Background/Aim: Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAF V600E -mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. V600E -mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland. Patients and Methods: Anonymized data from BRAF V600E -mutant mCRC patients were analyzed retrospectively regarding 1 st -, 2 nd -and 3 rd -line treatment using descriptive statistics. Results: Forty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with rightsided tumors. Most patients (81.0%) were tested for BRAF before 1 st -line. Four patients (9.5%) showed high microsatellite instability (MSI-H). Based on 94 treatment lines, chemotherapy combined with targeted therapy (TT) was used mostly (61.7%),
Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data. This retrospective analysis was designed to evaluate (approved) therapeutic approaches and algorithms in BRAF
Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 have shifted the treatment paradigm of advanced non-small cell lung cancer (NSCLC), but responses are often heterogeneous and temporary. Several landmark publications have confirmed the dominant role of gut microbiome in modulating tumor responses to ICIs, suggesting the predictive value of antibiotics (ATB) in patients treated with anti-PD-(L)1 antibody. However, more evidence is needed to comprehensively reveal the association between ATB usage and ICIs therapeutic response in NSCLC, especially in Chinese populations. Method: We retrospectively reviewed the medical records of patients with advanced/metastatic NSCLC received anti-PD-(L)1 based therapies at our hospital. Detailed clinicopathologic characteristics, response data and ATB usage were collected for all patients. The patients receiving ATB within one month around the first administration of ICIs (defined as ATB-treated) were compared to those without (ATB-untreated). Result: 109 cases receiving anti-PD-(L)1 based therapies and underwent response evaluation were identified. 65 (59.3%) of them received monotherapy and 44 received combination therapies including anti-PD-(L)1 plus anti-angiogenesis/chemotherapy. 35 (32.1%) patients had been prescribed ATB 60 days before or during the course of ICIs treatment, and 20 (18.3%) were categorized as ATB-treated group. The most commonly administered ATB were b-lactam inhibitors, fluoroquinolones and macrolides. No major statistical differences in baseline clinicopathologic features were observed between ATB-treated and -untreated groups. The objective response rates (ORR) to ICIs in two groups were 65% and 82%, respectively. ATB treatment was significantly associated with shorter progression-free survival (PFS) (median 3.73 vs 9.3 m, p<0.001), and also tended to be associated with primary disease progression (35% vs 18%, p¼0.087). The overall survival (OS) (median 31.9 vs 37.6 m, p¼0.74) was similar in two groups, but ATB appeared to be related to decreased duration of survival from ICI treatment start to death (median 6.07 vs 26.9 m, p¼0.002). In multivariable analysis, ATB treatment was markedly associated with poorer ORR and survival to ICIs after adjusting for prior line treatment setting, ICI regimens, numbers of ICI-related toxicity and clinical characteristics. Conclusion: ATB usage was a predictor for decreased clinical benefit from anti-PD-(L)1immunotherapies in Chinese NSCLC patients. More comprehensive understanding of the interaction between gut microbiome and ATB is still in urgent need. Furthermore, modulating ATB-related gut microbiome dysbiosis may enhance response to anti-PD-(L)1 immunotherapies.Background: The phase III trials of nivolumab, pembrolizumab or atezolizumab in comparison to standard chemotherapy for advanced non-small cell lung cancer (NSCLC) included a small number of patients with brain metastases. The aim of this study was to evaluate the radiological features of brain metastases after treatment with radiotherapy (...
Line 2+ 16.1 months, p¼0.01, HR¼0.55). There was no significant difference in reasons for immunotherapy discontinuation, such as toxicity or progression (p¼0.888). Age remained not a significant predictor of survival (p¼0.886), after controlling for the other variables (gender, ICPI regimen, therapy line, ECOG, risk group).Conclusions: Patients with mRCC !70 were less likely to be treated with combination ICPI and more likely to be treated with ICPI in 2 nd or later lines of therapy. Despite this, there was no difference in OS, or rates of treatment discontinuation for either toxicity or progression in an unselected, real world patient cohort. This data supports the consideration of ICPI in patients !70.
Background: The PARAMOUNT trial established maintenance therapy with pemetrexed (P) in patients with advanced, nonsquamous NSCLC. The AVAPERL trial demonstrated encouraging results with bevacizumab (B) plus P, compared with B alone. Methods: We conducted a nonrandomized phase II trial with two sequential cohorts to compare maintenance therapy with B+P versus P. In the first cohort, 77 patients were treated with 4 cycles of cisplatin 75 mg/m2, P 500 mg/m2 and B 7.5 mg/kg every 3 weeks, followed by B+P maintenance until RECIST progression (Clin Lung Cancer 2015). We expanded the trial by a second cohort, and treated 52 patients with the same chemotherapy, but without B. Here, we present for the first time a comparison of the two cohorts. Inclusion and exclusion criteria and follow up were the same. The primary endpoint was progression-free survival (PFS). Other outcomes of interest were overall survival (OS), overall response (OR), adverse events (AE), and treatment cost.
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