KEYNOTE-062: Front-line Pembrolizumab is an alternative to chemotherapy for Gastric Cancers

<p class="article-intro">The KEYNOTE-062 phase III randomized clinical trial achieved its primary endpoint, showing that for patients with PD-L1-positive, HER2-negative, advanced gastric or gastroesophageal junction (G/GEJ) cancer, initial therapy with pembrolizumab resulted in comparable (non-inferior) overall survival as standard chemotherapy. </p> <hr /> <p class="article-content"><p>In this phase III trial Pembrolizumab with or without chemotherapy versus chemotherapy was disigned for patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Pembrolizumab was comparable to standard chemotherapy in select patients with advanced gastric or gastroesophageal junction adenocarcinoma. 39 % of patients with HER2-negative, advanced gastric or gastroesophageal junction adenocarcinoma with PD-L1 combined positive scores of 10 or more who received front-line pembrolizumab were alive after 2 years compared with 22 % of those who received systemic chemotherapy.<br /> Additionally, pembrolizumab showed clinically meaningful improvement in overall survival among patients with tumors that had high levels of PD-L1 expression. At two years, 39 % of patients (all of whom had high PD-L1 levels) that received pembrolizumab alone were alive, compared with 22 % of people who received standard chemotherapy. The trial also evaluated combined treatment with pembrolizumab and standard chemotherapy but found this regimen did not improve survival relative to chemotherapy alone.<br /> &ldquo;This trial shows that front-line pembrolizumab is effective and could provide a new opportunity for people newly diagnosed with advanced gastric or gastroesophageal junction cancers,&rdquo; said lead study author Josep Tabernero, MD, PhD, Head of the Medical Oncology Department at the Vall d&rsquo;Hebron Barcelona Hospital University Hospital and Institute of Oncology, Barcelona, Spain. &ldquo;There remains a significant unmet need for treatments for these cancers and our results reinforce the importance of continued research in this field.&rdquo;</p> <p><strong>About the Study</strong><br /> The trial enrolled 763 patients with a median age of 62 and 26 % had previous gastric surgery to remove a tumor. In total, 69 % had gastric cancer and 30 % had GEJ cancer, which are typically very similar types of tumors despite their adjacent locations according to Dr. Tabernero. Investigators focused only on HER2-negative cancers, which studies have shown have a higher chance of recurrence after treatment, to limit factors that could affect outcomes. PD-L1 expression was assessed via CPS. Previous studies of gastric or GEJ cancers have demonstrated that patients with a PD-L1 CPS of one or more may benefit from pembrolizumab, while a PD-L1 CPS of 10 or more indicates a higher likelihood of benefit. In the current trial, all patients had a PD-L1 CPS of one or greater, and 281 (37 % of the enrollees) had a score of 10 or more. The investigators randomly assigned patients, in equal numbers, to receive one of three treatment options as initial therapy: intravenous pembrolizumab, pembrolizumab and chemotherapy, or chemotherapy plus placebo. The patients were followed for a median of 11.3 months.</p> <p><strong>Key Findings</strong><br /> <em>Treatment with Pembrolizumab Alone:</em> The trial reached its primary endpoint, demonstrating that overall survival for pembrolizumab was non-inferior (comparable) to standard chemotherapy. A favorable survival outcome was seen among enrolled patients with PD-L1 CPS of 10 or more. Specific findings include:</p> <ul> <li>Patients with PD-L1 CPS 10 or more: Survival was superior for chemotherapy [hazard ratio = 0.69] -- median overall survival was 17.4 months for those receiving pembrolizumab compared with 10.8 months for those receiving chemotherapy. After 2 years, 39 % of people taking pembrolizumab were alive compared with 22 % of those taking chemotherapy.</li> </ul> <p><em>Treatment with Pembrolizumab and Chemotherapy:</em> Overall survival and progression-free survival (time until disease progression), regardless of CPS score, for the combination treatment of pembrolizumab and chemotherapy was comparable to that of chemotherapy alone.</p> <p><strong>Safety:</strong><br />The rates of serious side effects were lowest among patients treated with pembrolizumab alone. Grade 3 or higher toxic treatment-related adverse events were found in 17 % of people receiving pembrolizumab, 73 % of people receiving pembrolizumab and chemotherapy, and 69 % receiving only chemotherapy. The most common adverse events were nausea and fatigue. The safety profile of pembrolizumab was consistent with prior experiences of patients whohave been treated with it.</p> <p><strong>Next Steps</strong><br /> The investigators are currently analyzing subsets of the data to determine who benefitted the most. Dr. Tabernero noted that better biomarkers than PD-L1 are needed to truly determine who the best responders might be to pembrolizumab alone, as well as in combination with chemotherapy.</p></p> <p class="article-footer"> <a class="literatur" data-toggle="collapse" href="#collapseLiteratur" aria-expanded="false" aria-controls="collapseLiteratur" >Literatur</a> <div class="collapse" id="collapseLiteratur"> <p>Tabernero J et al: Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. ASCO Annual Meeting 2019, LBA4007</p> <p><br /><a href="https://at.universimed.com/fachthemen/1000001332">zur&uuml;ck zum ASCO 2019 Newsroom</a></p> </div> </p>