From the Guidelines
The treatment for pulmonary adenocarcinoma with PD-L1 expression of 1% should involve a combination of platinum-based doublet chemotherapy and immunotherapy, as it has been shown to improve survival compared to chemotherapy alone. For this low PD-L1 expression level, a common regimen includes carboplatin or cisplatin with pemetrexed, plus pembrolizumab (Keytruda) for non-squamous non-small cell lung cancer, as supported by the 5-year update of the phase III KEYNOTE-189 trial 1. The typical dosing is carboplatin AUC 5 or cisplatin 75 mg/m² with pemetrexed 500 mg/m² every 3 weeks, along with pembrolizumab 200 mg every 3 weeks.
Some key points to consider in the management of these patients include:
- Testing for actionable mutations (EGFR, ALK, ROS1, BRAF, NTRK, MET, RET) before starting treatment, as targeted therapies would be preferred if mutations are present 1
- Regular monitoring with imaging every 6-9 weeks during treatment, along with blood work to assess organ function
- Proactive management of side effects, including fatigue, nausea, immune-related adverse events (thyroid dysfunction, pneumonitis, colitis), and myelosuppression
The combination approach is recommended because low PD-L1 expression (1%) indicates limited benefit from immunotherapy alone, while the chemotherapy-immunotherapy combination has shown improved survival compared to chemotherapy alone in clinical trials, such as the CheckMate 9LA trial, which demonstrated an improvement in OS and PFS for all histology types and for all levels of PD-L1 tumor expression, including in the subset of patients with PD-L1 TPS 1%-49% 1.
From the Research
Treatment Options for Pulmonary Adenocarcinoma with PD-L1 Expression of 1%
- The treatment for pulmonary adenocarcinoma with PD-L1 expression of 1% is not explicitly stated in the provided studies, as they primarily focus on the correlation between PD-L1 expression and clinical outcomes, prognosis, and driver oncogene alterations.
- However, studies such as 2 and 3 suggest that PD-L1 expression can be used as a prognostic indicator for relapse-free survival (RFS) and overall survival (OS) in patients with lung adenocarcinoma.
- Additionally, 4 found that patients with high PD-L1 expression on tumor-associated macrophages (TAMs) or tumor cells had improved survival with adjuvant chemotherapy (ACT), which may be a potential treatment option for patients with pulmonary adenocarcinoma and low PD-L1 expression.
PD-L1 Expression and Clinicopathological Features
- Studies such as 3 and 5 have investigated the associations between PD-L1 expression and clinicopathological features, including driver oncogene alterations, in patients with lung adenocarcinoma.
- These studies found that PD-L1 positivity was associated with poor overall survival and poor relapse-free survival, although this was not statistically significant after adjusting for prognostic factors in the multivariate analysis.
- Furthermore, 6 found that PD-1 and PD-L1 expression was associated with favorable overall survival in patients with completely resected adenocarcinoma of the lung.
Potential Treatment Strategies
- Based on the provided studies, potential treatment strategies for pulmonary adenocarcinoma with PD-L1 expression of 1% may include:
- Adjuvant chemotherapy (ACT) 4
- Immunotherapy targeting the PD-L1 pathway 2, 4
- Tyrosine kinase inhibitors (TKIs) for patients with EGFR mutations or ALK rearrangements 5
- However, it is essential to note that these studies do not provide direct evidence for the treatment of pulmonary adenocarcinoma with PD-L1 expression of 1%, and further research is needed to determine the most effective treatment strategies for this specific patient population.