METHODS: DNA were extracted from formalin-fixed, paraffin-embedded tissues obtained from 33 CRC patients diagnosed between 2018 and 2019. Amplifications of codons 12 and 13 of KRAS were conducted using conventional polymerase chain reaction (PCR) followed by Sanger sequencing.
RESULTS: Mutations were identified in 36.4% (12/33) of patients, with G12D (50%) being the most frequent single-point mutation observed, followed by G12V (25%), G13D (16.7%), and G12S (8.3%). No correlation was found between mutant KRAS and location of the tumor, staging, and initial carcinoembryonic antigen (CEA) level.
CONCLUSION: Current analyses revealed that a significant proportion of CRC patients in the East Coast of Peninsular Malaysia have KRAS mutations, where this frequency is higher compared to those in the West Coast. The findings of this study would serve as a precursor for further research that explores KRAS mutational status and the profiling of other candidate genes among Malaysian CRC patients.
METHODS: This retrospective study examined data of patients with ALK-positive NSCLC from 18 major hospitals (public, private, or university teaching hospitals) throughout Malaysia between January 1, 2015 and December 31, 2020 from the National Cardiovascular and Thoracic Surgical Database (NCTSD). Data on baseline characteristics, treatments, radiological findings, and pathological findings were collected. Overall survival (OS) and time on treatment (TOT) were calculated using the Kaplan-Meier method.
RESULTS: There were 1581 NSCLC patients in the NCTSD. Based on ALK gene-rearrangement test results, only 65 patients (4.1%) had ALK-positive advanced NSCLC. Of these 65 patients, 59 received standard-of-care treatment and were included in the analysis. Crizotinib was the most commonly prescribed ALK inhibitor, followed by alectinib and ceritinib. Patients on ALK inhibitors had better median OS (62 months for first-generation inhibitors, not reached at time of analysis for second-generation inhibitors) compared to chemotherapy (27 months), but this was not statistically significant (P=0.835) due to sample-size limitations. Patients who received ALK inhibitors as first-line therapy had significantly longer TOT (median of 11 months for first-generation inhibitors, not reached for second-generation inhibitors at the time of analysis) compared to chemotherapy (median of 2 months; P<0.01).
CONCLUSION: Patients on ALK inhibitors had longer median OS and significantly longer TOT compared to chemotherapy, suggesting long-term benefit.
METHODS: This retrospective study of patients with NSCLC from 18 major hospitals (public, private or university teaching hospitals) enrolled in Malaysia's National Cardiovascular and Thoracic Surgical Database (NCTSD) assessed the efficacy of lower doses of afatinib on treatment outcomes in a real-world clinical practice. Data on clinical characteristics, afatinib dosing, and treatment outcomes for patients included in NCTSD from 1st January 2015 to 31st December 2020 were analyzed.
RESULTS: Of the 133 patients studied, 94.7% had adenocarcinoma. Majority of the patients (60.9%) had EGFR exon 19 deletion and 23.3% had EGFR exon 21 L858R point mutation. The mean age of patients was 64.1 years and majority (83.5%) had Eastern Cooperative Oncology Group performance status of 2-4 at diagnosis. The most common afatinib starting doses were 40 mg (37.6%), 30 mg (29.3%), and 20 mg (26.3%) once daily (OD), respectively. A quarter of patients had dose reduction (23.3%) due to side effects or cost constraints. Majority of the patients had partial response to afatinib (63.2%) whilst 2.3% had complete response. Interestingly, the objective response rate was significantly higher (72.3%) with afatinib OD doses of less than 40 mg compared to 40 mg (54.0%) (P=0.032). Patients on lower doses of afatinib were two times more likely to achieve an objective response [odds ratio =2.64; 95% confidence interval (CI): 1.20-5.83; P=0.016]. These patients had a numerically but not statistically longer median time to treatment failure (TTF). Median TTF (95% CI) for the overall cohort was 12.4 (10.02-14.78) months. Median overall survival (95% CI) was 21.30 (15.86-26.75) months.
CONCLUSIONS: Lower afatinib doses (<40 mg OD) could be equally effective as standard dose in patients with EGFR-mutant advanced NSCLC and may be more suited to Asian patients, minimizing side effects that may occur at higher dosages of afatinib leading to dose interruptions and affecting treatment outcomes.
PATIENTS AND METHODS: This multicenter, randomized, Phase 3 trial evaluated the efficacy and safety of GC followed by EBV-CTL vs. GC alone as first-line treatment for R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the United States (US) were included. Subjects were randomized to first-line GC (4 cycles) and EBV-CTL (6 cycles) or GC (6 cycles) in a 1:1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety.
CLINICALTRIALS: gov identifier: NCT02578641.
RESULTS: 330 subjects with NPC were enrolled. Most subjects in both treatment arms received ≥4 cycles of chemotherapy and most subjects in the GC+EBV-CTL group received ≥2 infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC+EBV-CTL subjects. The median OS was 25.0 months in the GC+EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% CI: 0.91, 1.56; P = 0.194). Only 1 subject experienced a Grade 2 serious adverse event related to EBV-CTL.
CONCLUSION: GC+EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS vs. chemotherapy. This is the largest adoptive T cell therapy trial reported in solid tumors to date.