Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma.

The SCHOLAR-2 retrospective study highlighted poor overall survival (OS) with standard of care (SOC) regimens among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) who failed a covalent Bruton tyrosine kinase inhibitor (BTKi). In the ZUMA-2 single-arm trial, brexucabtagene autoleucel (brexu-cel; autologous anti-CD19 CAR T-cell therapy) demonstrated high rates of durable responses in patients with R/R MCL who had previous BTKi exposure. Here, we compared OS in ZUMA-2 and SCHOLAR-2 using three different methods which adjusted for imbalances in prognostic factors between populations: inverse probability weighting (IPW), regression adjustment (RA), and doubly robust (DR). Brexu-cel was associated with improved OS compared to SOC across all unadjusted and adjusted comparisons. Hazard ratios (95% confidence intervals) were 0.38 (0.23, 0.61) for IPW, 0.45 (0.28, 0.74) for RA, and 0.37 (0.23, 0.59) for DR. These results suggest a substantial survival benefit with brexu-cel versus SOC in patients with R/R MCL after BTKi exposure.

Increased mortality in patients with hematologic malignancies treated with proton pump inhibitors: a nationwide cohort study.

Proton Pump inhibitors (PPIs) are frequently prescribed to cancer patients to prevent gastric mucosal damage. Post-diagnostic PPI use in patients with solid tumors may be associated with increased cancer mortality. However, the hazardous impact of PPIs in patients with hematologic malignancies remains unknown. This association was investigated in a large, retrospective cohort study using data from the Danish nationwide health registries. The outcomes were cancer-specific or non-cancer deaths. We identified 15,320 patients with hematologic malignancies and of these 1811 were identified as post-diagnostic PPI users. PPI users had significantly increased HRs for cancer-specific mortality (HR 1.31; 95% CI, 1.18-1.44) and 1-year cancer-specific mortality (HR 1.50, 95% CI 1.29-1.74) as compared to nonusers. The association between PPI use and increased cancer-specific mortality in Danish patients with hematologic malignancies supports the raised concerns regarding the frequent use of PPIs in cancer patients.

Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe: The SCHOLAR-2 retrospective chart review study.

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6-20.0) in the overall cohort, 5.5 months (95% CI 3.9-8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9-30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3-12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure.

[A 87-year-old woman was run down by a hit-and-run driver and cured of malignant lymphoma].

A 87-year-old woman was run down by a hit-and-run driver while riding her bicycle. An acute computed tomography (CT) showed no fractures or internal bleedings but revealed an asymptomatic tumour in the colon transversum. During operation, a diffuse large B-cell lymphoma was resected. Subsequent positron emission tomography/CT and bone marrow examination revealed no dissemination. No chemotherapy or radiation therapy was given. The patient was seen in the outpatient clinic every six months, and after two and a half year she is still in complete remission with a normal haemoglobin level.

Insulin-like growth factor receptor 1 mRNA expression as a prognostic marker in advanced non-small cell lung cancer.

BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) has yet to be established as a biomarker in non-small cell lung cancer (NSCLC) but could prove useful in customized chemotherapy. We explored its prognostic value using both quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). MATERIALS AND METHODS: Analyses of IGF1R were performed on patients with advanced NSCLC, included in a randomized chemotherapy trial, having large, representative tissue samples. IGF1R mRNA and protein expression were correlated to clinical end-points. RESULTS: Surgical tissue samples were available from 33 patients deemed inoperable. IGF1R status varied according to histopathology. Patients with tumors positive for IGF1R mRNA expression had a shorter progression-free and overall survival when compared to the negative sub-group (6.1 vs. 7.4 months, p=0.039 and 10.9 vs. 14.3 months, p=0.038, respectively). IGF1R protein expression showed a similar, although non-significant tendency. CONCLUSION: IGF1R mRNA expression may be a prognostic biomarker in advanced NSCLC and should be investigated in a larger population.

Class III ß-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial.

PURPOSE: Platinum-based doublets are the cornerstone of treatment in advanced non-small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III ß-tubulin (TUBB3) has been shown of value in NSCLC, but evidence is not uniform. Accordingly, we explored the predictive role of TUBB3 in advanced NSCLC. EXPERIMENTAL DESIGN: Four hundred forty-three patients with advanced NSCLC were enrolled in a phase III trial and randomized to vinorelbine- or paclitaxel-containing chemotherapy. Immunohistochemical evaluation of TUBB3 status was mainly done on bioptic material and correlated to response rates, progression-free survival (PFS), overall survival (OS), quality of life (QOL), and toxicity. RESULTS: Two hundred sixty-one (58.9%) patients had representative tissue samples for TUBB3 evaluation. Patients with TUBB3-negative adenocarcinomas had a significantly prolonged PFS and OS when compared with the opposite subgroup (7.87 vs. 6.83 months, P = 0.035 and 14.17 vs. 11.17 months, P = 0.018, respectively). Multivariate analyses revealed an HR of 1.55 (95% CI, 1.04-2.31, P = 0.032) for TUBB3-positive adenocarcinoma patients. TUBB3-negative adenocarcinoma patients showed a mean QOL decline of -18.25 points (95% CI, -4.28 to -32.22, P = 0.013) as compared with -3.86 (95% CI, -7.0 to 15.52, P = 0.5). CONCLUSION: TUBB3 was of predictive value in adenocarcinoma patients in the largest, randomized advanced NSCLC population published to date. It may be clinically useful in conjunction with other biomarkers, but QOL information should be recorded during validation, as prophylactic intervention may be needed in specific subgroups at risk of toxicity.

ERCC1, toxicity and quality of life in advanced NSCLC patients randomized in a large multicentre phase III trial.

AIM: Excision repair cross complementation group 1 (ERCC1) is a promising biomarker in advanced non-small cell lung cancer (NSCLC). However, current evidence regarding the impact of ERCC1 on toxicity and quality of life (QOL) is limited. PATIENTS AND METHODS: Four hundred and forty three patients with advanced NSCLC were enroled in a phase III trial and randomized to triplet chemotherapy or standard doublet regimen. Immunohistochemical evaluation for ERCC1-status was mainly performed on bioptic material. Toxicity and patient-reported QOL were correlated to ERCC1-status. RESULTS: We observed a significantly improved outcome in patients with ERCC1-negative (ERCC1-neg) tumours and demonstrated interaction between ERCC1-status and adenocarcinomas. Numerically more toxicity was observed in the entire population of ERCC1-neg tumours and reached significance in patients with adenocarcinomas regarding leukopenia (P=0.015), nausea/vomiting (P=0.040) and neurotoxicity (P=0.037). Mean change in QOL in the entire population was -13.33 (ERCC1-neg; P=0.001) and -2.25 (ERCC1-positive (ERCC1-pos): P=0.607) and -14.86 (ERCC1-neg; P=0.006) and 0 (ERCC1-pos) in patients with adenocarcinomas. CONCLUSIONS: Patient-reported QOL deteriorated significantly among survival-favourable ERCC1-neg patients possibly due to increased toxicity especially in patients with adenocarcinomas. Our novel findings emphasise strict demands for careful patient selection, proper methodology and prospective validation of ERCC1 to prove a true survival benefit before clinical implementation.

Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature.

BACKGROUND: Patients diagnosed with advanced non-small cell lung cancer have a dismal prognosis and are often relative resistant to chemotherapy. A need for markers has emerged based on tumour biology in order to predict which patients will respond to treatment. Excision repair cross-complementation group 1 (ERCC1) has shown potential as a predictive marker in patients with NSCLC treated with cisplatin-based chemotherapy. Carboplatin has gained widespread use in the treatment of advanced NSCLC and its mechanisms of action are likely similar to that of cisplatin. MATERIALS AND METHODS: A literature review on ERCC1 was conducted as predictor in NSCLC patients receiving platinum-based treatment with emphasis on carboplatin. English language publications from January 1996 to February 2008 were eligible and data on methodology and outcome were recorded. RESULTS: Eight preclinical articles, 25 clinical articles and 1 clinical abstract were identified. Laboratory methods were mainly RT-PCR (reverse transcriptase polymerase chain reaction) or immunohistochemistry (IHC) for expression of ERCC1. Preclinical studies pointed towards similar mechanisms of chemotherapy-resistance among platinum compounds. A statistically significant benefit in outcome was found among NSCLC patients, who received adjuvant treatment, and had low-ERCC1 expression. Advanced NSCLC patients treated with cisplatin showed improved response rates (RR) but no difference in other endpoints. Studies on advanced NSCLC patients treated with carboplatin were sparse, heterogeneous and small thus reporting varying results. CONCLUSION: The literature on advanced NSCLC patients treated with carboplatin or cisplatin are dominated by small and heterogeneous patient populations and yielded different results. No firm conclusions can be drawn on carboplatin based on the current literature. Research on the development of a reliable methodology is warranted followed by validation in large, prospective, randomized trials as ERCC1 may possibly play an important role as tumour marker in tailored chemotherapy for NSCLC.

Prognosis of small bowel adenocarcinoma treated with Mayo or Xelox regimen: a matched case-control study from a database of 581 patients with colorectal cancer.

The purpose of this study was to compare the effects of chemotherapy on the prognosis for patients with adenocarcinoma of the small bowel (SBC) and colorectal cancer (CRC). A case-control study was conducted, comprised of 13 SBC cases treated palliatively (n=7) following surgery with capecitabine monotherapy (Xeloda) combined with oxaliplatin (Xelox), or with adjuvant 5-fluorouracil chemotherapy (Mayo) (n=6). The control group was selected from a database of 581 patients with CRC, with each SBC case being matched to 5 CRC controls. In the palliative group, response rates (RR) for SBC patients were 14%, compared to 35% for CRC patients (p=0.08). Median progression-free survival (PFS) times were 4 and 6 months (p=0.8) and median overall survival (OS) times were 8.4 and 16.4 months (p=0.9) for SBC and CRC patients, respectively. In the adjuvant group, the recurrence-free survival rates were 66 and 89% (p=0.6) after 1 year and 66 and 71% (p=0.7) after 3 years. Three-year overall survival rates were 80 and 80% (p=0.3) in the palliative group, and 80 and 66% (p=0.4) in the adjuvant group. Standard chemotherapy regimes seemed less effective on SBC than on CRC patients, and had a less favorable prognosis. However, reliable conclusions cannot be drawn from a small patient population, and multicentre studies are needed.

Adjuvant chemotherapy in elderly patients (>or=75 yr) completely resected for colon cancer stage III compared to younger patients: toxicity and prognosis.

PURPOSE: To compare benefits and risks to adjuvant chemotherapy following complete resection of node-positive colon cancer stage III for patients aged >or=75 yr and younger. METHOD: A retrospective study compared recurrence-free and overall survival, toxicity, and dose intensity of adjuvant bolus 5-FU according to the Mayo regimen chemotherapy in consecutive patients aged 19-74 (n=203) and >or=75 yr (n=24). RESULTS: The estimated 5-yr proportional survival rates were 0.65 for patients age less than 75 yr compared to 0.65 (p=0.96) for elderly. The frequencies of anemia (0%), thrombocytopenia (0%), leukopenia (4%), infection (8%), vomiting (0%), mucositis (17%), diarrhea (13%) CTC grade 3 or 4 toxicity in elderly patients were not significantly different from that in younger patients (p > 0.05). Significantly more elderly (8%) had a decline in performance status to grade 3 or 4, as compared to younger patients (4%) (p=0.002). 5-FU dose reduction was necessary for significantly more elderly (51%) as compared to younger patients (28%) (p=0.02), and fewer elderly (54%) completed the scheduled six treatment courses as compared to younger patients (82%) (p=0.05). CONCLUSIONS: Adjuvant 5-FU chemotherapy should be considered for elderly patients aged >or=75 yr in good performance at high risk of recurrence of colon carcinoma after resection.