Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Lung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. PATIENTS AND METHODS: This retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC. RESULTS: Among the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min-max: 7-173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27-0.58). CONCLUSION: Treatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.

Metastatic inflammatory breast cancer: survival outcomes and prognostic factors in the national, multicentric, and real-life French cohort (ESME).

BACKGROUND: Primary inflammatory breast cancer (IBC) is a rare and aggressive entity whose prognosis has been improved by multimodal therapy. However, 5-year overall survival (OS) remains poor. Given its low incidence, the prognosis of IBC at metastatic stage is poorly described. MATERIALS AND METHODS: This study aimed to compare OS calculated from the diagnosis of metastatic disease between IBC patients and non-IBC patients in the Epidemiological Strategy and Medical Economics database (N = 16 702 patients). Secondary objectives included progression-free survival (PFS) after first-line metastatic treatment, identification of prognostic factors for OS and PFS, and evolution of survival during the study period. RESULTS: From 2008 to 2014, 7465 patients with metastatic breast cancer and known clinical status of their primary tumor (T) were identified (582 IBC and 6883 non-IBC). Compared with metastatic non-IBC, metastatic IBC was associated with less hormone receptor-positive (44% versus 65.6%), more human epidermal growth factor receptor 2-positive (30% versus 18.6%), and more triple-negative (25.9% versus 15.8%) cases, more frequent de novo M1 stage (53.3% versus 27.7%; P < 0.001), and shorter median disease-free interval (2.02 years versus 4.9 years; P < 0.001). With a median follow-up of 50.2 months, median OS was 28.4 months [95% confidence interval (CI) 24.1-33.8 months] versus 37.2 months (95% CI 36.1-38.5 months) in metastatic IBC and non-IBC cases, respectively (P < 0.0001, log-rank test). By multivariate analysis, OS was significantly shorter in the metastatic IBC group compared with the metastatic non-IBC group [hazard ratio = 1.27 (95% CI 1.1-1.4); P = 0.0001]. Survival of metastatic IBC patients improved over the study period: median OS was 24 months (95% CI 20-31.9 months), 29 months (95% CI 21.7-39.9 months), and 36 months (95% CI 27.9-not estimable months) if diagnosis of metastatic disease was carried out until 2010, between 2011 and 2012, and from 2013, respectively (P = 0.003). CONCLUSION: IBC is independently associated with adverse outcome when compared with non-IBC in the metastatic setting.

Endocrine therapy or chemotherapy as first-line therapy in hormone receptor-positive HER2-negative metastatic breast cancer patients.

BACKGROUND: For hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2-) negative metastatic breast cancer (MBC), international guidelines recommend endocrine therapy as first-line treatment, except in case of 'visceral crisis'. In the latter case, chemotherapy is preferred. Few studies have compared these two strategies. We used the Epidemiological Strategy and Medical Economics (ESME) programme, UNICANCER, a large national observational database (NCT03275311), to address this question. METHODS: All patients who initiated treatment for a newly diagnosed HR+ HER2-negative MBC between January 2008 and December 2014 in any of the 18 French Comprehensive Cancer Centers participating to ESME were selected. Patients should be aromatase inhibitor (AI)-sensitive (no previous AI or relapse occurring more than 1 year after last adjuvant AI). Objectives of the study were evaluation of progression-free and overall survival (OS) according to the type of first-line treatment adjusted on main prognostic factors using a propensity score. RESULTS: Six thousand two hundred sixty-five patients were selected: 2733 (43.6%) received endocrine therapy alone, while 3532 (56.4%) received chemotherapy as first-line therapy. Among the latter, 2073 (58.7%) received maintenance endocrine therapy. Median OS was 60.78 months (95% confidence interval [CI], 57.16-64.09) and 49.64 months (95% CI, 47.31-51.64; p < 0.0001) for patients receiving endocrine therapy alone and chemotherapy ± maintenance endocrine therapy, respectively. However, this difference was not significant after adjusting on the propensity score (hazard ratio: 0.943, 95% CI 0.863-1.030, p = 0.19). CONCLUSION: In this large retrospective cohort of patients with AI-sensitive metastatic luminal BC, OS was similar, whether first-line treatment was chemotherapy or endocrine therapy. In agreement with international guidelines, endocrine therapy should be the first choice for first-line systemic treatment for MBC in the absence of visceral crisis.