Twelve-month Overall Survival Research Articles

Lurbinectedin in small cell lung cancer: real-world experience of a multicentre national early access programme.

Lurbinectedin is a novel oncogenic transcription inhibitor active in several cancers, including small cell lung cancer (SCLC). We aimed to describe the first Australian experience of the clinical efficacy and tolerability of lurbinectedin for the treatment of SCLC after progression on platinum-containing therapy. Multicentre real-world study of individuals with SCLC initiating lurbinectedin monotherapy (3.2 mg/m2 three-weekly) on an early access programme between May 2020 and December 2021. Key outcomes were clinical utilisation, efficacy and tolerability. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Outcome data were collected within the AUstralian Registry and biObank of thoRacic cAncers (AURORA). Data were analysed for 46 individuals across seven sites. Lurbinectedin was given as second- (83%, 38/46) or subsequent- (17%, 8/46) line therapy, mostly with prior chemoimmunotherapy (87%, 40/46). We report dose modifications (17%, 8/46), interruptions/delays (24%, 11/46), high-grade toxicities (28%, 13/46) and hospitalisations (54%, 25/46) during active treatment. The overall response rate was 33% and the disease control rate was 50%. Six-month OS was 44% (95% confidence interval (CI): 29.0-57.1). Twelve-month OS was 15% (95% CI: 6.5-26.8). From lurbinectedin first dose, the median PFS was 2.5 months (95% CI: 1.8-2.9) and OS was 4.5 months (95% CI: 3.5-7.2). From SCLC diagnosis, the median OS was 12.9 months (95% CI: 11.0-17.2). Individuals with a longer chemotherapy-free interval prior to lurbinectedin had longer PFS and OS. This real-world national experience of lurbinectedin post-platinum chemotherapy and immunotherapy for individuals with SCLC was similar to that reported in clinical trials.

Association of pretreatment CA19-9 with survival after 3-fraction SBRT for locally advanced pancreatic cancer: Results from a phase I dose-escalation trial.

613 Background: The optimal dose and fractionation scheme for stereotactic body radiotherapy (SBRT) is unknown. The biologic effects of ultra-high doses per fraction (>8Gy) are theoretical, but may include eliciting an effect on the endothelial cells of the tumor vasculature which could improve treatment response. This study aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for locally advanced pancreatic cancer (LAPC). Methods: A multi-site phase 1 dose escalation trial was conducted from March 2016 to April 2019 at Memorial Sloan Kettering Cancer Center (NCT02643498) and University of Colorado (NCT02873598). Patients with localized histologically confirmed pancreatic adenocarcinoma deemed unresectable on multidisciplinary review without distant progression following induction chemotherapy for ≥ 2 months were eligible. Patients received 3-fraction LINAC-based SBRT at 3 dose levels, 27Gy, 30Gy and 33Gy following a modified 3+3 design, allowing for enrollment of additional patients at the last dose level during the 90-day observation period, provided no dose-limiting toxicities (DLTs) were observed. DLTs were defined as ≥ Grade 3 treatment-related GI toxicity within 90 days of RT by CTCAE v.4. The secondary endpoints were overall survival (OS), local progression-free and distant metastasis-free survival (LPFS and DMFS, respectively). Univariate analysis using log-rank test was performed to identify factors associated with OS. Results: Twenty-three evaluable patients were enrolled, including 8 patients at 27Gy, 8 patients at 30Gy and 7 patients at 33Gy. The median age was 67 years (range 52 - 79), 9 patients (39%) were male, all were stage IIIwith a median tumor size of 3.5cm (range, 1.0 - 6.4) and CA19-9 of 60U/mL (range, <1 - 4880). All received chemotherapy for a median of 4.0 months (range 2.5 -11.4). There were no grade ≥ 3 abdominal pain, dyspepsia, diarrhea, nausea, vomiting, or gastrointestinal hemorrhage. Four patients underwent resections (pancreaticoduodenectomy=3, Appleby=1). Twelve-month rates of OS, DMFS and LPFS were 45.8 %, 37.7% and 53.0%, respectively. On univariate analysis, CA19-9 (HR=0.2365, 95%CI 0.07999 to 0.6990), but not dose level, size, N stage, tumor location, duration of chemotherapy were associated with OS. Twelve-month OS for patients with CA19-9 ≤ 60U/mL vs > 60U/mL were 80% vs 27% (p=0.0023). Conclusions: For select LAPC patients, dose escalation to the target dose of 33Gy in 3 fractions resulted in no DLTs and disease outcomes comparable to conventional RT. Lower pre-SBRT CA19-9 values were associated with improved OS and could help identify patients most likely to benefit from local therapies. Continued exploration of (ultra)hypofractionated schemes to maximize tumor control while enabling efficient integration of RT with systemic therapy is warranted. Clinical trial information: NCT02643498/NCT02873598.

Outcomes and Toxicities of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real-World, Multicenter Retrospective Analysis.

Although classical Hodgkin lymphoma (cHL) is highly curable, 20%-30% of patients will not be cured with conventional treatments. The programmed death-1 (PD-1) inhibitors (PD-1i) nivolumab and pembrolizumab have been Food and Drug Administration-approved for relapsed/refractory (R/R) cHL. There is limited data on the real-world experience with PD-1i in cHL and it is unknown whether fewer selected patients treated with PD-1i derive benefits similar to those observed in published trials. We performed a multicenter, retrospective analysis of R/R cHL patients treated with PD-1i in the nontrial setting. The primary objective was to describe progression-free survival (PFS) and overall survival (OS) in this population. Secondary objectives were to characterize response rates, toxicities, discontinuation patterns, and post-PD-1i therapies. The study included 53 patients from nine U.S. centers. Overall response rate (ORR), complete response (CR), and partial response (PR) to PD-1i were 68%, 45%, and 23%, respectively. Twelve-month OS and PFS were 89% and 75%, respectively; median PFS was 29 months. Ninety-six percent of patients with CR continue to respond at a median follow-up of 20 months. Toxicities were similar to those previously described. Seventy percent of patients treated with systemic therapy after PD-1i demonstrated objective responses. To our knowledge, this analysis is the first describing real-world experience with PD-1i in cHL patients in the U.S. Here, we demonstrate similar response rates compared to prior studies. The toxicity profile of PD-1i was similar to that seen in previous studies; we further describe toxicity patterns in those with prior autoimmune disease or allogeneic transplant. Post-PD-1i systemic therapies appear active. These results support the effectiveness and tolerability of PD-1i therapy in R/R cHL in a real-world setting. Two PD-1 inhibitors have recently been approved for patients with relapsed/refractory classical Hodgkin lymphoma based on results from nonrandomized clinical trials. However, to date, there have been no studies evaluating the effectiveness and toxicity profile of these drugs in the real-world setting in the U.S. The present study demonstrates that patients treated in a real-world context experience similar rates of overall effectiveness compared with published clinical trials. Patients who discontinue PD-1 inhibitors may experience clinical responses to subsequent treatment with systemic chemotherapy or targeted therapy. This study provides clinicians with further insight into the effectiveness and tolerability of PD-1 inhibitors and suggests that when patients progress while on these drugs, conventional systemic chemotherapy may be an effective treatment option.

Is there a role for high dose chemotherapy with hematopoietic stem cell rescue in patients with relapsed supratentorial PNET?

Supratentorial primitive neuroectodermal tumors (sPNET) are rare childhood brain tumors. There is no standard strategy for treating relapsed sPNETs. The role of high dose chemotherapy with hematopoietic stem cell rescue (HDC with HSCR) in treating relapsed sPNET is controversial. A systematic review of the literature regarding outcome of patients with relapsed sPNET treated with HDC and HSCR was performed to examine the potential predictive factors that would justify its use in this subset of patients. Forty-six patients were identified fulfilling the inclusion criteria. Of those, 15 patients were infants and 15 were pineoblastomas. With a median follow-up of 40 months (range 3-123 months) 15 patients were reported alive. Thirteen patients out of the 15 survivors did not receive craniospinal irradiation (CSRT). The 12 month overall survival (OS) of the cohort was 44.2 ± 7.5 months. Twelve-month OS for children less than 36 months was 66.7 ± 12.2 months while for older children it was 27.8 ± 10.6 (P = 0.003). Twelve-month OS was 20.0 ± 10.3 for those patients with pineoblastoma versus 54.6 ± 9.0 for those with non-pineal sPNETs (P < 0.001). Cox regression analysis revealed pineal location as the only independent adverse prognostic factor. In conclusion high dose chemotherapy with HSCR might lead to survival primarily in younger children with relapsed sPNET even in the absence of concomitant use of radiotherapy, whereas the outcome in older children and/or in pineal location is extremely poor with this modality.