Radiation-Free Immunotherapy Approach Offers Hope for Locally Advanced Lung Cancer
A small study from Japan suggests pembrolizumab and chemotherapy alone may sustain strong survival outcomes in select PD-L1–high NSCLC patients
In patients with unresectable, locally advanced non–small cell lung cancer (NSCLC) showing high PD-L1 expression, a radiation-free combination of pembrolizumab (Keytruda) and platinum-based chemotherapy achieved a 67% two-year progression-free survival rate and 81% overall survival, with manageable toxicity.
Study Details
Researchers at the Kobe Minimally Invasive Cancer Center in Japan conducted the Evolution phase II trial to test whether radiation could be safely omitted for patients with unresectable, locally advanced NSCLC and PD-L1 tumor proportion score (TPS) of 50% or higher. The findings, published in Lancet Oncology, mark the first trial exploring pembrolizumab plus chemotherapy without radiotherapy for this patient group.
Currently, the standard of care for these patients is chemoradiotherapy followed by durvalumab (Imfinzi), based on the landmark PACIFIC trial. While effective, that regimen often carries substantial risk of radiation pneumonitis and esophageal injury, limiting tolerability especially in older or frailer patients.
Methodology
The single-arm study enrolled 21 adults (median age 73) with unresectable, locally advanced NSCLC. Sixteen had non-squamous disease and received pembrolizumab, a platinum-based agent, and pemetrexed. Five patients with squamous histology received pembrolizumab, carboplatin, and nab-paclitaxel (Abraxane).
Following four cycles of induction therapy, patients continued pembrolizumab-based maintenance for up to two years or until progression.
Key Findings
2-year progression-free survival: 67% (90% CI 46–83)
2-year overall survival: 81% (90% CI 44.4 to not reached)
Objective response rate: 81% (8 complete, 9 partial responses)
Median follow-up: 32.5 months
Toxicity: Grade ≥3 adverse events occurred in 13 patients (62%), most commonly neutropenia and pneumonia.
Notably, median PFS was not reached, and median OS reached 44.4 months. Researchers concluded that this approach might offer a potential alternative for patients with PD-L1–high NSCLC who are ineligible for radiation or wish to avoid its side effects.
Implications for Practice
If validated in larger randomized trials, this strategy could represent a less toxic pathway for select patients, improving quality of life while maintaining disease control. However, experts caution against premature adoption.
In an accompanying commentary, Drs. Ernest Nadal and Arturo Navarro-Martin of Spain noted that residual disease rates remain a concern, potentially affecting long-term cure prospects. They emphasized that “non-inferior efficacy must be proven before such radiation-free regimens can be integrated into clinical practice.”
For now, the study adds to growing interest in treatment de-escalation strategies balancing efficacy and toxicity in cancer care.