But, in those with 1% to 49% expression, there was no significant benefit for pembrolizumab versus chemotherapy,” Dr. “In the subset of patients with ≥50% expression, such as those in KEYNOTE-024, there was benefit for pembrolizumab. This option represents an addition to the NCCN Guidelines.Īt this time, single-agent pembrolizumab is not currently recommended in the NCCN Guidelines as frontline treatment for patients with NSCLC and PD-L1 expression <50%, although it is FDA approved in this setting based on data from the phase III KEYNOTE-042 trial. ![]() “I worry that some patients may not get to the second line if I don’t get chemotherapy in upfront,” he said, with admittedly cross-trial comparisons suggesting a higher response rate with the combination in those with PD-L1 expression ≥50%. 4 Although this regimen carries greater toxicity than pembrolizumab alone, clinicians and patients may consider it important to take their best shot early. ![]() 3 This finding showed PD-L1 expression ≥50% to be a critical cut point in selecting candidates for pembrolizumab and elevated single-agent pembrolizumab, for both adenocarcinoma and squamous cell carcinoma (SCC), as the panel’s preferred first-line option (category 1) when PD-L1 expression is ≥50%.Ĭhemotherapy + pembrolizumab (or atezolizumab + bevacizumab) is also a category 1 recommendation suitable for select patients with high PD-L1 expression (ie, those with a high disease or symptom burden), with KEYNOTE-189 showing improved OS compared with chemotherapy alone. In KEYNOTE-024, pembrolizumab more than doubled median overall survival (mOS) compared with chemotherapy for patients with PD-L1 expression ≥50%, improving mOS to 30.0 from 14.2 months with chemotherapy (hazard ratio, 0.63 P=.002). Gubens reminded listeners, because even with high PD-L1 expression these patients tend to have much poorer outcomes with single-agent immunotherapy. Use of first-line immunotherapy is restricted to patients without EGFR or ALK mutations, Dr. Two pivotal studies that evaluated first-line single-agent PD-1 inhibitors, both originally presented at the 2016 ESMO Congress, helped establish the PD-L1 cut point for use of single-agent immunotherapy in the first line: KEYNOTE-024 evaluated pembrolizumab in patients with PD-L1 expression ≥50%, producing positive results, 1 and CheckMate 026 evaluated nivolumab in patients with ≥5% PD-L1 expression, with negative results. ![]() Although not an optimal biomarker, PD-L1 expression is currently the best one for assessing whether patients are candidates for PD-1/PD-L1 inhibitors alone versus in combination, the NCCN panel emphasized in the guidelines. “PD-L1 testing is important for determining the appropriateness of single-agent immunotherapy in the first line,” Dr. PD-L1 Testing for Treatment in the First Line Optimal management of the unique toxicities associated with immunotherapy, which can be more frequent with these combinations, is also critical for good outcomes. Tumor mutational burden is emerging as a biomarker for efficacy but is not yet ready to be used in patient selection. In patients with SCC, carboplatin + paclitaxel or nab-paclitaxel with pembrolizumab is a category 1 recommendation. Alternately, a 4-drug regimen of carboplatin/paclitaxel/bevacizumab/atezolizumab is reasonable, especially for patients ineligible for pemetrexed. For patients with non-SCC disease, pembrolizumab + carboplatin/pemetrexed is preferred. For tumors with PD-L1 expression <50%, it is important to distinguish between nonsquamous and squamous cell carcinoma (SCC). Patients who lack a driver mutation and have tumor PD-L1 expression ≥50% are recommended to receive single-agent pembrolizumab, although combining with carboplatin/pemetrexed is also a reasonable choice, especially if there is higher burden of disease. For the use of immunotherapy in metastatic non–small cell lung cancer (NSCLC), the NCCN Guidelines for NSCLC reflect the importance of assessing levels of PD-L1 expression to determine the best use of PD-1/PD-L1 inhibitors, whether alone or in combination with chemotherapy.
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