The Treatment of Advanced Thyroid Cancer Using Pemetrexed Monotherapy or with Platinum-Based Chemotherapy

Paclitaxel and carboplatin after disease progression on immune checkpoint inhibitor for patients with metastatic urothelial carcinoma

Aim: Despite advances with immune checkpoint inhibitor (ICI)-based regimens in the past decade, patients with metastatic urothelial cancer (mUC) face a poor prognosis with few approved options. Platinum-based chemotherapy with paclitaxel and carboplatin (TC) +/– ICI may be a feasible choice. Methods: We generated an IRB-approved, HIPAA-compliant retrospective database of patients at Mayo Clinic Cancer Center with mUC who started TC +/– ICI after disease progression on ICI from January 2018 through December 2024. Baseline demographics, clinicopathologic features, and treatment outcomes were extracted from the electronic health record. Kaplan-Meier method was used to calculate median duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: There were 32 patients who fit inclusion criteria, including 31 patients who had disease progression on ICI in the metastatic setting and 1 patient who developed metastatic disease on adjuvant nivolumab. Patients received a median of 4 cycles (range 1–14) of TC over median 12 weeks (range 3–53). Overall, 81% of patients received TC concurrently with an ICI, and 28% continued maintenance ICI after TC discontinuation (at the treating oncologist’s discretion due to adequate response or toxicity). The best objective response rate was 41% and disease control rate was 75%, with median DOR of 4.8 months (IQR 2.7–10.4), median PFS of 4.6 months (IQR 3.3–10.2), and median OS of 9.4 months (IQR 6.3–15.9). Some patients in this series had very durable responses with PFS > 12 months and OS > 24 months. TC +/– ICI was overall well tolerated with expected type and severity of adverse events. Conclusions: Strategies to overcome ICI resistance are needed, and TC +/– ICI after disease progression on an ICI shows promising tolerability and efficacy in this setting for patients with mUC. Our series was notable for some patients having a durable response. Validation in larger cohorts is warranted.

Effectiveness of first-line therapy for metastatic small-cell lung cancer: real-world data

Background. Small cell lung cancer (SCLC) accounts for about 15% of all lung cancer cases. It is characterized by aggressive progression, high proliferative capacity, and early hematogenous and lymphogenous dissemination. Although there is a significant baseline sensitivity to first-line chemotherapy, the majority of patients experience disease progression within 6 to 12 months following treatment initiation, with a median overall survival of approximately 12 months. Aim. To evaluate the efficacy and safety of first-line therapy utilizing atezolizumab combined with carboplatin or cisplatin and etoposide in patients diagnosed with SCLC in a real-world context. Materials and methods. This retrospective and prospective observational study included 157 patients (119 males and 38 females) aged 32 to 84 years. Compromised performance status (ECOG 2–3) at baseline was observed in 54 patients (34.4%). Results. The median progression-free survival in patients with SCLC undergoing first-line therapy was 6.18 months (95% confidence interval [CI] 5.69-6.90), while the median overall survival was 10.55 months (95% CI 8.12-13.02). An objective response was recorded in 82 patients (52.3%). Grade 3–4 immune-related adverse events were documented in only 5.1% of the patient population. Conclusion. The combination of atezolizumab with platinum-based chemotherapy and etoposide as a first-line treatment for SCLC demonstrates high efficacy and an acceptable safety profile in real-world clinical settings.

Efficacy and Safety of Reduced-Dose Chemotherapy Plus Nivolumab in Elderly Advanced Gastric Cancer

Background/Objective: The standard first-line treatment for advanced or recurrent gastric cancer (AGC) includes chemotherapy combined with an immune checkpoint inhibitor or zolbetuximab, but delivering fluoropyrimidine-platinum chemotherapy at standard doses can be difficult in elderly patients. Method: We retrospectively collected clinical data from 70 patients aged 70 years or older with AGC who received first-line chemotherapy plus nivolumab between July 2017 and December 2024. Patients who started treatment without dose reduction were classified as the normal group, whereas those who received a reduced starting dose of fluoropyrimidine and/or platinum were classified as the reduced group. Results: Fifty patients were assigned to the reduced group and 20 to the normal group. The reduced group was older, more frequently received SOX, and more often had PD-L1 combined positive scores ≥ 1. Objective response rate, disease control rate, progression-free survival, and overall survival did not differ significantly between the groups. In contrast, grade ≥ 3 adverse events and any-grade infections were more frequent in the normal group. Conclusions: These findings suggest that reduced-dose chemotherapy plus nivolumab may be an effective and less toxic first-line option for elderly patients with AGC.

The mDCF combination as first-line therapy in patients with locally advanced or metastatic esophageal squamous cell carcinoma

Introduction. There is no consensus regarding the optimal first-line chemotherapy regimen for locally advanced or metastatic esophageal squamous cell carcinoma. The efficacy of standard chemotherapy combinations is limited and therefore has to be improved. Due to the limited accessibility of modern immunotherapy, chemotherapy remains a valuable commonly used option. We conducted a non-randomized prospective study to evaluate the efficacy and tolerability of the triple combination mDCF. Materials and Methods. The main inclusion criteria of the study were locally advanced or metastatic esophageal squamous cell carcinoma, age over 18 years, patients with an ECOG performance status of ≤ 2 (ECOG, Eastern Cooperative Oncology Group), and satisfactory blood test results. The primary endpoint of the study was the objective response rate (ORR); secondary endpoints included overall survival (OS) and progression-free survival (PFS). Patients received eight cycles of mDCF chemotherapy: docetaxel 40 mg / m2 on day 1, cisplatin 40 mg / m2 on day 1, calcium folinate 400 mg / m2 also on day 1, fluorouracil 400 mg / m2 by intravenous bolus on day 1, followed by a 48-hour infusion of fluorouracil 2000 mg / m2 (1000 mg / m2 daily) on days 1–2. This treatment regimen was administered every 2 weeks. Results. From 2019 to 2025, 74 patients participated in the study. The median age was 62 years; 55 patients (74.3 %) were male and 19 (25.7 %) were female. The tumor was located in the upper third of the esophagus in 9 cases (12 %), the middle third in 31 cases (42 %), and the lower third in 34 cases (46 %). The ECOG performance status was 0 in 11 patients (14.9 %), 1 in 38 patients (51.3 %), and 2 in 25 subjects (33.8 %). The median OS was 13.6 months (95 % CI 10.6-NR), the median PFS was 9.7 months (95 % CI 7.1–22.0), the ORR was 55.4 % (95 % CI 44.1–66.2), and the disease control rate was 78.1 % (95 % CI 67.8–86.0). The most common grade 3–4 adverse events (AEs) during the study were leukopenia (11 cases, 14.8 %), neutropenia (12 cases, 16.2 %), anemia (10 cases, 13.5 %), and thrombocytopenia (15 cases, 20.2 %). There were no treatment-related deaths. Conclusions. The modified 2-week mDCF chemotherapy regimen demonstrated significant improvements in ORR, OS, and PFS, as well as manageable toxicity as a first-line treatment for esophageal squamous cell carcinoma.

[Efficacy of maintenance therapy with or without pembrolizumab in patients with advanced gastric cancer after first-line chemotherapy].

Immunotherapy with Pembrolizumab beyond Progression and Local Ablative Therapy in Oligoprogressive metastatic NSCLC.