Seminars in oncology最新文献

The majority of cancer clinical trials leading to therapeutic approval focus on outcomes such as objective tumor responses, progression-free survival (PFS), and overall survival (OS). However, it is equally important to assess toxicity, especially when comparing standard therapies with experimental ones. Clinical trials often fail to synthesize the relationship between efficacy and adverse event frequency, partly due to differences in measurement units. To address this, the number needed to treat (NNT) and number needed to harm (NNH) can be used as standardized measures. NNT represents the number of patients required to benefit from a treatment, while NNH indicates the number needed to experience harm. These metrics allow for a more balanced evaluation of therapeutic efficacy and toxicity. By calculating NNT for PFS or OS and NNH for adverse events, we can assess the therapeutic benefit relative to potential harm. The likelihood of being helped or harmed (LHH) combines these metrics into a ratio that expresses the balance between benefit and toxicity. Ideally, LHH values greater than 1 indicate a favorable balance toward efficacy. Though LHH has been applied mainly to psychotropic drugs, it was used in oncology sometimes. For example, studies in advanced non-small cell lung cancer and breast cancer have demonstrated LHH's utility in comparing treatments. Whereas LHH calculation has some limitations, it offers a valuable tool for explaining treatment risks and benefits to patients. It also could guide clinical trial design in cancer therapy.

Background: Small-cell lung cancer (SCLC) accounts for 10%-15% of all lung cancers. At diagnosis, nearly two thirds of patients with SCLC have extensive stage (ES), with a median overall survival (OS) less than 12 months. The combination of protein-death-1/protein-death-ligand-1 (PD-1/PD-L1) immune checkpoint inhibitors (ICIs) with first-line platinum plus etoposide chemotherapy has changed the therapeutic landscape for ES-SCLC. Older adults represent most of the cancers diagnosed and deaths by age group, with an expected increase over the next decade. In the real-world setting, about 30%-40% of patients with a diagnosis of SCLC are reported to be over 70-years-old at the time of diagnosis. However, this subgroup of patients is underrepresented in clinical trials. Based on this evidence, we performed this systematic review to define the activity of ICIs plus chemotherapy in older patients with previously untreated ES-SCLC.

Methods: This systematic review was carried out in accordance with the statement in the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search on multiple electronic databases was conducted from inception to the end of April to identify randomized trials that prospectively evaluated chemotherapy ± PD-1/PD-L1 ICIs. When more than one report of the same study was available, the most recent data (with longer follow-up and/or higher number of patients) was considered. The primary endpoint of the study was efficacy, in terms of overall survival, progression-free survival, and disease control rate.

Results: We selected six randomized clinical trials that enrolled 3396 patients in the meta-analysis. In the experimental arm, 670 patients were 65 years of age and older compared to 504 in the control arm. In the subgroup of patients ≥65 years, adding ICIs to chemotherapy led to a significant benefit in OS [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.72-0.90). There was moderate but not-significant heterogenity among the trials (I² = 47%, P = 0.07).

Conclusion: This systematic review found that the combination of chemotherapy plus ICIs improved OS among older patients with ES-SCLC. Biomarker and comprehensive geriatric assessment are needed to improve the identification and selection of patients with cancer that are uniformly defined as older.

Objectives: We previously showed that men with melanoma harboring BRAF mutations had significantly lower benefit from targeted therapy as compared with women Here we explored the hypothesis that such gender-based dimorphism in the efficacy of BRAF-pathway blockade extends to other tumor histotypes carrying pathogenic BRAF-mutations.

Methods: We retrospectively analyzed data from a cohort of patients with advanced colorectal-cancer (CRC) harboring BRAF V600E mutations, treated with anti-EGFR/BRAF/MEK targeted therapy. The primary objective was to assess the association between gender and outcome of patients treated with targeted therapy, in terms of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).A multivariable Cox proportional hazard regression model was used to assess the association between gender and PFS and OS, adjusted for other relevant clinical, pathological and molecular prognostic factors, including ECOG PS (0 vs 1-2), primary tumor site (right-side vs left-side), microsatellite instability status (instable [MSI] vs stable [MSS]), number of metastatic sites at treatment start, treatment type (double targeted therapy [ie, anti-EGFR + anti-BRAF] vs triple targeted therapy [ie, anti-EGFR + anti-BRAF + anti-MEK]) and mutational status of the RNF43 gene (wild type vs mutated).

Results: Ninety-eight patients with advanced CRC were included in the analysis: 59 (60%) were women and 39 (40%) men. The ORR was 43.1% in women vs only 23.7% in men (p-value = .05). Multivariable analysis adjusted for relevant clinical, pathological, and molecular variables associated with patients' prognosis, showed a significantly shorter PFS and OS in men as compared with women: the adjusted-HR was, respectively, 1.65 (95%CI,1.00-2.69; p = .04) for PFS and 1.83 (95%CI,1.08-3.08; p-value = .02) for OS.

Conclusions: We confirmed a significant gender-based dimorphism in the efficacy of anti-EGFR/BRAF/MEK therapy in patients with advanced-CRC harboring BRAF mutations that warrant further investigation.