Christine Megerdichian Parseghian, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, talks on the most exciting updates in colorectal cancer presented at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting. Within the anti-EGFR rechallenge space, the Phase III PARADIGM trial (NCT02394795) demonstrated promising results when comparing the anti-EGFR, panitumumab, versus the anti-VEGFR, bevacizumab, in combination with mFOLFOX6, whereby a significant increase in overall-survival (OS) was observed in patients receiving anti-EGFR. Patients involved in this trial had progressed on previous treatment options and as such, the findings introduces a new treatment option for patients in the third-line setting. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.
Christine Megerdichian Parseghian, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses overcoming acquired resistance to anti-EGFR therapies. A study was conducted on acquired resistance mutations occurring within the first- or third-line setting via the investigation of plasma samples from three large Phase III trials. Patients being treated in the third-line setting had significantly higher rates of acquired resistance mutations than those treated in the first-line. Additionally, patients who were being treated with chemotherapy plus anti-EGFR had significantly lower rates of acquired mutations compared to patients treated with anti-EGFR monotherapy. These findings raise implications on how best to overcome both acquired genomic and transcriptomic resistance to anti-EGFR therapies. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.
In this discussion, leading experts Yi Lin, MD, PhD, Mayo Clinic, Rochester, MN, Krina Patel, MD, MSc, The University of Texas MD Anderson Cancer Center, Houston, TX, Suzanne Trudel, MD, MSc, Princess Margaret Cancer Centre, Toronto, Canada, and Frederick Locke, MD, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, share their highlights from the lymphoma and myeloma sessions that took place at the 4th International Workshop on CAR-T (iwCAR-T) 2022 held in Tampa, FL. The experts share their excitement for the practice-changing trial data demonstrating the benefit of CAR-T therapy in second line in large B-cell lymphoma (LBCL), as well as for the possibility of approaching a cure in follicular lymphoma (FL). They then move on to discuss strategies to overcome the challenges associated with CAR-T therapy in multiple myeloma, including allogeneic CAR-Ts, where they discuss emerging data on various allogeneic CAR-T products. The experts then comment on the potential of bispecific antibodies in myeloma and how patients might be selected to receive BCMA-directed CAR-T therapy or bispecific antibodies in the future. Finally, the experts discuss real-world data on CAR-T therapy for mantle cell lymphoma (MCL) and multiple myeloma.
In this discussion chaired by David Maloney, MD, PhD, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA, Caron Jacobson, MD, MMSc, Dana Farber Cancer Institute, Boston, MA, and Loretta Nastoupil, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, talk on moving CAR-T therapy earlier in the treatment algorithm of high-risk large B-cell lymphoma (LCBL), and share their thoughts on the follow-up data of studies evaluating CAR-T therapy in mantle cell lymphoma (MCL) and follicular lymphoma (FL). Based on the results of the TRANSFORM (NCT03575351) and ZUMA-7 (NCT03391466) studies, the experts debate which LBCL patients should be selected to receive CAR-T therapy or autologous transplantation in the second-line setting. Additionally, Dr Maloney, Dr Jacobson and Dr Nastoupil comment on encouraging data from the ZUMA-12 study (NCT03761056) which provides strong evidence for further testing CAR-T therapy in the frontline setting. Moving forward, the experts talk on the efficacy of brexucabtagene autoleucel (brexu-cel) in MCL, and also talk on the updated data from the ZUMA-5 study (NCT03105336) in patients with FL, discussing the possibility of administering this therapy in the outpatient setting and of approaching a cure. This interview took place at the 4th International Workshop on CAR-T (iwCAR-T) 2022 held in Tampa, FL.
Arvind Dasari, MD, MS, The University of Texas MD Anderson Cancer Center, Houston, TX, talks on the use of circulating tumor DNA (ctDNA) to guide patient care. The use of ctDNA in cancer care ranges from early diagnosis to cancer screening. Dr Dasari explains how through observing changes in ctDNA levels across time during treatment for patients, ctDNA can aid in treatment decision making. However, this remains a challenge due to a current lack in the cut-offs for which level of ctDNA is considered a response versus progression. There are several ongoing clinical trials investigating the use of ctDNA for the early detection of cancers that are otherwise difficult to diagnose, such as biliary tract cancer (BTC) and pancreatic cancer (PC), that do not have current methods of screening and additionally for cancers such as breast and lung cancer where the screening methods used in clinical practice are faced with challenges, including cost, uptake and reliability. Furthermore, ctDNA can be utilized to detect minimal residual disease (MRD) in patients who have undergone surgery or other curative methods of treatment. Dr. Dasari explains that the detection of MRD is a highly powerful prognostic factor. Patients who are positive for MRD following curative treatment have a very high risk of recurrence and those who are negative for MRD have a substantially lower risk. The question is for patients who are MRD-negative, who per current guidelines would be receiving adjuvant chemotherapy, whether the intensity of therapy could be safely deescalated, reducing the associated unpleasant side effects. In the metastatic setting, ctDNA can be used for tumor profiling with fast results. Moreover, ctDNA can monitor resistance mechanisms in terms of targeted therapy, such as anti-EGFR in colorectal cancer (CRC), to then discern whether the resistance mechanism can be targeted with other targeted treatments and observe via the ctDNA if the cancer gets cleared from the mechanism of resistance to be able to subsequently rechallenge the tumor with anti-EGFR once again. Ongoing studies are attempting to establish the clinical utility of ctDNA to guide patient care, to ultimately improve patient outcomes. This interview took place at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2022.
Scott Kopetz, MD, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX, outlines the impact circulating tumor cells (CTCs) are making for gastrointestinal cancers empowered by the significant improvement in next-generation sequencing (NGS) methodologies. NGS allows for the detection of microscopic amounts of tumor DNA found in patients. Many NGS approaches sequence the primary tumor and search for specific alterations present in the plasma of patients to determine whether any disease remains following treatment. Such techniques allow for high positive predictive value and as such if CTCs are discovered in a patient there is a high probability that the cancer persists. Early studies are focusing on whether the delivery of adjuvant therapy can be improved using CTC detection. For some patients following surgery, microscopic amounts of disease may be left behind which a CT scan may be unable to detect. However, such microscopic amounts of disease may be found via the detection of circulating tumor DNA. On the other hand, there is the issue of overtreating patients. Many patients with stage III colon cancer can be treated with surgery alone, sparing the toxicities associated with chemotherapy. CTC detection can help uncover which patients require chemotherapy. Dr. Kopetz explains how the detection of the cancer before it appears radiographically in patients who had undergone adjuvant chemotherapy and surgery is the area in which CTCs are generating the most impact. Using CTCs the cancer may be detected before it reaches a point in progression where it can be seen radiographically. This interview took place at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.
Eric K. Singhi, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, gives an overview of recent drug approvals for non-small cell lung cancer (NSCLC). In the past few years, there has been significant progress in the development of drugs for both early-stage and advanced NSCLC. In particular, adjuvant therapy with atezolizumab and osimertinib and novel targeted therapies have considerably improved patient outcomes. This interview took place during the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, D.C.
Eric K. Singhi, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, emphasizes the importance of improving the experience of patients with metastatic non-small cell lung cancer (NSCLC). For instance, by identifying toxicities earlier in the treatment course and having clinically meaningful interventions. This interview took place during the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, D.C.
Nathan Fowler, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, shares an overview of the phase III RELEVANCE trial (NCT01650701) of rituximab and lenalidomide (R2) versus rituximab-chemotherapy followed by rituximab maintenance in patients with high tumor burden, untreated follicular lymphoma (FL). Six years after initial treatment, both treatment arms demonstrated similar efficacy and survival, highlighting R2 as a viable chemotherapy-free treatment option. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Nathan Fowler, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, provides an update on the Phase II ELARA trial (NCT03568461), which assessed tisagenlecleucel (tisa-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with follicular lymphoma (FL). Tisa-cel improved progression-free survival across different subtypes of FL, including patients who progressed within 2 years (POD24). Patients who received tisa-cel in an outpatient setting also were less likely to require hospitalization, highlighting the ability for CAR T-cell therapies to be administered in an outpatient setting for patients with a low-risk disease. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Curtis Lachowiez, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, outlines the tools and platforms used for the diagnosis of acute myeloid leukemia (AML). Morphological assessment of the bone marrow is the main diagnostic strategy used to identify the type of leukemia a patient has. As technology has advanced, several additional tools are used to provide more detail on a patient’s disease. Cytogenetic and molecular genetic analyses are conducted using fluorescence in situ hybridization (FISH), next-generation sequencing, and flow cytometry. Dr Lachowiez explains the extra information that can be provide by the identification of prognostic and predictive genetic changes using these techniques. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.