Summary
Objective
. The clinical outcomes of poor performance status (PS) patients with
epidermal growth factor receptor
(
EGFR
)-mutated non-small cell lung cancer (NSCLC) who are treated with ...osimertinib as a first-line treatment have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in chemotherapy-naive and poor PS (2 or more) patients with NSCLC harboring sensitive
EGFR
mutations.
Materials and Methods.
We assessed the clinical effects of osimertinib as a first-line treatment for patients with poor PS NSCLC with an exon 19 deletion or exon 21 L858R mutation in
EGFR
. All patients were administered osimertinib (80 mg/day) as the initial treatment.
Results.
Sixteen patients (nine women and seven men) who were treated between August 2018 and July 2021 were included in this study; their median age was 78 years. The overall objective response rate was 56.3%. The median progression-free survival (PFS) of the entire patient population was 10.5 months and the PS score improved in 8 of 16 patients (50%). The most common adverse event was acneiform rash (42%), followed by diarrhea (36%) and paronychia (36%); none of these were of grade ≥ 3. Interstitial lung disease occurred in 2 patients (12.5%); however, no treatment-related deaths occurred.
Conclusion.
Considering the findings of this study, osimertinib appears to be an effective and safe treatment option for patients with poor PS and advanced NSCLC harboring sensitive
EGFR
mutations. To obtain conclusive results, further studies with larger cohorts are warranted.
Full text
Available for:
CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Background
Exon 19 deletion and L858R point mutation in exon 21 of the epidermal growth factor receptor (
EGFR
) are the most commonly encountered mutations in patients with non-small cell ...lung cancer (NSCLC) and predict better clinical outcomes following treatment with EGFR-tyrosine kinase inhibitors (TKIs). The inflammatory indicator neutrophil-to-lymphocyte ratio (NLR) in peripheral blood serves as a predictive factor for NSCLC patients treated with chemotherapy. Here, we aimed to evaluate the correlation between NLR and clinical efficacy of EGFR-TKIs in NSCLC patients harboring
EGFR
mutations.
Methods
We retrospectively collected information of 205 patients with advanced NSCLC harboring exon 19 deletion or L858R point mutation and receiving gefitinib or erlotinib. The clinical outcomes in the NSCLC patients were evaluated based on NLR level before EGFR-TKI therapy.
Results
The optimal cut-off value for NLR was 3.55. The response rates in the low-NLR and high-NLR groups were 69.2% and 51.5%, respectively. The median progression-free survival (PFS) in the low-NLR and high-NLR groups were 15.7 months and 6.7 months, respectively. The median overall survival (OS) in the low-NLR and high-NLR groups were 37.6 months and 19.2 months, respectively. The multivariate analysis identified performance status (PS), NLR, stage, and smoking status as independent predictors of PFS. Moreover, the PS and NLR were identified as independent predictors of OS.
Conclusions
NLR was a significant predictor of clinical efficacy and OS in NSCLC patients harboring
EGFR
mutations treated with gefitinib or erlotinib.
Summary
Introduction
Afatinib is used to treat patients with advanced non-small cell lung cancer (NSCLC) harboring common
EGFR
mutations; however, the clinicopathological factors that predict this ...drug’s effectiveness in real-world settings remain unclear. We therefore evaluated the effectiveness of afatinib in such patients and assessed potential prognostic factors.
Methods
We retrospectively investigated patients with NSCLC who received first-line afatinib between July 2014 and August 2018. Variables (including sex, age, performance status, neutrophil-to-lymphocyte ratio,
EGFR
genotype, smoking status, clinical stage prior to treatment stage IV vs.. postoperative recurrence, presence or absence of brain metastases, body surface area, any afatinib dose reductions, and afatinib starting dose 40 vs.. 20 or 30 mg) were subjected to a Cox proportional hazards regression model to estimate progression-free survival (PFS).
Results
Forty-eight patients with a median age of 67 years were included; the objective response rate was 62.5% (30 patients). The median PFS was 14.1 months; the PFS periods were 11.8 and 15.9 months for patients receiving 40 mg versus 20–30 mg of afatinib (
P
= 0.41), respectively, and were 14.5 and 13.8 months for patients who required afatinib dose reduction and those who did not, respectively (
P
= 0.80). The PFS tended to be longer in patients without brain metastases (albeit not significantly). Ultimately, no significant predictive values for PFS were identified.
Conclusions
Afatinib is effective for patients with NSCLC harboring common
EGFR
mutations irrespective of their clinicopathological backgrounds. A direct comparison of afatinib and osimertinib in treatment-naïve patients is warranted to determine the optimal standard of care.
Background
Osimertinib is recommended for non‐small cell lung cancer (NSCLC) patients with EGFR mutation; however, it is unclear whether body size variables affect the efficacy of osimertinib in such ...patients. This study assessed the potential effect of body surface area (BSA) and body mass index (BMI) on osimertinib chemotherapy in patients with T790M‐positive advanced NSCLC who progress on prior EGFR‐tyrosine kinase inhibitors (TKIs).
Methods
We conducted a prospective observational cohort study. Median BSA and BMI were used as cut‐off values to evaluate the impact of body size variables on osimertinib chemotherapy.
Results
The median BSA and BMI of 47 patients were 1.50 m2 and 21.5 kg/m2, respectively. Clinical outcomes did not significantly differ between the high and low BSA groups, with response rates of 59.1% and 56.0% (P = 0.83) and progression‐free survival (PFS) of 7.6 and 9.1 months (P = 0.69), respectively. Similarly, there were no significant differences between the high and low BMI groups relative to response rates, which were 60.8% and 54.1% (P = 0.64), respectively, and PFS, which was 7.6 months in both groups (P = 0.38). No significant differences were observed among toxicity profiles in relation to BSA or BMI. Multivariate analysis identified better performance status, young age, and EGFR exon 19 deletion as independent favorable predictors of PFS.
Conclusion
The efficacy of osimertinib does not significantly vary relative to body size variables of patients with T790M‐positive NSCLC who progress on prior EGFR‐TKIs.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The clinical outcomes of elderly patients with
-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib have not been sufficiently evaluated. This study aimed to assess the ...efficacy and safety of osimertinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive
mutations.
We assessed the clinical effects of osimertinib as a first-line treatment for elderly NSCLC patients (≥75 years of age) with an exon 19 deletion or exon 21 L858R mutation in
. All patients were administered 80 mg/day osimertinib as initial treatment.
Forty-three patients (24 women and 19 men) with adenocarcinoma who were treated between August 2018 and July 2021 were included in this study; their median age was 79 years (range, 75-90 years). The overall objective response rate was 60.5%. The median progression-free survival (PFS) and time to treatment failure (TTF) of the entire patient population were 22.1 months and 14.6 months, respectively. The most common adverse event was rash acneiform (42%), followed by diarrhea (33%) and paronychia (28%); none of these were grades ≥3. Interstitial lung disease developed in 8 patients (18.6%); however, no treatment-related deaths occurred. Multivariate analysis identified performance status and disease stage as predictors of PFS and TTF.
Considering the findings of this study and despite an observed discordance between PFS and TTF, osimertinib appears to be an effective and safe treatment option in elderly patients with advanced NSCLC harboring sensitive
mutations. To obtain conclusive results, further studies in a larger elderly population are warranted.
A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung ...cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of activating
mutation, ie, exon 19 deletion or L858R point mutation.
A prospective observational cohort study was conducted to evaluate the efficacy and safety of osimertinib in patients with a major
mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of
mutation.
A total of 51 patients were included in this study. An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (
=0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. The median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (
=0.045). Median OS in the exon 19 deletion and L858R point mutation groups was significantly different at 19.8 months and 12.9 months, respectively (
=0.0015). Multivariate analysis identified the exon 19 deletion as a favorable independent predictor of PFS and OS.
Investigators should consider the proportions of sensitive
mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib.
Amrubicin (AMR) is an anticancer drug for patients with relapsed small-cell lung cancer (SCLC). However, the efficacy of AMR in elderly patients with relapsed SCLC after chemotherapy by carboplatin ...plus etoposide (CE) has not been sufficiently evaluated.
The medical records of patients with relapsed SCLC who received AMR as second-line chemotherapy were retrospectively reviewed, and their treatment outcomes were evaluated.
Forty-one patients with a median age of 76 years were analyzed. The overall response rate was 26.8%. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 8.1 months, respectively. While the median PFS of 4.7 and 2.8 months in the sensitive relapse and the refractory relapse group differed significantly (
=0.043), respectively, the median OS of 10.7 and 6.8 months in the respective relapse groups did not indicate a statistically significant difference (
=0.24). The median PFS in a group with a modified Glasgow prognostic score (mGPS) of 0 and a group with a mGPS 1 or 2 were 4.5 and 1.6 months (
=0.052), respectively, and the median OS in the respective mGPS groups were 10.7 and 4.4 months (
=0.034). Multivariate analysis identified good performance status, limited disease, and mGPS 0 as favorable independent predictors of PFS and OS of AMR monotherapy. Grade 3 or higher neutropenia was observed in 23 patients (56%), and febrile neutropenia was observed in nine patients (22%). Non-hematological toxic effects were relatively mild, and pneumonitis and treatment-related deaths were not observed.
AMR is an effective and feasible regimen for elderly patients with relapsed SCLC after CE therapy.
Background
Carboplatin plus etoposide (CE) is a standard treatment for elderly patients with extensive‐disease small cell lung cancer (ED‐SCLC). However, amrubicin monotherapy (AMR) may be a feasible ...alternative. We compared the efficacies and safety profiles of CE and AMR for ED‐SCLC in elderly patients and chemotherapy‐naive patients with poor performance status (PS).
Methods
The records of SCLC patients who received CE or AMR as first‐line chemotherapy were retrospectively reviewed and their treatment outcomes evaluated.
Results
Eighty‐four patients (median age 72 years; 42 each received CR and AMR) were analyzed; 34 patients had a PS score of 2. There were no significant differences in patient characteristics between the treatment groups. The median progression‐free survival rates of patients in the CE and AMR groups were 5.8 and 4.8 months, respectively (P = 0.04); overall survival was 14.0 and 8.5 months, respectively (P = 0.089). Twenty‐three CE group patients received AMR as second‐line chemotherapy; their median overall survival from first‐line chemotherapy was 18.5 months. Grade 3 or higher neutropenia occurred more frequently in patients treated with AMR (64% vs. 40%; P = 0.02), as did febrile neutropenia (14% vs. 7%).
Conclusions
CE remains a suitable first‐line treatment for ED‐SCLC in elderly patients or those with poor PS in comparison with AMR.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
【Background】 Few studies have assessed donor-specific antibodies (DSA) and anti-human leucocyte antigen (HLA) antibodies associated with the transplantation (Tx) of organs other than kidney.【Methods】 ...A total of 31 institutions participated in the current study. Patients who satisfied the study criteria were enrolled prospectively, and rituximab was used according to each institution’s clinical protocol for desensitization before Tx when patients had preexisting DSA or anti-HLA antibodies (desensitization cohort) or to treat post-Tx antibody-mediated rejection (ABMR) (ABMR treatment cohort). The desensitization cohort comprised four liver transplants, four kidney-pancreas transplants, and one heart transplant, and the ABMR treatment cohort contained two liver transplants, two heart transplants, and one lung transplant. In the desensitization cohort, organs ultimately were not allocated for the patient awaiting a heart transplant and one patient awaiting a kidney-pancreas transplant.【Results】 In the desensitization cohort, DSA or anti-HLA antibodies decreased in the four liver Tx patients and three of the kidney-pancreas Tx patients. Although T-cell mediated rejection occurred in two patients, they did not develop ABMR. One pancreatic graft was lost due to post-transplantation thrombosis; all other grafts and all patients survived. In the ABMR treatment cohort, DSA decreased after ABMR treatment in one heart Tx patient and two liver Tx patients. Acute ABMR was eliminated completely only in the patient who developed the complication early after liver Tx.【Conclusion】 Rituximab was well-tolerated, both during desensitization and as part of ABMR treatment for Tx of organs other than kidney.
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