Articles related to CHECKPOINT INHIBITORS

The phase 3 KEYNOTE-048 trial compares pembrolizumab with or without concurrent chemotherapy to cetuximab-chemotherapy in patients with recurrent or metastatic head and neck SCC. Patients were evaluated in subgroups based on PD-L1 expression. In median survival, pembrolizumab + chemotherapy outperformed cetuximab + chemotherapy in all patient subgroups regardless of PD-L1 expression. In the PD-L1 CPS 1-19 subgroup, pembrolizumab alone slightly outperformed cetuximab + chemotherapy. In the PD-L1 CPS < 1 subgroup median survival was significantly lower with pembrolizumab alone.

Sixty patients with EGFR-amplified gastroesophageal adenocarcinoma(GEA) received EGFRi, including 31 of 60 patients (52%) with concurrent chemotherapy. Across treatment lines, patients achieved a 43% objective response rate with a median PFS of 4.6 months. Typical OS with first-line initiation of non-EGFRi therapy in patients with EGFR-amplified GEA is 11.2 months, as determined by analysis of a deidentified clinicogenomic database. Despite this benefit, analysis of that database for January 2011 through December 2020 suggests that only 5% of patients with EGFR-amplified GEA received EGFRi.

Both immune checkpoint inhibitors (ICIs) and VEGF receptor inhibitors are approved for advanced renal cell carcinoma (RCC) treatment and can cause cardiovascular events (CVs). This randomized study of avelumab plus axitinib vs. sunitinib used prospective monitoring of LVEF and serum cardiac biomarkers to assess for the development of major adverse CV events. The results indicate patients with high baseline troponin T levels and who receive combination ICI and VEGF receptor inhibitor therapy should be monitored closely for adverse cardiac events.

In a randomized clinical trial of 128 patients with refractory mCRC, the addition of the PD-L1 inhibitor atezolizumab to capecitabine and bevacizumab therapy resulted in marginally longer PFS vs the placebo comparator arm. However, the median improvement — 4.4 vs 3.6 months – was deemed not clinically relevant.

PIK3CA is the most mutated oncogene across many of the common solid tumor types. Consequently, targeting PIK3CA has been of major clinical interest. Initial efforts at have not been promising, however. The limiting factors have primarily been lack of isoform specificity of inhibitors and dose-limiting toxicities. This study evaluates copanlisib, an α and δ isoform–specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with PIK3CA mutations.

In this cohort study of 34,131 patients with cancer published in JAMA Oncology, trial ineligibility was associated with a greater likelihood of immune checkpoint inhibitor (ICI) monotherapy use compared with non-ICI therapy. Among trial-ineligible patients, there were no overall survival differences between treatment with ICI monotherapy, ICI combination therapy, and non-ICI therapy.