A'Hern's precisely defined single-stage Phase II design served as the foundation for the statistical analysis. The Phase III trial's success requirement was derived from the analysis of relevant literature, culminating in a threshold of 36 successes amongst 71 patients.
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. Fer-1 research buy From the commencement of treatment, a median follow-up of 81 months revealed a 4-month progression-free survival rate of 32% (confidence interval 95%, 22-44%), corresponding to 23 favorable outcomes observed in 71 patients. The OS rate was a noteworthy 732% after four months of operation, easing to 243% after two years. Median values for progression-free survival were 22 months (95% CI: 15-30), and for overall survival were 79 months (95% CI: 48-114). The overall response rate at four months was 11% (95% confidence interval: 5-21%), with a 32% (95% confidence interval: 22-44%) disease control rate. No visual or other indication of a safety signal was present.
Metronomic oral vinorelbine-atezolizumab, employed in the second-line setting, fell short of the predetermined PFS threshold. For the vinorelbine-atezolizumab regimen, no new safety alerts were recorded.
The oral metronomic administration of vinorelbine-atezolizumab in the context of second-line therapy did not achieve the predetermined progression-free survival goal. A further review of the clinical data concerning the vinorelbine-atezolizumab combination revealed no new safety signals.
For pembrolizumab therapy, a dosage of 200mg is given every three weeks as the standard protocol. To investigate the clinical efficacy and safety of pembrolizumab administration, guided by pharmacokinetic (PK) data, in patients with advanced non-small cell lung cancer (NSCLC), we undertook this study.
Our prospective, exploratory study at Sun Yat-Sen University Cancer Center involved the enrollment of patients diagnosed with advanced non-small cell lung cancer (NSCLC). Pembrolizumab, at a dose of 200mg every three weeks, was given to eligible patients with or without chemotherapy, for four cycles. In patients without progressive disease (PD), dose intervals were subsequently adjusted to maintain a steady-state plasma concentration (Css) of pembrolizumab, until progressive disease (PD) presented. We established an effective concentration (Ce) of 15g/ml, and calculated new dose intervals (T) based on the steady-state concentration (Css) of pembrolizumab, utilizing the equation Css21D = Ce (15g/ml)T. Concerning the study's metrics, progression-free survival (PFS) was the primary endpoint, while objective response rate (ORR) and safety formed the secondary endpoints. Patients with advanced non-small cell lung cancer (NSCLC) also received pembrolizumab, 200 mg every three weeks, and those who completed over four treatment cycles at our facility were designated as 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). Information regarding this study's participation was recorded on ClinicalTrials.gov. NCT05226728.
33 patients underwent treatment with pembrolizumab, utilizing a newly adapted dosing schedule. Thirty patients required prolonged intervals (22-80 days), while three patients had shortened intervals (15-20 days) for pembrolizumab. The Css levels of pembrolizumab were found to range from 1101 to 6121 g/mL. In the PK-guided cohort, the median progression-free survival was 151 months, and the objective response rate reached 576%; conversely, the history-controlled cohort displayed a 77-month median PFS and a 482% ORR. The two cohorts demonstrated immune-related adverse event rates of 152% and 179%, respectively. The FcRn VNTR3/VNTR3 genotype produced a significantly higher concentration (Css) of pembrolizumab in the bloodstream compared to the VNTR2/VNTR3 genotype (p=0.0005).
Pharmacokinetic (PK)-driven pembrolizumab therapy proved beneficial clinically and associated with manageable toxicity. A reduced dosing frequency of pembrolizumab, tailored by pharmacokinetic data, could potentially mitigate the financial toxicity associated with the treatment. Pembrolizumab's application in advanced non-small cell lung cancer (NSCLC) was presented as a novel, rational, and therapeutic alternative.
Pembrolizumab administration, guided by PK parameters, demonstrated encouraging clinical effectiveness and tolerable adverse effects. Less frequent pembrolizumab dosing, in alignment with pharmacokinetic profiling, may decrease the potential for financial toxicity. Fer-1 research buy An alternative, rational therapeutic strategy for advanced NSCLC was presented, utilizing pembrolizumab.
Our objective was to profile the advanced non-small cell lung cancer (NSCLC) patient cohort, considering the incidence of KRAS G12C, patient attributes, and post-immunotherapy survival outcomes.
The Danish health registries enabled the identification of adult patients diagnosed with advanced non-small cell lung cancer (NSCLC) from January 1, 2018, to June 30, 2021. Patient stratification was performed according to mutational status; groups included individuals with any KRAS mutation, those with the KRAS G12C mutation, and patients displaying wild-type KRAS, EGFR, and ALK (Triple WT). Our study evaluated the prevalence of KRAS G12C, patient and tumor characteristics, medical history of treatment, time to subsequent treatment, and final survival rates.
From the 7440 patients identified, a subgroup of 2969 (40%) had KRAS testing completed before receiving their first-line therapy (LOT1). Fer-1 research buy The KRAS G12C mutation was present in 11% (n=328) of the KRAS samples analyzed. KRAS G12C patients were predominantly female (67%), smokers (86%), and had elevated PD-L1 expression (50% with 54% in particular). Anti-PD-L1 treatment was administered more frequently to this group than any other. The groups exhibited a consistent OS (71-73 months) pattern beginning with the mutational test results' date. 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. Comparing LOT1 and LOT2, the OS and TTNT results showed a consistent pattern across different PD-L1 expression level groups. A substantially longer overall survival (OS) was observed in patients with elevated PD-L1 expression, irrespective of the specific mutational group.
In patients diagnosed with advanced non-small cell lung cancer (NSCLC) and subsequently treated with anti-PD-1/L1 therapies, survival rates in KRAS G12C mutation positive patients are similar to patients with other KRAS mutations, wild-type KRAS, and all NSCLC cases.
In advanced non-small cell lung cancer (NSCLC) patients post-anti-PD-1/L1 therapy, the survival rates of those harboring a KRAS G12C mutation are equivalent to those seen in patients with other KRAS mutations, wild-type KRAS, and all NSCLC patients combined.
Amivantamab, a fully humanized bispecific antibody targeting both EGFR and MET, displays antitumor efficacy across various EGFR- and MET-driven non-small cell lung cancers (NSCLC) and a safety profile aligned with its intended on-target actions. Amivantamab is frequently linked to the occurrence of infusion-related reactions. Patient management strategies, including IRR calculation, are reviewed for those receiving amivantamab treatment.
Patients within the ongoing CHRYSALIS phase 1 trial investigating advanced EGFR-mutated non-small cell lung cancer (NSCLC) and treated with the approved intravenous dose of amivantamab (1050mg for <80kg patients, 1400mg for ≥80kg patients) were part of the current analysis. IRR mitigation strategies involved administering a split first dose (350mg on day 1 [D1]; the remaining portion on day 2 [D2]), lowering initial infusion rates, and incorporating proactive infusion interruptions, along with steroid premedication prior to the initial dose. Antihistamines and antipyretics were necessary for all dosages of the infusion. An initial steroid dose was given, followed by the optional use of steroids.
By March 30th, 2021, amivantamab had been administered to 380 patients. The incidence of IRRs in the patient group was 67%, equivalent to 256 patients. Manifestations of IRR encompassed chills, dyspnea, flushing, nausea, chest discomfort, and the experience of vomiting. In the analysis of 279 IRRs, the predominant grades were 1 or 2; 7 patients exhibited grade 3 IRR, and 1 patient presented with grade 4 IRR. During cycle 1, day 1 (C1D1), 90% of all observed IRRs arose. The median time elapsed before the first IRR appeared on C1D1 was 60 minutes; notably, first-infusion IRRs did not compromise subsequent infusions. The protocol dictated that IRR was controlled on the first day of the first cycle by suspending the infusion in 56% of cases (214 out of 380), reducing the infusion rate in 53% (202/380) of cases, and stopping the infusion in 14% (53 out of 380) of instances. C1D2 infusions were completed in a substantial 85% (45 out of 53) of patients whose C1D1 infusions were aborted. IRR led to the cessation of treatment in four patients (representing 1% of the 380 patients). In an effort to pinpoint the underlying mechanism(s) driving IRR, no consistent pattern was found comparing patients with IRR to those without.
The majority of amivantamab-induced infusion reactions were of a low severity and confined to the first infusion, and subsequent doses were exceptionally unlikely to cause them. The administration of amivantamab should include routine monitoring for IRR following the initial dosage, with immediate intervention upon the earliest appearance of IRR symptoms.
Low-grade infusion-related reactions to amivantamab were mostly limited to the first dose, with subsequent doses rarely inducing any.