Future oncology最新文献

Aims: Up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) have relapsed or refractory (R/R) disease after first-line treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, and outcomes are poor after hematopoietic stem cell transplantation failure. CheckMate 436 (NCT02581631) was a phase 1/2 study to evaluate the efficacy and safety of nivolumab, a PD-1/PD-L1 inhibitor, plus brentuximab vedotin (BV) for the treatment of R/R non-Hodgkin lymphoma.

Materials and methods: Adult patients received nivolumab plus BV in 3-week cycles. The primary endpoint was overall response rate (ORR). Here, we report the results from the R/R DLBCL cohort (n = 42).

Results: With a median follow-up of 7.7 months, the ORR was 28.6% (n = 12), and 7.1% (n = 3) of patients achieved a complete response. Median duration of response (95% CI) was 3.6 (1.2-36.5) months. All patients experienced an adverse event (AE), most commonly diarrhea (n = 20, 47.6%). Grade 3/4 and 5 AEs occurred in 24 (57.1%) and 4 (9.5%) patients, respectively. Any-grade treatment-related AEs occurred in 35 (83.3%) patients. No new safety signals were identified.

Conclusions: Overall, the efficacy data from CheckMate 436 do not support the use of nivolumab plus BV for the treatment of R/R DLBCL.

Background: Durvalumab was initially approved for stage III unresectable non-small cell lung cancer (NSCLC) post-concurrent chemoradiation at 10 mg/kg every two weeks, and starting in November 2020, at 1500 mg every four weeks (Q4W). Real-world evidence is limited on durvalumab Q4W dosing utilization and discontinuation, especially in community-based oncology settings.

Methods: In this retrospective cohort, we examined patients with stage III unresectable NSCLC who initiated durvalumab between 3 January 2019 and 12/31/2021, including those who switched to Q4W dosing or received Q4W dosing only, with follow-up until durvalumab discontinuation, health plan disenrollment, death, or study's end.

Results: Of the 102 patients (mean age: 71 years; 46.1% female; 46.1% non-White; 80.4% formerly smoked), 40 switched to Q4W dosing, and 62 received Q4W dosing only. Median duration of treatment (DoT) was 10.0 months overall and 7.5 months for Q4W only. About one-third of patients receiving Q4W dosing completed treatment. Discontinuation occurred in 51.5% of all patients and 65.5% receiving Q4W dosing only. The most common discontinuation reasons were disease progression (17.7%) and pneumonitis (14.7%).

Conclusion: In this diverse community-based cohort, Q4W dosing outcomes, including DoT and completion rate, were comparable to other real-world studies with Q2W dosing and the PACIFIC and PACIFIC-R trials.

Endocrine therapy (ET) resistance is a major concern when treating estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer. A combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and ET is the current first-line standard of care (SOC) for patients with ER+, HER2- advanced breast cancer. Despite the benefits of ET plus a CDK4/6i, disease progression due to endocrine resistance remains a significant challenge. More effective ETs that can overcome resistance are needed to improve clinical outcomes and maintain quality of life by delaying chemotherapy. Palazestrant is a novel oral, complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD) that blocks both transcriptional activation function domains, AF1 and AF2, resulting in complete inhibition of ER-driven transcription, regardless of estrogen receptor 1 (ESR1) mutation status. As monotherapy, palazestrant showed tolerable safety, favorable pharmacokinetics, and antitumor efficacy in heavily pretreated patients during phase I/II studies. OPERA-01 (NCT06016738) is a phase III study designed to evaluate the safety and efficacy of palazestrant monotherapy compared to SOC ET in patients with ER+, HER2- locally advanced or metastatic breast cancer, regardless of ESR1 mutation status, whose disease advanced following treatment with at least one ET in combination with a CDK4/6i.Clinical Trial Registration: Clinicaltrials.gov NCT06016738. Registered 17 August 2023.

The role of perioperative immunotherapy as a chemotherapy-free option for patients with resectable mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colon cancer is evolving, with early-phase neoadjuvant studies reporting favorable long-term outcomes. AZUR-2 is an ongoing global, Phase III, open-label, randomized study evaluating the efficacy of perioperative dostarlimab monotherapy compared with standard of care (SoC) (adjuvant chemotherapy or surveillance) in adult patients with previously untreated, pathologically confirmed, radiologically evaluable T4N0 or Stage III resectable dMMR/MSIH colon adenocarcinoma. Patients will be randomized 2:1 to receive neoadjuvant dostarlimab 500 mg every 3 weeks (4 cycles), followed by surgery, then adjuvant dostarlimab 1000 mg every 6 weeks (6 cycles), or to receive immediate surgery followed by SoC. The primary endpoint is event-free survival assessed by blinded independent central review. The key secondary endpoint is overall survival; additional secondary endpoints include pathological response assessed by residual viable tumor determined by local assessment, safety, and tolerability.Clinical trial registration: NCT05855200 (www.clinicaltrials.gov).

Aims: To investigate the association between primary cancer type and the tissues affected by immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs).

Patients & methods: A retrospective chart review was conducted on 241 patients representing 262 treatment lines involving ICIs at a single institution.

Results: No significant association was found between cancer type and tissue-specific irAEs. irAE incidence was higher with combination PD-1/CTLA-4 inhibitors vs. PD-1 inhibitors alone (61% vs. 46%, p = 0.042). Median time to first irAE was 7.88 months for PD-1 monotherapy versus 2.30 months for combination therapy (log-rank p = 0.00011), a difference of 5.58 months.

Conclusions: Primary cancer type was not significantly associated with tissue-specific irAEs in ICI-treated patients. The 5.58-month difference in median time to irAE onset has important implications for monitoring protocols. Further research is needed to identify factors predicting irAE patterns and severity.

Background: Consolidative thoracic radiotherapy (RT) following chemo-immunotherapy is increasingly used in extensive-stage small cell lung cancer (ES-SCLC). This study investigates the prognostic value of the estimated radiation dose to immune cells (EDRIC) and its determinants in these patients.

Methods: This retrospective study included 173 ES-SCLC patients between 2020 and 2023. EDRIC was calculated as a function of the number of fractions and the average doses to the lungs, heart, and remaining body. Kaplan-Meier and Cox regression analyses were performed to evaluate overall survival (OS) and progression-free survival (PFS).

Results: GTV, PTV, and N stage were positively correlated with EDRIC (r = 0.2577, p = 0.0006; r = 0.3541, p < 0.01; r = 0.2259, p = 0.0028), while lymphocyte nadir was negatively correlated (r = -0.2190, p = 0.0038). Median OS and PFS were longer in the EDRIC ≤4.68 Gy group (OS: 24.9 vs. 17.4 months, p = 0.003; PFS: 12.4 vs. 10.1 months, p = 0.038). Patients in the EDRIC ≤4.68 Gy group had significantly better OS (HR = 0.56, p = 0.003) and PFS (HR = 0.68, p = 0.039). Bone metastasis was associated with worse OS (HR = 1.88, p = 0.002), and liver metastasis with shorter PFS (HR = 2.05, p = 0.001).

Conclusions: EDRIC is an independent predictor of OS and PFS in ES-SCLC. These findings highlight the need to optimize radiation exposure to the immune system in cancer treatment.

Background: Phosphatidylinositol 3-kinase catalytic subunit Alpha (PIK3CA) is closely correlated with colorectal cancer (CRC). However, the role of PIK3CA in colorectal cancer, particularly in non-metastatic disease, remains inconsistent. In this study, the clinicopathological significance of PIK3CA and its common exon mutations in non-mCRC was explored.

Methods: Data from 448 non‑mCRC patients were obtained from The Cancer Genome Atlas (TCGA), and from 655 non‑mCRC patients at our center. Associations of PIK3CA and its common exon mutations with clinicopathological features and overall survival (OS) were analyzed in non‑mCRC.

Results: In the TCGA cohort, the PIK3CA mutation rate was 26.3%, and mutations were associated with tumor site, TNM stage, and regional lymph node metastasis. Exon 9 mutations correlated with tumor site, while exon 20 mutations were linked to tumor site and lymph node metastasis. In our institutional cohort, the mutation rate was 7.8%, with PIK3CA and exon 20 mutations showing correlations with age, tumor site, TNM stage, and lymph node metastasis. However, neither in TCGA nor in our cohort were PIK3CA mutations or common exon mutations associated with overall survival (OS).

Conclusion: PIK3CA mutation is correlated with age, tumor site, TNM stage, and regional lymph node metastasis in non-mCRC. However, PIK3CA and common exon mutations are not associated with OS in patients with non-mCRC.

Background: Cancer-related fatigue (CRF) reduces physical performance and quality of life (QoL). Some authors suggest including moderate-intensity physical exercise to manage CRF; however, the optimal timing to offer rehabilitation remains unclear. The primary aim is to investigate the feasibility of a pulmonary rehabilitation (PR) program, including physical exercise and educational sessions, for lung cancer patients undergoing cancer treatments; secondary objectives are to investigate its effect on CRF, physical performance, and QoL.

Methods: This randomized controlled trial enrolls 40 patients with stage II or III non-small-cell lung cancer undergoing chemotherapy, radiotherapy, or immunotherapy. Patients are randomly assigned to one of two groups: Group A (early-PR) begins PR after enrollment, at the beginning of non-surgical therapies, while Group B (delayed-PR) begins PR for 3 months after enrollment. The PR program consists of two education sessions focused on CRF management and eight supervised exercise sessions, including aerobic, strengthening, stretching, and breathing exercises, combined with home exercises. CRF, QoL, activity level, and endurance are assessed at the baseline (T0) and at 3 and 6 months (T1-T2). One year after T0, survival is assessed along with the CRF, QoL, and activity level (T3). Feasibility will be assessed at 3 and 6 months.Clinical Trial Registration: www.clinicaltrials.gov identifier is NCT06051136.