English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

KRAS  G12D-mutant/p53-deficient non-small-cell lung cancer (NSCLC) models are dependent on the NF-κB pathway that can be down-regulated by the proteasome inhibitor bortezomib. Two exceptional responders were observed on prior clinical trials of bortezomib, both of whom had  KRAS  G12D-mutant NSCLC, prompting the initiation of this single-center phase 2 trial. Patients with advanced  KRAS  G12D-mutant NSCLC were eligible. Bortezomib was administered at 1.3 mg/m 2  subcutaneously (days 1, 4, 8, 11; 21-d cycle) until progression or unacceptable toxicity. The primary objective was best objective response (RECIST v1.1). Sixteen patients with  KRAS  G12D-mutant lung adenocarcinomas were treated. Patients had a median pack year smoking history of 4 (range 0–45). A partial response (PR) was observed in one patient (−66% from baseline) and stable disease in five patients on the first stage of this study (overall response rate of 6%, 95% CI: 0.2–30.2), and further patients were not accrued. The median progression-free survival was 1 mo (95% CI: 1–6). The median overall survival was 13 mo (95% CI: 6–NA). The most common treatment-related adverse events were fatigue (38%) and diarrhea (26%).  TP53  status did not predict response on exploratory testing. Of note, the patient with a PR had a unique subtype of lung adenocarcinoma—invasive mucinous adenocarcinomas (IMA)—and had rapid clinical improvement and substantial disease regression, which was also previously observed in two other patients with advanced  KRAS  G12D-mutant lung cancer with IMAs who received bortezomib on separate clinical trials. Exceptional responses to bortezomib can be achieved in  KRAS  G12D-mutant NSCLCs.  KRAS  G12D mutation alone, however, is not a robust predictor of response. Further evaluation should only be performed after further elucidation of other factors such as co-occurring alterations and histologic subtype such as IMA that may predict sensitivity to therapy.

Exceptional responders with invasive mucinous adenocarcinomas: a phase 2 trial of bortezomib in patients with KRAS G12D-mutant lung cancers