By adhering to A'Hern's explicitly defined single-stage Phase II design, the statistical analysis was conducted. Based on scholarly publications, the Phase III clinical trial success parameter was fixed at 36 positive outcomes reported in a patient sample of 71.
71 patients were reviewed, with a median age of 64 years, 66.2% male, 85.9% former or current smokers, 90.2% exhibiting an ECOG performance status of 0-1, 83.1% diagnosed with non-squamous non-small cell lung cancer, and 44% expressing PD-L1. read more Observing a median follow-up period of 81 months after treatment onset, the 4-month progression-free survival rate reached 32% (95% confidence interval, 22-44%), representing 23 successful outcomes among the 71 patients studied. Within the initial four months, the OS rate saw a dramatic ascent to 732%, only to moderately decrease to 243% after two years. Median progression-free survival (PFS) was 22 months (95% confidence interval: 15-30 months), and median overall survival (OS) was 79 months (95% confidence interval: 48-114 months). Four months into the study, the response rate for the overall population was 11% (95% confidence interval: 5-21%), while the disease control rate was 32% (95% confidence interval: 22-44%). No indication of a safety signal was observed.
Despite being given metronomically in the second-line treatment, oral vinorelbine-atezolizumab failed to achieve the predefined PFS benchmark. The vinorelbine and atezolizumab combination did not yield any newly reported safety signals.
Second-line treatment with oral metronomic vinorelbine-atezolizumab failed to meet the pre-established progression-free survival benchmark. Further investigation did not uncover any additional safety concerns related to the concurrent administration of vinorelbine and atezolizumab.
Pembrolizumab, administered three-weekly at a fixed dose of 200mg, is the prescribed treatment. This research project focused on evaluating the clinical outcomes and tolerability of a pharmacokinetic (PK)-guided approach to pembrolizumab treatment in advanced non-small cell lung cancer (NSCLC).
The Sun Yat-Sen University Cancer Center served as the site for our prospective, exploratory study, which enrolled patients with advanced non-small cell lung cancer (NSCLC). Eligible patients, who were receiving pembrolizumab at 200mg every three weeks, may have had chemotherapy administered alongside it, for a total of four cycles. Patients who did not exhibit progressive disease (PD) then received pembrolizumab in dosage intervals adjusted to maintain a steady-state plasma concentration (Css) of pembrolizumab, until progressive disease (PD) arose. A concentration of 15g/ml was chosen as the effective concentration (Ce), and new dose intervals (T) for pembrolizumab were calculated via steady-state concentration (Css), following the equation Css21D = Ce (15g/ml)T. The primary focus was on progression-free survival (PFS), and the secondary endpoints encompassed objective response rate (ORR) and safety considerations. Furthermore, advanced NSCLC patients were given pembrolizumab, 200mg every three weeks, and patients completing more than four cycles of treatment at our facility were considered the historical control group. Patients exhibiting Css levels of pembrolizumab were subjected to a genetic polymorphism analysis of the variable number tandem repeats (VNTR) region within their neonatal Fc receptor (FcRn). This study's enrollment was formally documented on ClinicalTrials.gov. Research study NCT05226728.
A total of 33 patients received treatment with pembrolizumab, with dosage intervals adjusted. Css levels of pembrolizumab were observed to range from 1101 to 6121 g/mL. Prolonged intervals (22-80 days) were required by 30 patients; 3 patients had shortened intervals (15-20 days). A median PFS of 151 months and an ORR of 576% were observed in the PK-guided cohort, in stark comparison to the 77-month median PFS and 482% ORR found in the history-controlled cohort. A comparison of the two cohorts revealed 152% and 179% rates of immune-related adverse events. Genotyping FcRn as VNTR3/VNTR3 led to a significantly elevated pembrolizumab Css compared to the VNTR2/VNTR3 genotype (p=0.0005).
The administration of pembrolizumab, with pharmacokinetic guidance (PK), resulted in favorable clinical outcomes and manageable toxicity profiles. The financial burden of pembrolizumab treatment could potentially be mitigated by using a pharmacokinetic-guided, less frequent dosing regimen. This provided a novel, rational therapeutic strategy using pembrolizumab, offering an alternative option for advanced non-small cell lung cancer.
Administration of pembrolizumab, using PK-parameters as a guide, exhibited positive clinical outcomes and controlled adverse effects. Less frequent pembrolizumab dosing, in alignment with pharmacokinetic profiling, may decrease the potential for financial toxicity. read more An alternative, rational therapeutic strategy for advanced NSCLC was presented, utilizing pembrolizumab.
A comprehensive study was undertaken to evaluate the advanced non-small cell lung cancer (NSCLC) patient population, including KRAS G12C prevalence, patient factors, and survival outcomes following the implementation of immunotherapies.
From January 1, 2018, to June 30, 2021, adult patients diagnosed with advanced non-small cell lung cancer (NSCLC) were determined by querying the Danish health registries. Patients were segregated into groups depending on the presence of specific mutations; these groups included those with any KRAS mutation, those with the KRAS G12C mutation, and those who were wild-type for KRAS, EGFR, and ALK (Triple WT). Patient and tumor characteristics, KRAS G12C prevalence, treatment background, time to next treatment, and overall survival metrics were evaluated in our study.
In the group of 7440 patients, 2969 (representing 40%) underwent KRAS testing prior to receiving their first-line therapy. read more Eleven percent (n=328) of the KRAS-tested samples harbored the KRAS G12C genetic variant. The KRAS G12C patient population consisted of 67% women and 86% smokers. A notable 50% demonstrated elevated PD-L1 levels (54%), and these patients were more likely to receive anti-PD-L1 therapy compared to other groups. The observed OS (71-73 months) in both groups mirrored each other precisely from the time of the mutational test result. For the KRAS G12C mutated group, the overall survival (OS) from LOT1 (140 months) and LOT2 (108 months), and time to next treatment (TTNT) from LOT1 (69 months) and LOT2 (63 months), was numerically longer than observed in any other group. Despite variations, OS and TTNT results from LOT1 and LOT2 were similar, when assessed based on PD-L1 expression levels within each group. Patients with high PD-L1 expression demonstrated significantly longer OS, irrespective of their mutational group.
After administering anti-PD-1/L1 therapies to NSCLC patients with advanced disease, survival rates in those with KRAS G12C mutation are equivalent to survival rates in those with other KRAS mutations, those with wild-type KRAS, and all other NSCLC patients.
Following the introduction of anti-PD-1/L1 therapies for advanced non-small cell lung cancer (NSCLC), survival outcomes in KRAS G12C mutation-positive patients are similar to those observed in patients bearing other KRAS mutations, those with wild-type KRAS, and overall NSCLC patient populations.
The antitumor activity of Amivantamab, a fully humanized EGFR-MET bispecific antibody, is observed in a range of EGFR- and MET-driven non-small cell lung cancers (NSCLC), while its safety profile mirrors its expected on-target activity. Amivantamab is frequently associated with reported infusion-related reactions (IRRs). Amivantamab-treated patients are followed to evaluate the internal rate of return and subsequent care adjustments.
The dataset for this analysis comprises patients from the ongoing phase 1 CHRYSALIS study on advanced EGFR-mutated non-small cell lung cancer (NSCLC), who were given intravenous amivantamab at the approved dose of 1050mg (for patients under 80 kg) or 1400mg (for patients weighing 80 kg or more). Splitting the first dose of IRR mitigation (350 mg on day 1 [D1] and the remaining amount on day 2 [D2]) was accompanied by decreased initial infusion rates, proactive infusion interruptions, and the use of steroid premedication before the initial dose. For all infusions, prior administration of antihistamines and antipyretics was a standard procedure. Post-initial dose steroid treatment was left open to patient preference.
By March 30th, 2021, amivantamab had been administered to 380 patients. In 256 patients (67% of the sample), IRRs were noted. Manifestations of IRR encompassed chills, dyspnea, flushing, nausea, chest discomfort, and the experience of vomiting. Within the 279 IRRs assessed, a significant proportion were classified as grade 1 or 2; 7 patients presented with grade 3 IRR, and a single patient displayed a grade 4 IRR. A substantial 90% of all observed IRRs took place during cycle 1, day 1 (C1D1). The median time to the initial IRR onset within C1D1 was 60 minutes. Remarkably, first-infusion IRRs did not interrupt or prevent subsequent infusions. Per protocol, on Cycle 1, Day 1, IRR was managed by stopping the infusion (56%, 214/380), resuming at a lower rate (53%, 202/380), or stopping altogether (14%, 53/380). Completion of C1D2 infusions was achieved in 85% (45 cases) of patients who had their initial C1D1 infusions aborted (53 total). A discontinuation of treatment was observed in four patients (1% or 4 out of 380) as a consequence of IRR. In an effort to pinpoint the underlying mechanism(s) driving IRR, no consistent pattern was found comparing patients with IRR to those without.
Amivantamab's infusion reactions were primarily low-grade and confined to the initial infusion, and reactions were exceptionally uncommon with later infusions. Rigorous monitoring of IRR is critical during and after the initial amivantamab dose, and intervention should be promptly initiated at the first signs of IRR.
The infusion reactions associated with amivantamab were predominantly of a low grade and limited to the first infusion, and were rarely seen with repeated administrations.