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Background: Prognostic factors of metastatic rectal cancer are not well known., Aim: The objective of this study was to identify prognostic factors of overall survival (OS) in a cohort of patients with non-resectable synchronous metastatic rectal cancer., Methods: Patients were retrospectively enrolled from 18 French centres. Univariate and multivariate analyses were performed to identify prognostic factors for OS. A simple score was derived from this a development cohort RESULTS: A total of 243 patients with metastatic rectal cancer were included in the study. Median OS was 24.4 months, 95% CI [19.4-27.2]. Among patients with non-resected metastases (n=141), six independent prognostic factors associated with better OS were identified in multivariate analysis: primary tumour surgery, WHO score 0-1, middle or upper rectal tumour, lung metastases only, systemic chemotherapy and targeted agent in first line. A prognostic score individualized three groups, each factor counting for one point in the score (<3, = 3 et > 3). Their median OS were respectively 27.9 months, 95% CI [21.7-35.1], 17.1 months [11.9-19.7] (HR 2/1 =2.08, 95%, CI [1.31-3.30], p 2/1 =0.002) and 9.1 months [4.9-11.7] (HR 3/2 =2.32, 95% CI [1.38-3.92], p 3/2 =0.001)., Conclusion: A prognostic score for non-resectable synchronous metastatic rectal cancer can be proposed to classify patients in three prognostic groups., Competing Interests: Conflict of interest None declared., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population., Methods: In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation. The primary end point was the objective response by independent review among patients who had undergone at least 9 months of follow-up. The response was also analyzed according to whether the presence of a MET exon 14 skipping mutation was detected on liquid biopsy or tissue biopsy., Results: As of January 1, 2020, a total of 152 patients had received tepotinib, and 99 patients had been followed for at least 9 months. The response rate by independent review was 46% (95% confidence interval [CI], 36 to 57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was similar regardless of the previous therapy received for advanced or metastatic disease. Adverse events of grade 3 or higher that were considered by investigators to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Adverse events led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment., Conclusions: Among patients with advanced NSCLC with a confirmed MET exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients. Peripheral edema was the main toxic effect of grade 3 or higher. (Funded by Merck [Darmstadt, Germany]; VISION ClinicalTrials.gov number, NCT02864992.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: The use of web-based monitoring for lung cancer patients is growing in interest because of promising recent results suggesting improvement in cancer and resource utilization outcomes. It remains an open question whether the overall survival (OS) in these patients could be improved by using a web-mediated follow-up rather than classical scheduled follow-up and imaging., Methods: Advanced-stage lung cancer patients without evidence of disease progression after or during initial treatment were randomly assigned in a multicenter phase III trial to compare a web-mediated follow-up algorithm (experimental arm), based on weekly self-scored patient symptoms, with routine follow-up with CT scans scheduled every three to six months according to the disease stage (control arm). In the experimental arm, an alert email was automatically sent to the oncologist when self-scored symptoms matched predefined criteria. The primary outcome was OS., Results: From June 2014 to January 2016, 133 patients were enrolled and 121 were retained in the intent-to-treat analysis; 12 deemed ineligible after random assignment were not subsequently followed. Most of the patients (95.1%) had stage III or IV disease. The median follow-up was nine months. The median OS was 19.0 months (95% confidence interval [CI] = 12.5 to noncalculable) in the experimental and 12.0 months (95% CI = 8.6 to 16.4) in the control arm (one-sided P = .001) (hazard ratio = 0.32, 95% CI = 0.15 to 0.67, one-sided P = .002). The performance status at first detected relapse was 0 to 1 for 75.9% of the patients in the experimental arm and for 32.5% of those in the control arm (two-sided P < .001). Optimal treatment was initiated in 72.4% of the patients in the experimental arm and in 32.5% of those in the control arm (two-sided P < .001)., Conclusions: A web-mediated follow-up algorithm based on self-reported symptoms improved OS due to early relapse detection and better performance status at relapse., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-naïve or pretreated patients with non-small cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup., Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0-1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve ×6) and paclitaxel (200 mg/m(2)) every 3 weeks (B + CP), or second-line bevacizumab plus erlotinib (150 mg/d; B + E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B + CP) or more than two (B + E) intracranial hemorrhages., Results: In first-line B + CP cohort (n = 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7-7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n = 24), efficacy results for the second-line B + E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0-8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae., Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases., (©2015 American Association for Cancer Research.)

The role of T(H)17 cells in cancer is being investigated, but the existence of tumor antigen-specific T(H)17 cells has yet to be ascertained. Here, we report the first description of a spontaneous T(H)17 (IL-17(+)) response to the important tumor antigen MAGE-A3, which occurred concurrently with a T(H)1 (IFN-γ(+)) response in a lung cancer patient. MAGE-A3-specific interleukin (IL)-17(+) T cells were mainly CCR7(+) central memory T cells, whereas IFN-γ(+) cells were enriched for CCR7(-) effector memory T cells. An assessment of the fine specificity of antigen recognition by these T cells indicated that the CCR6(+)CCR4(+) and CCR6(+)CXCR3(+) fractions contained the same T(H)17/T(H)1 population at early and late differentiation stages, respectively, whereas the CCR6(-)CXCR3(+) fraction contained a distinct T(H)1 population. These findings are important because they suggest a differentiation model in which tumor antigen-specific CD4(+) T cells that are primed under T(H)17 polarizing conditions will progressively convert into IFN-γ-secreting cells in vivo as they differentiate into effector T cells that can effectively attack tumors.

Background: Data issued from the survival outcome in the ANITA trial are reported according to histology in observation (n=433) and adjuvant chemotherapy arms (n=407)., Methods: In the ANITA trial, patients with resected stage IB, stage II and stage IIIA NSCLC were randomly assigned to vinorelbine plus cisplatin or to observation. In this retrospective analysis, Kaplan-Meier plots and life tables were used to describe survival within each treatment arm and each histological subgroup: observation adenocarcinoma, observation non-adenocarcinoma, chemotherapy adenocarcinoma, chemotherapy non-adenocarcinoma., Results: In the observation arm, adenocarcinoma appears to be a poor prognostic factor in patients with resected NSCLC with a median survival of 37.3 months and 45.5 months for non-adenocarcinoma. In the treatment arm, adenocarcinoma may be a predictive factor of efficacy for adjuvant chemotherapy with a larger benefit from adjuvant vinorelbine-cisplatin chemotherapy, even though other histological subtypes also benefit from this treatment. The absolute benefit on survival at 5-years of chemotherapy was 13.9% in adenocarcinoma and 5.8% in non-adenocarcinoma., Conclusion: Efficacy of vinorelbine-cisplatin in adjuvant setting is independent from histology. The poor outcome of adenocarcinoma found in the observation arm was reversed by the positive impact of chemotherapy, possibly due to a higher chemosensitivity of this subtype., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Vinflunine (Javlor) has shown significant antitumour activity in advanced non-small cell lung cancer (NSCLC). We propose to define the recommended dose of vinflunine in combination with gemcitabine for treatment of advanced NSCLC in chemonaive patients., Methods: A phase I and pharmacokinetic study was conducted to determine the maximum tolerated dose and to establish the recommended dose of vinflunine (VFL) administered on day 1 every 21 days combined with gemcitabine given on days 1 and 8 every 3 weeks., Results: Nineteen patients were included in this study. Three patients experienced a dose limiting toxicity, with constipation in one patient, hypertension in one patient, and constipation and febrile neutropenia in one patient. The combination of VFL 320 mg/m² and gemcitabine 1250 mg/m² was defined as the maximum tolerated dose. The recommended dose was established at the dose of VFL 320 mg/m² combined with gemcitabine 1000 mg/m². Neither VFL nor gemcitabine seemed to be influencing the pharmacokinetics of each other. All patients were evaluable for tumor response. Seven presented a partial response and eight experienced a stable disease., Conclusions: The combination of VFL 320 mg/m² administered on day 1 combined with gemcitabine 1000 mg/m² given on days 1 and 8 every 3 weeks is established as the RD and was shown to be active in these chemonaive NSCLC patients.

Introduction: MAGE-A3 (Melanoma Associated Antigen-A3) is expressed in cancer cells but not in normal tissues except male germ line cells which are devoid of Major Histocompatibility Complex molecules and therefore do not present MAGE-A3 antigens., Background: MAGE-A3 is expressed in 30 to 60% of non-small cell lung cancers but its function is unknown. Its recognition by cytotoxic T lymphocytes implies its presentation on the cell surface by HLA type A1 molecules that are absent from germ cells., Viewpoints: MAGE-A3 represents a good target for active anticancer immunotherapy. Some trials, which used MAGE-A3 and an adjuvant showed a strong antigen-specific T-cell response with, perhaps, an improved survival., Conclusion: This needs to be confirmed as an adjuvent therapy by current phase III randomized controlled trials., (Copyright © 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor that is currently validated for treatment and has shown survival benefit in various cancers, particularly non-small cell lung cancer. However, a very specific toxicity profile has been observed with bevacizumab. This article presents data from the literature concerning hypertension and proteinuria, and provides recommendations for the management of these toxicities.