many it represents a genuinely better way to receive an effective treatment.
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