2023 ASCO Annual Meeting: Breakthroughs in Cancer Care and Advances in CAR T-cell Therapy

The 2023 ASCO Annual Meeting not only featured numerous presentations on research related to solid tumors, but also highlighted recent developments in CAR T-cell therapy targeting various blood cancers. In addition, the National Institutes of Health (NIH) has funded a number of long-term studies to examine issues such as reducing racial disparities in cancer care and strategies to increase recruitment of underrepresented populations in clinical trials, the results of which were also presented at this year’s meeting.

Related article: 2023 ASCO Annual Meeting: Progress in Solid Tumor Treatment Research, and Promising Results in Emerging Therapies 

CAR T-Cell Therapy Offers New Hope to Hard-to-treat Blood Cancer Patients

At the 2023 ASCO Annual Meeting, researchers presented studies that demonstrated the potential of chimeric antigen receptor (CAR) T-cell therapy to revolutionize cancer care. Two notable examples included the Phase 3 ZUMA-7 trial on axicabtagene ciloleucel (axi-cel) as a second-line treatment for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), as well as the Phase 3 CARTITUDE-4 trial on ciltacabtagene autoleucel (cilta-cel) for treating multiple myeloma (MM).

Axi-cel, sold under the brand name Yescarta, is the blockbuster drug developed by Kite Pharma and it won FDA nod in April 2022 as the first CAR T-cell immunotherapy approved for adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). This year, Kite presented the primary overall survival analysis of the Phase 3 randomized ZUMA-7 study of axi-cel versus standard-of-care (SOC) therapy in R/R LBCL. Results showed that when compared with the SOC chemotherapy and stem cell transplant, using axi-cel as a second-line treatment demonstrated a significant improvement in overall survival (OS, 54.6% vs 46.0%) and progression-free survival (PFS, 41.8% vs 24.4%) over a period of 48 months. In addition, the safety profile of axi-cel remained consistent with prior studies.

Under the brand name Carvykti, cilta-cel is Janssen’s first cell therapy for treating patients with relapsed and refractory MM and it received FDA approval in late February. As per Janssen’s presentation, cilta-cel was superior over the SOC combination therapy as it significantly prolonged 12-month PFS (76% vs 49%) in patients with relapsed MM who had received 1 to 3 lines of prior treatment. More importantly, this CAR T-cell therapy reduced the risk of disease progression or death by 74% when compared to using SOC treatment regimens, highlighting the potential for cilta-cel to become a key therapy for MM patients in an earlier-line treatment, probably after the first relapse.

Closing the Racial Gap in GI Cancer Treatment Through Medicaid Expansion

Across the United States, racial minorities experience disparities in receipt of cancer treatment and survival. Take gastrointestinal (GI) cancers as examples, previous studies have indicated that Black patients appear to be under-treated compared to White patients for GI cancers, being less likely to receive standard of care treatments, surgeries and adjuvant therapies. The disproportionately low operative rates contribute to the known survival disparity between Black and White patients. 

Through the optional Medicaid expansion provision of the Affordable Care Act, states received federal funding to expand Medicaid eligibility criteria in order to improve healthcare access for disadvantaged populations. At the 2023 ASCO Annual Meeting, researchers from University of Texas MD Anderson Cancer Center and Albany Medical College presented an NIH-sponsored study aimed to investigate the effect of Medicaid expansion on racial disparities in mortality among patients with GI cancers, including pancreatic cancer, colorectal cancer and gastric adenocarcinoma of any stage. 

Based on data from the National Cancer Database (2009-2019) involving approximately 86,000 GI cancer patients, the cross-sectional cohort study compared the adjusted 2-year mortality separately among Black and White patients residing in Medicaid expansion states (MES) and non-expansion states (non-MES) before (2009-2013) and after (2014-2019) expansion. Results showed a link between Medicaid expansion and an increase in receipt of chemotherapy as well as a greater reduction in 2-year mortality rates for Black patients residing in MES than for those in non-MES. Existing racial disparities in mortality remained the same or worsened in non-MES but in almost all cases were mitigated in MES following Medicaid expansion.

“Our study provides compelling data that show Medicaid expansion was associated with improvement in survival for both Black and White patients with gastrointestinal cancers. Additionally, it suggests that Medicaid Expansion is one potential avenue to mitigate existing racial survival disparities among these patients,” said Dr. Naveen Manisundaram from MD Anderson Cancer Center, one of the main authors of the study.

Strategies to Increase Accrual of Underrepresented Populations in Clinical Trials

In spite of the unprecedented fast pace of the development of new approaches of disease prevention, diagnosis and treatment, there are still numerous underrepresented populations (URPs), encompassing racial and ethnic minorities, women, rural populations, and younger and older populations in the U.S., are less able to benefit from these discoveries because they are not adequately represented in clinical research studies. Such inequalities in clinical trial participation not only compromise generalizability of clinical research findings to the whole population, but also possibly result in failure of clinical trials and limited access to effective medical interventions, worsening health disparities among URPs. In particular, there has been historically low enrollment of URPs in clinical trials, thereby impeding progress in cancer treatment, symptom intervention, and prevention. 

Also sponsored by NIH, the Alliance for Clinical Trials in Oncology (Alliance), as a part of the National Clinical Trials Network (NCTN) and NCI Community Oncology Research Program (NCORP) under the umbrella of the National Cancer Institute (NCI), launched a multi-pronged strategy in 2018 to increase enrollment of underrepresented minorities (URMs) in NCTN cancer treatment and control trials. Examples of intentional approaches adopted included funding junior investigators and special projects focusing on URPs, translation services of materials for patients from URMs, opening studies at NCORP Minority Underserved Sites, closing protocol enrollment to majority populations; and increasing the study sample size to enroll additional minority participants to allow for analyzing intervention effects by subgroups. 

According to lead study author Prof. Electra D. Paskett from the Ohio State University, the above-mentioned approaches successfully increased the accrual of URMs to Alliance trials, reporting an increased accrual from 13.6% to 25.3% for treatment and 13% to 21.5% for cancer control trials during 2018-2023. “This reflects an overall increase from 13.5 % to 23.6% of URMs for all trials, a 74.8% improvement. With more diversity in clinical trials, we can make the results of trials representative of (and applicable to) all patients,” said Prof. Paskett. 

Author

Richard Chau