Immunotherapy plus chemotherapy for patients with EGFR-mutated non-squamous cell lung cancer for disease progression after EGFR tyrosine-kinase inhibitor: A meta-analysis of randomized controlled trials.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations face poor outcomes after progression on tyrosine kinase inhibitors (TKIs). The efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy in these patients remains uncertain. METHODS: We searched for studies published between randomized controlled trials of ICIs in combination therapies in advanced NSCLC patients post EGFR TKI progression. Data on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were extracted and analyzed. RESULTS: Six studies with a total of 2,225 patients were analyzed. The pooled hazard ratio (HR) for PFS was 0.60 (95% CI, 0.55 - 0.65; P < 0.0001), indicating a significant improvement in PFS with ICIs. Subgroup analysis suggested that patients with prior exposure to third-generation TKIs showed a more pronounced benefit (HR = 0.61; 95% CI, 0.49 - 0.76; P < 0.0001). However, no benefit was found in patients without prior exposure. The efficacy of the experimental interventions was also shown on the pooled estimates of OS (HR = 0.87; 95% CI, 0.77 - 0.0.99; P value = 0.04) and ORR (OR = 1.91; 95% CI, 1.32 - 2.76; P <0.0001). CONCLUSIONS: ICIs may significantly benefit PFS among patients with EGFR-mutated NSCLC who have progressed on TKI treatment. Future research should continue stratifying patients based on prior treatment exposure to optimize therapeutic strategies.

Poly(ADP-ribose) polymerase inhibitors as maintenance treatment in patients with newly diagnosed advanced ovarian cancer: a meta-analysis.

Aim: Poly(ADP-ribose) polymerase inhibitors (PARPIs) improved progression-free survival among patients with recurrent ovarian cancer. This meta-analysis examined the effectiveness of PARPIs as maintenance strategy for newly diagnosed patients with advanced high-grade ovarian cancer with or without mutations. Materials & methods: Using defined selection criteria, a literature search identified four eligible randomized clinical trials involving 2386 patients. Results: Compared with placebo maintenance, PARPIs achieved a 46% reduction in the risk of progression or death as compared with placebo (hazard ratio: 0.54; 95% CI: 0.39-0.73; p < 0.0001). That benefit was shown in all clinical subgroups: among those with BRCA mutation, with negative/unknown BRCA mutation, and in those with homologous recombination deficient tumors. Data about the effect on overall survival are still premature. Conclusion: In patients with newly diagnosed advanced ovarian cancer, PARPIs maintenance after standard therapy achieved a significant improvement in progression-free survival as compared with placebo, overall and in all subgroups.

Correlation Between Oncotype Dx Recurrence Score and PREDICT Estimates in Early Breast Cancer: A Single Institution Experience.

PURPOSE: Oncotype Dx Recurrence Score (RS) is prognostic and predictive of chemotherapy benefit in women with node-negative and node-positive in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer. Nevertheless, its direct cost may be inhibitive. This study assesses the correlation between the RS and the free online PREDICT tools' estimations of adjuvant chemotherapy benefit. PATIENTS AND METHODS: A retrospective review of the electronic medical records of 112 patients with tumors tested for the RS and the PREDICT tool was used to estimate survival benefits. The correlation between RS and PREDICT estimations was analyzed using Spearman rank and McNemar tests. RESULTS: The median age of patients was 53 (95% CI, 50 to 55) years, with most patients having negative axillary lymph nodes (78%). While the absolute value for RS showed significant positive correlations with adjuvant chemotherapy's benefit as estimated by PREDICT, no significant correlations were found between the two methods in the percentage of chemotherapy gain. Notably, discordance rates between 48% and 67% between RS-based risk assignments and those based on PREDICT estimates were significant across the study population and subgroups. Only one disease recurrence and one breast cancer-related death were documented over a median follow-up of 23.5 (95% CI, 19.8 to 27.2) months. CONCLUSION: Our findings highlight a significant discordance between RS and PREDICT tools in predicting the benefits of adjuvant chemotherapy in patients with HR+, HER2- early breast cancer. While both tools aim to personalize cancer treatment, their discordance varies, suggesting that PREDICT could not substitute RS to predict adjuvant chemotherapy benefits regardless of patient risk classification. Further studies are needed to explore these relationships and optimize precision medicine approaches in breast cancer management.

Extended adjuvant endocrine therapy in early breast cancer: a meta-analysis of published randomized trials.

Adjuvant endocrine therapy for 5 years is the standard adjuvant treatment for estrogen receptor-positive breast cancer while the benefits of extended adjuvant endocrine therapy (EAET) beyond 5 years are still controversial. That controversy prompted this meta-analysis to compare 5 years of adjuvant endocrine therapy only versus EAET. Eligible 11 randomized, controlled trials comprising 29,000 women were included. EAET showed no advantage in overall survival (OS) from all causes mortality (odds ratio [OR] = 0.98 (95% confidence interval [CI], 0.87-1.09); P = 0.67). On the other hand, compared with standard therapy, the pooled effects showed that EAET was associated with improvement in breast cancer-specific survival (OR = 0.87; 95% CI 0.79-0.96; P = 0.004), disease-free survival (DFS) (OR = 0.87; 95% CI 0.75-0.99; P = 0.002), disease recurrence (OR = 0.76; 95% CI 0.64-0.90; P = 0.001), and contralateral breast recurrence (OR = 0.74; 95% CI 0.59-0.93; P = 0.008). Improvement in DFS or disease recurrence was not shown in studies that compared 5 years of tamoxifen versus tamoxifen beyond 5 years. Subgroup analysis showed that EAET conferred more benefit for patients with positive lymph nodes. Rates of positive lymph nodes, the study size, and the median duration of follow-up were identified as variables that explained most of the demonstrated data heterogeneity. EAET should be considered as a preferred strategy for high-risk hormone-positive early breast cancer patients with positive lymph nodes; however, the benefit on OS could not be demonstrated.