Pembrolizumab works better than chemotherapy alone as initial treatment

<p class="article-intro">People with advanced non-small-cell lung cancer (NSCLC) with a PD-L1 expression of 1 % or more who were first treated with pembrolizumab lived a median of 4 8 months longer than those who received chemotherapy. In addition, severe side effects occurred in fewer patients receiving pembrolizumab than chemotherapy (18 % vs. 41 % ).</p> <hr /> <p class="article-content"><p>According to the authors, this study (KEYNOTE-042) is the largest clinical trial of pembrolizumab as a standalone therapy. 1274 people with locally advanced or metastatic NSCLC were randomly assigned to receive chemotherapy (paclitaxel plus carboplatin or pemetrexed plus carboplatin) or pembrolizumab. Both squamous and non-squamous cancers were included, but not cancers with genetic changes that can be treated with targeted therapies (EGFR and ALK inhibitors). <br />For the analysis, researchers explored treatment benefits in three patient groups according to tumor PD-L1 expression score: at least 50 % (599 patients), at least 20 % (818 patients), and at least 1 % (1274 patients). Equal numbers of patients in each PD-L1 expression group received pembrolizumab and chemotherapy.</p> <p>The median follow-up time was 12,8 months. Compared to those receiving standard chemotherapy, patients who received pembrolizumab had a longer median overall survival, regardless of PD-L1 expression in the tumor. The benefit of pembrolizumab was greater when the level of PD-L1 expression was higher:</p> <ul> <li>PD-L1 50 % or more: 20 months with pembrolizumab vs. 12,2 months with chemotherapy</li> <li>PD-L1 20 % or more: 17,7 months with pembrolizumab vs. 13 months with chemotherapy</li> <li>PD-L1 1 % or more: 16,7 months with pembrolizumab vs. 12,1 months with chemotherapy</li> </ul> <p>More research is needed to define patient groups who benefit from pembrolizumab. The three broad groupings by PD-L1 expression in the current analysis do not allow researchers to predict the benefit from pembrolizumab for patients with a specific PD-L1 expression level. <br />Additionally, it is not yet clear whether pembrolizumab combined with chemotherapy is better than pembrolizumab alone in patients who express PD-L1, as there have not been head-to-head comparison trials of the two approaches.<br /> Ongoing research is also exploring use of adjuvant pembrolizumab and combinations of immunotherapy with bevacizumab-containing combination regimens as part of initial therapy for NSCLC.</p> <p>Based on findings from a previous, smaller clinical trial (KEYNOTE-024), the FDA approved pembrolizumab for initial treatment of NSCLC with high PD-L1 expression (score of at least 50 % ), which account for about one-third of these cancers.</p> <p><strong>Reference:</strong> <br />Lopes G et al.: Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) &ge;1 % : Open-label, phase 3 KEYNOTE-042 study. ASCO Annual Meeting 2018, abstract #LBA4</p></p>