Diagnosis for NSCLC
- The analysis of PD-L1 expression by an immunohistochemistry (IHC)-based test to determine PD-L1 expression levels is recommended for all patients with newly diagnosed advanced NSCLC.
- Prior to initiation of immunotherapy, tests recommended by the majority of the Task Force included computerized tomography (CT) of the chest, abdomen, and pelvis and thyroid function tests (in addition to routine lab tests).
- PD-L1 testing is recommended in newly diagnosed patients with metastatic disease, including those tested for EGFR/ALK/ROS1 mutations whose results are awaited. (A)
Table 1. PD-L1 Assay Characteristics and Performance in NSCLC
| Assay | Antibody | FDA-approved Indication in NSCLC | Cutoff Value | Performance |
|---|---|---|---|---|
| 22C3 IHC pharmDx | Monoclonal mouse anti-PD-L1, Clone 223 | Approved as a companion diagnostic to select patients with advanced NSCLC for treatment with pembrolizumab first-line (TPS ≥50%) or after progression on a platinum containing chemotherapy regimen (TPS ≥1%) |
| Found to be closely aligned with 28–8 and SP263 IHC assays |
| 28–8 IHC pharmDx | Monoclonal Rabbit anti-PD-L1, Clone 28–8 | Approved as a complementary diagnostic to aid in non-squamous NSCLC patient selection for treatment with nivolumab | Qualitative test reported as a percentage of tumor cells exhibiting positive membrane staining | Found to be closely aligned with 22C3 and SP263 IHC assays |
| PD-L1 (SP142) Assay | Monoclonal Rabbit anti-PD-L1, Clone SP142 | Approved as a complementary diagnostic to aid in NSCLC patient selection for treatment with atezolizumab | PD-L1 expression in ≥50% tumor cells or ≥10% immune-infiltrating cells is associated with enhanced survival | Consistently stained fewer PD-L1 tumor cells |
| PD-L1 (SP263) Assay | Monoclonal Rabbit anti-PD-L1, Clone SP263 | CE mark only, not approved by the FDA for patients with NSCLC | The CE mark was granted and expanded based on demonstrated equivalency to the 28-8 and the 22C3 IHC assays | Found to be closely aligned with 22C3 and 28-8 IHC assays |
Treatment for NSCLC
Figure 1. Advanced/Metastatic NSCLC Treatment Algorithm
- PD-L1 testing for all newly diagnosed patients is recommended.
- First line pembrolizumab monotherapy should be used for patients with squamous cell NSCLC and PD-L1 TPS ≥50%. (A)
- FDA approval is anticipated for first line treatment with pembrolizumab in combination with carboplatin & (nab-) paclitaxel for patients with advanced, squamous cell NSCLC.
- For patients with squamous histology and PD-L1 TPS <50%, combination pembrolizumab + chemotherapy (carboplatin or (nab-)paclitaxel) can be used pending FDA approval.
- For patients with non-squamous, advanced NSCLC and an actionable mutation (EGFR, ALK, or ROS1+), targeted therapies should be used over pembrolizumab or pembrolizumab + chemotherapy. (A)
- Atezolizumab, nivolumab, or pembrolizumab (TPS ≥1%) should be used as third-line therapy in all patients with actionable mutations after disease progression with targeted agents followed by platinum-containing chemotherapy. (A)
- These therapies can also be used second-line in patients with squamous histology and PD-L1 TPS <50% who were not previously treated with a checkpoint inhibitor.
- For patients with non-squamous, advanced NSCLC with PD-L1 TPS <50% and no actionable mutations, patients should receive first-line pembrolizumab + pemetrexed and carboplatin. (A)
- Pembrolizumab is recommended first-line in patients with PD-L1-positive (TPS ≥50%) non-squamous metastatic NSCLC. (A)
- First line pembrolizumab + pemetrexed & carboplatin is also a treatment option.
- Durvalumab should be used in stage III patients who have not progressed post-chemoradiation. (A)
Definition of Evidence Grades
| Level | Definition |
|---|---|
| A | Strong supporting evidence-based data from prospective, randomized, controlled trials, meta-analyses, long-term follow-up of prospective, uncontrolled trials |
| B | Moderate supporting data from uncontrolled, prospective clinical trials |
| C | Weak supporting data from retrospective reviews and case reports |
| Percentages | Proportion of Task Force members favoring recommendation |
