Background
The standard treatment for patients with unresectable locally advanced (LA) non‐small cell lung cancer (NSCLC) is chemoradiotherapy (CRT). Consolidation therapy with durvalumab after CRT ...demonstrated survival benefits and was approved in Japan in July 2018. The use of immune checkpoint inhibitors (ICIs) is entering routine oncological practice, and here we investigate the feasibility of concurrent CRT for LA‐NSCLC patients based on the PACIFIC criteria.
Methods
We performed a retrospective study to evaluate the feasibility and efficacy of concurrent CRT prior to the approval of durvalumab. We assessed consecutive patients with LA‐NSCLC treated with CRT between January 2012 and June 2018.
Results
We analyzed a total of 108 consecutive patients who received radical thoracic radiotherapy and concurrent platinum‐based chemotherapy. Of those patients, 105 (97%) completed the planned radiotherapy. Radiation pneumonitis was observed in 93 patients (85%), with a median of 130 days (range: 41–317 days) from the initiation of radiation to the onset of the complication. Among the patients, 74 (69%) were considered eligible for consolidation therapy with durvalumab. The overall response rate was 64%, and the two‐year survival rate was 63%. Patients who received an ICI after relapse were associated with significantly better survival than those who did not receive an ICI (two‐year survival rate: 87% vs. 41%, respectively; P = 0.001).
Conclusions
Prior to the approval of durvalumab, the clinical application of ICIs improved the outcome of patients with relapsed NSCLC after CRT for LA‐NSCLC. The management of radiation pneumonitis remains a challenge following the approval of durvalumab.
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.
The advancement of cancer genomics has allowed for multiplex gene assays using next-generation sequencing (NGS) to be practically implemented, however, a clinical practice system remains to be ...established.
We evaluated the feasibility of clinical sequencing using NGS-based multiplex gene assays between cooperating medical institutions in patients with advanced cancers.
In this observational study, DNA and RNA samples prepared from existing tumor tissues were subjected to comprehensive genomic profiling using targeted sequencing.
From January 2017 to March 2019, 36 samples from 33 patients were assessed. Of all patients, 27 (82%) had lung cancer, with the median age of 50 years (range 38-83). Multiplex gene panel tests were successfully carried out on 35/36 (97%) samples. Potentially actionable gene alterations were identified in 10/30 (33%) samples (3 HER2, 2 KRAS, 2 ALK, 1 PIK3CA, 1 RET, and 1 CDKN2A). In the 6 samples examined for resistant mechanisms, ALK I1171N mutation and MET copy number gain were detected in 2 patients with ALK rearrangement-positive lung cancer.
Clinical sequencing using NGS-based multiplex gene assays between collaborating domestic medical institutions was feasible, with a success rate of > 97%. Overall, clinical sequencing benefits therapeutic decision-making in patients with advanced cancer.
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.
It is generally accepted for Escherichia coli that (i) the level of OmpC increases with increased osmolarity when cells are growing in neutral and alkaline media, whereas the level of OmpF decreases ...at high osmolarity, and that (ii) the two-component system composed of OmpR (regulator) and EnvZ (sensor) regulates porin expression. In this study, we found that OmpC was expressed at low osmolarity in medium of pH below 6 and that the expression was repressed when medium osmolarity was increased. In contrast, the expression of ompF at acidic pH was essentially the same as that at alkaline pH. Neither OmpC nor OmpF was detectable in an ompR mutant at both acid and alkaline pH values. However, OmpC and OmpF were well expressed at acid pH in a mutant envZ strain, and their expression was regulated by medium osmolarity. Thus, it appears that E. coli has a different mechanism for porin expression at acid pH. A mutant deficient in ompR grew slower than its parent strain in low-osmolarity medium at acid pH (below 5.5). The same growth diminution was observed when ompC and ompF were deleted, suggesting that both OmpF and OmpC are required for optimal growth under hypoosmosis at acid pH.
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