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Background: Immune-checkpoint inhibitors (ICIs) have significantly improved outcome of advanced non-small cell lung cancer (aNSCLC) patients. However, their efficacy remains uncertain in uncommon histologies (UH)., Materials and Methods: Data from ICI treated aNSCLC patients (April,2013-January,2021) in one Institution were retrospectively collected. Univariate and multivariate survival analyses were estimated by Kaplan-Meier and Cox proportional hazards regression model, respectively. Objective response rate (ORR) and disease control rate (DCR) were assessed., Results: Of 375 patients, 79 (21.1%) had UH: 19 (24.1%) sarcomatoid carcinoma, 15 (19.0%) mucinous adenocarcinoma, 10 (12.6%) enteric adenocarcinoma, 8 (10.1%) adenocarcinoma not otherwise specified, 7 (8.9%) large-cell neuroendocrine carcinoma, 6 (7.6%) mixed histology non-adenosquamous, 5 (6.3%) adenosquamous carcinoma, 9 (11.4%) other UH. In UH group, programmed death-ligand 1 (PD-L1) <1%, 1-49%, ≥50% and unknown expression were reported in 27.8%, 22.8%, 31.7% and 17.7% patients respectively and ICI was the second/further-line in the majority of patients. After a median follow-up of 35.64 months (m), median progression-free survival (mPFS) was 2.5 m in UH [95% CI 2.2-2.9 m] versus (vs.) 2.7 m in CH [95% CI 2.3-3.2 m, P-value = .584]; median overall survival (mOS) was 8.8 m [95% CI 4.9-12.6 m] vs. 9.7 m [95% CI 8.0-11.3 m, P-value = .653]. At multivariate analyses only ECOG PS was a confirmed prognostic factor in UH. ORR and DCR were 25.3% and 40.5% in UH vs. 21.6% and 49.5% in CH [P-value = .493 and .155 respectively]., Conclusions: No significant differences were detected between UH and CH groups. Prospective trials are needed to understand ICIs role in UH population., (Copyright © 2021. Published by Elsevier Inc.)

Patients with solid tumors and mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) are eligible for immunotherapy. Recently, different reports described patients with poor performance status (PS), unrelated to comorbidities, which showed a rapid improvement of their clinical conditions under immunotherapy, which evoked a Lazarus response. Very few data on the efficacy and safety of immunotherapy in patients with gynecological malignancies and poor PS are available. Based on the GARNET trial, Dostarlimab, a monoclonal antibody anti-programmed death receptor-1 (PD-1), has been approved in advanced or recurrent mismatch repair deficient endometrial cancer (EC) which progressed after platinum-based therapy. For the first time, in gynecological oncology, an immune checkpoint inhibitor drastically changed the clinical practice. We collected a multicenter case series of six patients with advanced endometrial carcinoma and PS ECOG 3–4 treated with Dostarlimab, showing exceptionally quick responses and significant improvement of PS to configure a Lazarus response. [ABSTRACT FROM AUTHOR]

• Impact of bone tumor burden on survival upon bone targeted agents in aNSCLC pts treated with ICI is still unknown. • Our findings highlight a survival benefit in aNSCLC pts with HBTB treated with concomitant ICI and BTA, especially denosumab. • HBTB should be included as a stratification factor in future trials assessing BTA and ICI combinations inaNSCLC pts with BM. Bone-targeted agents (BTA), such as denosumab (DN) and zoledronic acid (ZA), have historically reduced the risk of skeletal related events in cancer patients with bone metastases (BM), with no improvement in survival outcomes. In the immunotherapy era, BM have been associated with poor prognosis upon immune-checkpoint inhibitors (ICI). Currently, the impact of bone tumor burden on survival upon BTAs in advanced non-small cell lung cancer (aNSCLC) patients treated with ICI remains unknown. Data from ICI-treated aNSCLC patients with BM (4/2013-5/2022) in one institution were retrospectively collected. BTA-ICI concurrent treatment was defined as BTA administration at any time before or within 90 days from ICI start. High bone tumor burden (HBTB) was defined as ≥ 3 sites of BM. Median OS (mOS) was estimated with Kaplan-Meier. Aikaike's information criterion (AIC) was used to select the best model for data analysis adjusted for clinical variables. Of 134 patients included, 51 (38 %) received BTA. At a mFU of 39.6 months (m), BTA-ICIs concurrent treatment did not significantly impact on mOS [8.3 m (95% CI 3.9–12.8) versus (vs) 6.8 m (95% CI 4.0–9.6) p = 0.36]; these results were confirmed after adjustment for clinical variables selected by AIC. A multivariate model showed a significant interaction between BTA use and HBTB or radiation therapy to BM. In subgroup analyses, only HBTB confirmed to be associated with significantly longer mOS [8.3 m (95% CI 2.4–14.2) vs 3.5 m (95% CI 2.9–4.1), p = 0.003] and mPFS [3.0 m (95% CI 1.6–4.4) vs 1.8 m (95% CI 1.6–2.0) p = 0.001] upon BTA-ICI concurrent treatment, with the most pronounced OS benefit observed for DN-ICI concurrent regimen [15.2 m (95% CI 0.1–30.7) vs 3.5 m (95% CI 2.9–4.1) p = 0.002]. In the immunotherapy era, HBTB can identify patients experiencing survival benefit with BTA, especially with DN-ICI combination. HBTB should be included as a stratification factor in the upcoming trials assessing BTA and ICI combinations in patients with aNSCLC and BM. [ABSTRACT FROM AUTHOR]

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1 , MYC, PPP2R1A , PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease. • Uterine serous carcinoma (USC) is a rare and aggressive variant of endometrial cancer. • USCs are generally mismatch repair proficient and have extensive copy number alterations. • Multi-modal treatment including surgery, chemotherapy and/or radiotherapy should be considered in the majority patient with USC. • Novel combinations of immune checkpoint inhibitors with targeted therapies are under evaluation. [ABSTRACT FROM AUTHOR]