Bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: A meta-analysis of individual patients' data from 3 phase III studies.

The real impact of bevacizumab maintenance as single agent in metastatic colorectal cancer (mCRC) remains unclear. SAKK-41/06 and PRODIGE-9 failed to demonstrate the non-inferiority and superiority of bevacizumab versus no maintenance, respectively, while AIO-KRK-0207 showed the non-inferiority of maintenance bevacizumab versus bevacizumab and fluoropyrimidines for time to strategy failure.Bibliography electronic databases (PubMed, MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials) were searched for English published clinical trials prospectively randomizing mCRC patients to receive bevacizumab maintenance or not after first-line chemotherapy plus bevacizumab. Individual patients' data (IPD) were provided by investigators for all included trials. Primary end-points were progression-free survival (PFS) and overall survival (OS), both from the start of induction and maintenance. Univariate and multivariate analyses for PFS and OS were performed.Three phase III studies - PRODIGE-9, AIO-KRK-0207 and SAKK-41/06 - were included. Considering the different timing of randomization, IPD of patients not progressed during induction and starting maintenance phase entered the analysis. 909 patients were included, 457 (50%) received bevacizumab maintenance. Median PFS from induction start was 9.6 and 8.9 months in bevacizumab group versus no maintenance group, respectively (HR 0.78; 95%CI: 0.68-0.89; p 0.0001). Subgroups analysis for PFS showed a significant interaction according for RAS status (p = 0.048), with a maintenance benefit limited to RAS wild-type patients. No difference in terms of OS was observed.Despite the statistically significant PFS improvement for bevacizumab maintenance, the absolute benefit appears limited. Subgroup analysis shows a differential effect of bevacizumab maintenance in favor of RAS wild-type patients. Considering these results, maintenance therapy with fluoropyrimidine with or without bevacizumab remains the first option. Single agent bevacizumab maintenance can be considered in selected cases, such as cumulative toxicity or patient's refusal, in particular for RAS wild-type patients

Is Computed-Tomography-Based Body Composition a Reliable Predictor of Chemotherapy-Related Toxicity in Pancreatic Cancer Patients?

BACKGROUND Malnutrition, loss of weight and of skeletal muscle mass are frequent in pancreatic cancer patients, a majority of which will undergo chemotherapy over the course of their disease. Available data suggest a negative prognostic role of these changes in body composition on disease outcomes; however, it is unclear whether tolerance to chemotherapeutic treatment is similarly and/or negatively affected. We aimed to explore this association by retrospectively assessing changes in body composition and chemotherapy-related toxicity in a cohort of advanced pancreatic cancer patients. METHODS Body composition was evaluated through clinical parameters and through radiological assessment of muscle mass, skeletal muscle area, skeletal muscle index and skeletal muscle density; and an assessment of fat distribution by subcutaneous adipose tissue and visceral adipose tissue. We performed descriptive statistics, pre/post chemotherapy comparisons and uni- and multivariate analyses to assess the relation between changes in body composition and toxicity. RESULTS Toxicity risk increased with an increase of skeletal muscle index (OR: 1.03) and body mass index (OR: 1.07), whereas it decreased with an increase in skeletal muscle density (OR: 0.96). Multivariate analyses confirmed a reduction in the risk of toxicity only with an increase in skeletal muscle density (OR: 0.96). CONCLUSIONS This study suggests that the retrospective analysis of changes in body composition is unlikely to be useful to predict toxicity to gemcitabine-nab-paclitaxel

Comprehensive Treatment Algorithms of the Swiss Peritoneal Cancer Group for Peritoneal Cancer of Gastrointestinal Origin

Peritoneal cancer (PC) is a dire finding, yet in selected patients, long-term survival is possible. Complete cytoreductive surgery (CRS) together with combination immunochemotherapy is essential to achieve cure. Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are increasingly added to the multimodal treatment. The Swiss Peritoneal Cancer Group (SPCG) is an interdisciplinary group of expert clinicians. It has developed comprehensive treatment algorithms for patients with PC from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include multimodal neoadjuvant treatment, surgical resection, and palliative care. The indication for and results of CRS HIPEC and PIPAC are discussed in light of the current literature. Institutional volume and clinical expertise required to achieve best outcomes are underlined, while inclusion of patients considered for CRS HIPEC and PIPAC in a clinical registry is strongly advised. The present recommendations are in line with current international guidelines and provide the first comprehensive treatment proposal for patients with PC including intraperitoneal chemotherapy. The SPCG comprehensive treatment algorithms provide evidence-based guidance for the multimodal care of patients with PC of gastrointestinal origin that were endorsed by all Swiss clinicians routinely involved in the multimodal care of these challenging patients

Retrospective Analysis of Treatment Pathways in Patients With BRAFV600E-mutant Metastatic Colorectal Carcinoma - MORSECRC.

BACKGROUND/AIM Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFV600E-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. 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 BRAFV600E-mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland. PATIENTS AND METHODS Anonymized data from BRAFV600E-mutant mCRC patients were analyzed retrospectively regarding 1st-, 2nd- and 3rd-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 right-sided tumors. Most patients (81.0%) were tested for BRAF before 1st-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%), followed by chemotherapy alone (19.1%). Backbone therapies were most frequently FOLFOXIRI (27.7%), FOLFOX/CAPOX (22.3%), or FOLFIRI (20.2%). Anti-VEGF/VEGFR and anti-EGFR-treatments were used in 45.7% and 23.4% of patients, respectively. Across all treatment lines and types, the predominantly documented reason for discontinuation was lack of efficacy. CONCLUSION Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAFV600E-mutated mCRC treatment prior to approval of the targeted combination encorafenib plus cetuximab. Since lack of efficacy was the major reason for treatment discontinuation, newly approved therapies including encorafenib plus cetuximab and - for MSI-H tumors - pembrolizumab represent urgently needed options for future mCRC patients

Outcome and Prognostic Factors of COVID-19 Infection in Swiss Cancer Patients: Final Results of SAKK 80/20 (CaSA).

PURPOSE These are the final results of a national registry on cancer patients with COVID-19 in Switzerland. METHODS We collected data on symptomatic COVID-19-infected cancer patients from 23 Swiss sites over a one-year period starting on 1 March 2020. The main objective was to assess the outcome (i.e., mortality, rate of hospitalization, ICU admission) of COVID-19 infection in cancer patients; the main secondary objective was to define prognostic factors. RESULTS From 455 patients included, 205 patients (45%) had non-curative disease, 241 patients (53%) were hospitalized for COVID-19, 213 (47%) required oxygen, 43 (9%) invasive ventilation and 62 (14%) were admitted to the ICU. Death from COVID-19 infection occurred in 98 patients, resulting in a mortality rate of 21.5%. Age ≥65 years versus <65 years (OR 3.14, p = 0.003), non-curative versus curative disease (OR 2.42, p = 0.012), ICU admission (OR 4.45, p < 0.001) and oxygen requirement (OR 20.28, p < 0.001) were independently associated with increased mortality. CONCLUSIONS We confirmed high COVID-19 severity and mortality in real-world cancer patients during the first and second wave of the pandemic in a country with a decentralized, high-quality, universal-access health care system. COVID-19-associated mortality was particularly high for those of older age in a non-curative disease setting, requiring oxygen or ICU care

Letrozole as upfront endocrine therapy for postmenopausal women with hormone-sensitive breast cancer: BIG 1-98

The BIG 1-98 trial is a large, randomized, independently conducted clinical trial designed to compare the efficacy of upfront letrozole versus tamoxifen monotherapy and to compare sequential or up-front use of letrozole and/or tamoxifen as an early adjuvant therapy for patients with early breast cancer. We report on the results from the primary core analysis of the BIG 1-98 trial of 8,010 patients, which compares monotherapy with letrozole versus tamoxifen. This pre-planned core analysis allowed the use of patient data from the monotherapy arms of letrozole and tamoxifen and from the sequential arms prior to the drug switch point. Patients randomized to letrozole had a 19% improved disease-free survival (hazard ratio [HR] = 0.81; P = 0.003), due especially to reduced distant metastases (HR = 0.73; P = 0.001). A 14% risk reduction of fatal events in favor of letrozole was also observed (P = NS). The results from the monotherapy arms alone confirmed the findings from the primary core analysis. Based on the results from this trial, the aromatase inhibitor letrozole (Femara®) is currently recommended as a part of standard adjuvant therapy for postmenopausal women with endocrine-responsive breast cancer and has recently been approved in the early adjuvant setting in both Europe and the United States. A subsequent analysis after additional follow-up will address the question of monotherapy versus sequential therapy