scholarly journals KRAS mutations (KRAS-mut) and antiPD1/PDL1 therapy in a cohort of non-small cell lung cancer (NSCLC) patients (p): Experience from a single institution

2017 ◽  
Vol 28 ◽  
pp. v417 ◽  
Author(s):  
C. Erasun Lecuona ◽  
M.T. Moran Bueno ◽  
L. Vila ◽  
I. Teruel ◽  
L. Angelats ◽  
...  
Author(s):  
Stefania Nobili ◽  
Daniele Lavacchi ◽  
Gabriele Perrone ◽  
Giulio Vicini ◽  
Renato Tassi ◽  
...  

The use of vinorelbine as a single agent or in combination regimens in non-small cell lung cancer (NSCLC) is associated with satisfactory clinical activity. However, the role of vinorelbine-based chemotherapy in chemonaive locally advanced unresectable or metastatic NSCLC patients, according to real-world treatment patterns, has still not been widely explored. Eighty-one patients treated at a single institution were retrospectively analyzed. Thirty-seven received standard first-line single-agent vinorelbine, and 44 received vinorelbine plus platinum drugs, based on physician’s choice; 61.7% were older than 70 years, and 60.5% were affected by ≥2 comorbidities. Sixty-three patients were evaluable for objective response: 22% achieved partial response and 41% stable disease. Median progression-free survival (PFS) was 5.4 months. A benefit in PFS was observed in patients treated with combinations vs. single-agent vinorelbine (6.7 vs. 3.5 months, p = 0.043). Median overall survival (OS) was 10.4 months without a statistically significant difference between treatments (12.4 vs. 7.5 months). In 55 stage IV patients, OS was positively correlated with combination regimens, M1a stage, or ≤2 metastatic lesions. Grade 3‐4 toxicity occurred in 33% of patients, and dose reduction in 11%. A statistically significant higher incidence of toxicity was observed in patients receiving combinations, in women, in patients younger than 75 years, or patients with metastases. In this real-word analysis, we confirmed the efficacy and tolerability of vinorelbine as a single agent or combined with platinums in patients usually underrepresented in controlled clinical trials. Single-agent vinorelbine may represent a suitable option in elderly or unfit NSCLC patients and warrants investigation as a potential drug candidate for immunochemotherapy combination regimens.


2012 ◽  
Vol 18 (3 Supplement) ◽  
pp. A31-A31
Author(s):  
Wouter W. Mellema ◽  
Anne-Marie C. Dingemans ◽  
Egbert F. Smit ◽  
Jules Derks ◽  
Daniëlle A.M. Heideman ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5956
Author(s):  
Noriaki Sunaga ◽  
Yosuke Miura ◽  
Norimitsu Kasahara ◽  
Reiko Sakurai

Recent advances in molecular biology and the resultant identification of driver oncogenes have achieved major progress in precision medicine for non-small-cell lung cancer (NSCLC). v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) is the most common driver in NSCLC, and targeting KRAS is considerably important. The recent discovery of covalent KRAS G12C inhibitors offers hope for improving the prognosis of NSCLC patients, but the development of combination therapies corresponding to tumor characteristics is still required given the vast heterogeneity of KRAS-mutated NSCLC. In this review, we summarize the current understanding of KRAS mutations regarding the involvement of malignant transformation and describe the preclinical and clinical evidence for targeting KRAS-mutated NSCLC. We also discuss the mechanisms of resistance to KRAS G12C inhibitors and possible combination treatment strategies to overcome this drug resistance.


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