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Description: CT239/10
Title: IMpower010: Efficacy and safety outcomes of adjuvant atezolizumab in the Asian subgroup after surgical resection of stage IB-IIIA NSCLC
Background:
The Phase III IMpower010 study (NCT02486718) met the endpoint of disease-free survival (DFS) at IA (clinical cut-off date: January 21, 2021) and significantly improved atezolizumab (Atezo) compared to best supportive care (BSC) in patients with stage II-IIIA non-small cell lung cancer (NSCLC) (including PD-L1) who underwent complete resection surgery and up to 4 cycles of cisplatin-based chemotherapy TC ≥1%). Based on these findings, Azezo has been approved as an adjuvant therapy for patients with stage II-IIIA NSCLC with PD-L1 TC ≥1% after surgical resection and platinum-based chemotherapy in the United States, China, and other countries, and as an adjuvant therapy for patients with stage II-IIIA NSCLC with completely resected PD-L1 TC≥50% in countries such as the European Union.
In previous DFS IA exploratory analyses, the Asian subgroup of the IMpower010 study showed efficacy and safety results consistent with the global population (Kenmotsu et al., JSMO 2021). Here, updated data on the first OS IA in the Asian subgroup of the IMpower010 study are presented.
Research Methods:
Eligible patients with stage IB (≥4cm)-stage IIIA NSCLC (AJCC/UICC v7) who are fully resected receive up to 4 cycles (21 days each) of cisplatin-based chemotherapy followed by 1:1 randomization to receive either Atezo 1200mg q3w (16 cycles) or BSC. The first pre-specified OS IA was performed at the clinical cut-off date (April 18, 2022). If DFS in the intention-to-treat (ITT) population reaches statistical significance in the final DFS analysis, OS in the ITT population will be formally tested. Exploratory OS and the most recent safety results were evaluated in the Asian subgroup.
Findings:
The Asian ITT population includes 233 patients from Japan, Chinese mainland, Taiwan, South Korea, and Hong Kong. As of the data cut-off date (April 18, 2022), the Atezo unstratified OS HR was 0.73 (95% CI: 0.28-1.88) in the PD-L1 TC≥1% (SP263) phase II-IIIA population (n=129), showing a favorable trend.
The Asian safety evaluable population included 229 patients (Atezo, n=122; BSC, n=107). Adverse events (AEs) of any grade were reported by patients with safety evaluable at 95.1% (Atezo) and 72.0% (BSC), with grade 3/4 AEs occurring in 24.6% and 13.1%, respectively. One patient in the Atezo group developed a grade 5 treatment-related AE. AEs leading to discontinuation of Aezo occurred in 21.3% of patients.
Conclusions of the study
IMpower010 Asian subgroup OS IA showed that in the PD-L1 TC≥1% of the stage II-IIIA population, Ataxo had a better OS trend compared to BSC, which is the same trend observed in the global population, although OS data in both populations were not formally tested at the first OS IA. With extended follow-up, the safety results of the IMpower010 Asian subgroup of Atezo remained largely unchanged, consistent with the results of the IMpower010 study in the global population, which is also consistent with the known safety profile of Atezo.
Description Number: LB327/1
DNA methylation biomarkers for early bladder cancer detection and treatment monitoring
Background:
Bladder cancer (BC) ranks fifth in the U.S. in malignancy, with more than 83,000 new diagnoses in 2023. The lack of sensitive detection for early bladder cancer detection and non-invasive diagnostic tools for treatment monitoring is a major challenge.
This study evaluates the clinical potential of bladder cancer CARE™ testing in early BC detection and monitoring of treatment response in BC patients.
Research Methods:
Urine samples were prospectively collected from patients from the University of Southern California with a prior history of BC according to the protocol approved by the Institutional Review Board. The patient is currently receiving surveillance/antineoplastic therapy and has also undergone genitourinary manipulation.
The enrollment period was from February 2019 to September 2021. Samples were analyzed using the Bladder CARE™ Assay, a DNA methylation assay used to quantitatively detect bladder cancer and upper urinary tract urethral cancer (UTUC) from urine. The results were reported as the Bladder CARE Index (BCI) and samples were classified as 'positive' (BCI>5), 'low-positive' (2.5<bci<5) or 'negative' (bci<2.5). <="" span="">
Studies assessed the correlation between BCI values and categories and clinicopathologic outcomes.
Findings:
A total of 110 patients with a previous diagnosis of BC (median age: 74 years; 86% male) were included. Within 36 months after tumor resection, 24 patients (21.8%) experienced tumor recurrence. Bladder CARE™ detected all cases of recurrence, on average 7.35 months earlier than cystoscopy.
Of the 55 patients (50%) who received antitumor therapy (45 BCG, 4 MMC, 2 GEM, 1 9UT, 1 GEM/DOCE, 1 MMC/BCG and 1 BCG, MMC and GEM), 7 (12. 7%) relapsed (non-remission patients), 11 (20%) did not relapse within 18 months of surgery (remission), and 37 patients (67.3%) had 18-month postoperative data that could not be classified as remission or non-remission. Bladder CARE™ detected an increase in BCI in 85.7% of patients without remission (mean BCI: 86.1) before histologic positivity. In patients in remission, BCI stabilized in the negative/low positive range postoperatively (mean BCI: 2.5). In addition, 20 out of 110 patients obtained pre- and post-operative evaluation data. Bladder CARE™ testing showed that 19 of the 20 patients (95%) had a decrease in BCI after surgery.
Conclusions of the study
This prospective study highlights the ability of bladder CARE™ testing to detect BC months in advance compared to the "gold standard" test. In addition, its quantitative nature provides prognostic insights and enables non-invasive monitoring of patient response to anti-tumor therapy. Larger studies will be conducted in the future to validate these encouraging findings.
Description No.: LB349/23
Cysteine-restricting enhances anti-tumor immunity in colorectal cancer
Background:
Colon cancer is the second leading cause of cancer death worldwide, and there are still problems with multidrug resistance and serious adverse reactions. Previous studies have shown that sulfur-containing amino acids are involved in tumor development, drug resistance, and immune evasion.
Here, this study suggests that limiting the intake of sulfur-containing amino acids may be a novel strategy for the treatment of colorectal cancer.
Research Methods:
The researchers evaluated the effect of sulfur-containing amino acids (SARs) restriction on different cell subsets in the tumor microenvironment by performing single-cell sequencing of azomethane/dextran sodium sulfate (AOM/DSS)-induced colon carcinogenesis.
The researchers used custom-made SLC7A11-neutralizing antibodies to limit cysteine intake and examined its therapeutic significance and underlying molecular mechanisms by RNA-seq, multiplex immunofluorescence staining, and western blotting.
Findings:
In the AOM/DSS model, SAR resulted in a slight weight loss in mice compared to a normal diet. However, this dietary restriction significantly improved the survival rate of mice and effectively inhibited tumor growth.
Single-cell sequencing results showed that the proportion of T cells in the tumor microenvironment increased significantly under the action of SAR. This suggests that limiting the intake of sulfur-containing amino acids may be a promising anti-tumor strategy.
Previous studies have shown that cysteine transporters SLC7A11 highly expressed in a variety of tumors, including colorectal cancer. To further investigate the role of cysteine in colorectal cancer, the researchers developed a neutralizing antibody 1A4 against SLC7A11.
The results showed that 1A4 could significantly inhibit the development of colorectal cancer in mice. It is well known that 85% of microsatellite stable colorectal cancers have little benefit from treatment with immune checkpoint inhibitors. Compared with PD-1 monoclonal antibody and CTLA-4 monoclonal antibody, 1A4 can significantly inhibit the growth of CT26 in vivo. The results of multiplex immunofluorescence staining showed that 1A4 could significantly increase the proportion of CD8+ T cells in colorectal cancer tissues.
Conclusions of the study
Restricting cysteine intake can significantly inhibit the growth of colorectal cancer, increase the proportion of CD8+ T cells, and enhance anti-tumor immunity.
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