Activity of EGFR Tyrosine Kinase Inhibitors in NSCLC With Refractory Leptomeningeal Metastases

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Long-term complete remission with ipilimumab in metastatic castrate-resistant prostate cancer: case report of two patients

Abstract Background Prostate cancer is one of the most common cancers in men and the fourth leading cause of cancer mortality worldwide. Although major progress has been achieved in the last years for patients with metastatic castrate-resistant prostate cancer (mCRPC), thanks to next-generation androgen receptor axis targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been widely approved and used for the treatment of prostate cancer. Two large studies with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody reported improved progression-free survival, but not statistically improved overall survival at the primary analysis (CA184 043 and CA184 095). Case presentation Here, we report on two patients who received ipilimumab in these trials and are still in long-term complete remission with a follow-up of 64 and 52 months respectively after the initiation of ipilimumab. Immunohistochemical staining for hMLH1, hMSH2, hMSH6 and PMS2 was performed on archival prostate biopsy samples from one of the two patients; they exhibited normal protein expression. Interestingly for this patient, a high CD3+ and CD8+ T cell infiltration was observed on archival prostate biopsies as well as Treg FoxP3+ T cells. Conclusion Ipilimumab produces clinical activity in patients with CRPC, including very long responders with no detectable residual disease

Low risk of invasive lobular carcinoma of the breast in carriers of BRCA1 (hereditary breast and ovarian cancer) and TP53 (Li-Fraumeni syndrome) germline mutations

International audienceBACKGROUND:Invasive lobular carcinoma (ILC) of the breast has epidemiological, molecular and clinical specificities, and should likely be considered a unique entity. As for genetic susceptibility, CDH1 germline mutations predispose exclusively to ILC. Data are however scarce regarding ILC in women with BRCA1/2 (Hereditary Breast and Ovarian Cancer) and TP53 (Li-Fraumeni syndrome) germline mutations.METHODS:We included all breast cancers from female patients tested at our institute between 1992 and 2016 (n = 3469) for which pathology data were available. ILC proportion comparison according to mutational status was performed by a chi-squared test. The impact of susceptibility genes on ILC proportion was investigated by univariate logistic regression with wild-type patients as reference.RESULTS AND DISCUSSION:There were 265 (7.64%) ILC: 2/342 (0.58%) in BRCA1 patients, 24/238 (10%) in BRCA2 patients, 1/57 (1.75%) in TP53 patients and 238/2832 (8.4%) in non-carriers. The majority of breast cancers in all groups were invasive ductal and ductal in situ carcinomas. The difference in ILC proportion was highly significant (P < 0.001). Compared to wild-type patients, BRCA1 was associated with a lower ILC proportion (OR 0.064 [95% CI 0.016;0.259], P < 0.0001). BRCA2 OR was 1.222 [95%CI 0.785;1.902] (P = 0.374), TP53 OR was 0.195 [95%CI 0.027;1.412] (P = 0.105). ILC are therefore underrepresented in BRCA1 and TP53 mutation carriers. Formal significance (P = 0.05) was not reached for TP53, but statistical power was only 38%. Based on ILC incidence in the general population, we make the hypothesis that BRCA1 and TP53 do not predispose to ILC, as the few occurrences of ILC in mutation carriers could be attributed to chance and not to germline mutations. Our observations will be useful to clinical cancer geneticists managing patients with ILC, as a BRCA1 or TP53 mutation in these patients would be unlikely. Genetic counseling should be adapted accordingly

Stereotactic body radiotherapy for extra-cranial oligoprogressive or oligorecurrent small-cell lung cancer

Introduction: The role of local ablative treatments, including stereotactic body radiotherapy (SBRT), is an area of active research in oligometastatic patients. Small cell lung cancer (SCLC) has a poor prognosis, with common diffuse metastatic evolution. We evaluated the outcomes after SBRT in uncommon oligoprogressive/oligorecurrent SCLC presentation. Methods: Data of SCLC patients who received SBRT for oligoprogressive/oligorecurrent metastatic disease at four centers were retrospectively analyzed. Patients with synchronous oligometastatic disease, SBRT for primary lung tumor and brain radiosurgery were not included. Relapse and survival rates were defined as the time between the date of SBRT and the first event. Results: Twenty patients (60% with initially limited-disease [LD]) presenting 24 lesions were identified. Oligoprogression and oligorecurrence were observed in 6/20 (30%) and 14/20 (70%) patients, respectively. SBRT was delivered to one (n = 16) to two (n = 4) lesions (median size, 26 mm), mainly to lung [n = 17/24] metastases. At a median follow-up of 2.9 years, no local relapse was observed and 15/20 patients experienced a distant relapse (DR). The median DR and OS were 4.5 months (95 %CI: 2.9–13.7 months) and 17.2 months (95 %CI: 7.5–65.2 months), respectively. The 3-year distant control and OS rates were 25% (95 %CI: 6–44%) and 37% (95 %CI: 15–59%), respectively. Initial LD (vs extensive-disease) was the only prognosis factor associated with a lower risk of post-SBRT DR (HR: 0.3; 95% CI: 0–0.88; p = 0.03). There was no severe observed SBRT-related toxicities. Conclusion: Prognosis was poor, with DR occurring in most patients. However, local control was excellent and long term response after SBRT may rarely occur in patients with oligoprogressive/oligorecurrent SCLC. Local ablative treatments should be discussed in a multidisciplinary setting on well-selected cases

Treatments outcomes in histological variants and non-urothelial bladder cancer: results of a multicenter retrospective study

Introduction: Less than one-third of bladder cancers are non-pure urothelial carcinoma [with variant histological (VH) or non-urothelial carcinoma (non-UC)] for which no treatment guidelines are available. We aim to evaluate the efficacy of systemic treatments in VH or non-UC bladder cancers. Materials: Multicenter retrospective analysis of patients treated for advanced or metastatic VH or non-UC bladder cancers. Primary endpoint was overall response rate (ORR) according to treatment line, regimen and histology subtype. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results: Between 2005 and 2020, 46 patients from seven centers were included. The median age was 66 years (58.75; 74.75), 65.2% were male and 67.2% presented VH. At first line, the ORR for the entire population was 54.4% and median OS was 21.6 months (95% confidence interval [CI]: 14.2-38.6). The ORR of the 37 patients treated with chemotherapy at first line was 62.2% with median PFS and OS of 7.3 (95% CI: 4.5-8.6) and 21.6 months (95% CI: 14.2-35.7), respectively. Dose dense MVAC and platinum doublet chemotherapy had the highest ORR (71.4% and 65.2%). The 9 patients treated with immunotherapy at first line had an ORR of 22.2%, a median PFS of 3.3 months (95% CI:2.3-NR) and the median OS was not reached (95% CI:13.8-NR). Response to treatment varied depending on the histological sub-types and on the treatment type. Conclusion: Chemotherapy and immunotherapy have shown to be effective in VH or non-UC cancers, a rare histological subtype for which we currently have very little data in the literature