Articles related to CHECKPOINT INHIBITORS

The 2023 AACR meeting has seen a large number of clinical abstracts presented, demonstrating that science from the lab is moving to the clinic. Examples include an RNA vaccine from Moderna in combination with pembrolizumab in a neoadjuvant setting in patients with melanoma, and the AEGEAN trial, which looks at perioperative therapy in patients with lung cancer. The conference is also seeing a focus on more diverse speakers, including junior investigators. The field of mRNA cancer vaccines is evolving, with personalised vaccines being used to activate the immune system in combination with checkpoint inhibitors, resulting in positive results in some cancers. The conference is an opportunity to learn about new science, make new connections and collaborations, and gain a better understanding of how to push the field forward.

This CME program discusses how Bruton’s tyrosine kinase inhibitors (BTKi) have improved treatment for chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and other B-cell malignancies. However, due to adverse events and treatment resistance, many patients discontinue treatment. A new generation of BTKi with a different mechanism of action (MOA) is emerging as a possible alternative. The program presents four modules that discuss the MOAs of covalent and non-covalent BTKi, current practices for using BTKi in treatment of CLL and MCL, the efficacy and safety data for novel BTKi, and the potential role of non-covalent BTKi in future treatment plans.

Results from the RUBY trial of dostarlimab and the GY018/Keynote-068 of pembrolizumab were presented at the 2023 SGO Annual Meeting on Women’s Cancer in March and were simultaneously published in The New England Journal of Medicine. The studies examined the efficacy and safety of the medications in all individuals and those with mismatch repair deficient (dMMR) illness. Each trial examined a separate PD-1 inhibitor, pembrolizumab or dostarlimab, in combination with chemotherapy in patients with advanced or recurrent endometrial cancer. In individuals with dMMR illness, both medications lowered the chance of disease progression or death by roughly 70%.

The article discusses the expanding landscape of targeted therapies for patients with advanced metastatic non-small-cell lung cancer (NSCLC), with nine targetable oncogenes and seven approvals within the last five years. With these emerging therapeutic options, the article emphasizes the importance of understanding the existing data on immune checkpoint inhibitors (ICIs) for each oncogene-driven lung cancer to guide the selection and sequencing of therapeutic options. The article reviews the clinical data on ICIs for each of the driver oncogene-defined lung cancer subtypes, including efficacy, toxicities, and potential strategies to enhance ICI efficacy in oncogene-driven NSCLC.

Data on patients with mismatch repair deficiency (MMRD) CRC, the majority of whom could not undergo surgery due to various health conditions unrelated to cancer, were presented at the 2023 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI). Instead of radiation therapy or chemotherapy, the patients received immunotherapy with checkpoint inhibitors. It should be noted that the patients were treated outside of clinical trials. The overall response rate in this patient group was 74%, with 57% of those who responded experiencing complete tumor regression. Some of the patients have been in complete remission for a year or more after their diagnoses. The data indicate that immunotherapy is an effective treatment for patients who are unable to undergo surgery for a variety of reasons, including advanced age or a variety of health issues.

Charu Aggarwal, MD, MPH, of the University of Pennsylvania’s Abramson Cancer Center in Philadelphia, H. Jack West, MD, of the City of Hope Comprehensive Cancer Center in the Los Angeles area, and Devika Das, MD, of the University of Alabama at Birmingham discuss the distinction between uncommon EGFR mutations and sensitizing mutations, as well as the lack of data on how to treat these patients with tyrosine kinase inhibitors.