Sotorasib in KRAS G12C-mutated non-small cell lung cancer: A multicenter real-world experience from the compassionate use program in Germany.

BACKGROUND: Sotorasib is a first-in-class KRAS p.G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) in 2018. First response rates were promising in the CodeBreaK trials. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients underrepresented in clinical trials. METHODS: Patients with KRAS p.G12C-mutated advanced or metastatic NSCLC received sotorasib within the German multicenter sotorasib compassionate use program between 2020 to 2022. Data on efficacy, tolerability, and survival were analyzed in the full cohort and in subgroups of special interest such as co-occurring mutations and across PD-L1 expression levels. RESULTS: We analyzed 163 patients who received sotorasib after a median of two treatment lines (range, 0 to 7). Every fourth patient had a poor performance status and 38% had brain metastases (BM). The objective response rate was 38.7%. The median overall survival was 9.8 months (95% CI, 6.5 to not reached). Median real-world (rw) progression-free survival was 4.8 months (9% CI, 3.9 to 5.9). Dose reductions and permanent discontinuation were necessary in 35 (21.5%) and 7 (4.3%) patients, respectively. Efficacy seems to be influenced by PD-L1 expression and a co-occurring KEAP1 mutation. KEAP1 was associated with an inferior survival. Other factors such as BM, STK11, and TP53 mutations had no impact on response and survival. CONCLUSION: First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit.

[Chylous ascites in NSCLC: It is not always malignant]. / Chylöser Aszites bei NSCLC: Nicht alles ist maligne, was maligne aussieht.

The etiology of chylous ascites is multifactorial. Malignant diseases, cirrhosis, trauma, lymphomatic abnormalities and mycobacteriosis are the most common causes. In NSCLC, chylous ascites is observed with peritoneal metastasis or abdominal lymph node metastases.RET alterations occur in 1-2% of NSCLC patients and since recently they can be treated in a targeted fashion.Our case report shows that new targeted therapies revolutionize prognosis, but confront us with the challenge of new and partly unknown side effects.

Effect of antimicrobial therapy on progression-free survival of immunotherapy and chemo-/immunotherapy in patients with non-small cell lung cancer.

BACKGROUND: The choice between immunotherapy with a checkpoint inhibitor (CPI) and chemo-/immunotherapy (CIT) in patients with NSCLC stage IV is often discussed. There are some data that the effect of CPI therapy is impaired by antimicrobial therapy (AMT). Little is known about the influence of AMT on CIT. PATIENTS AND METHODS: We retrospectively analysed 114 patients (age 68 ± 8.5 years) with NSCLC stage IV. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab, cemiplimab) or CIT (Carboplatin/Pemetrexed/Pembrolizumab, Carboplatin/Paclitaxel/Pembrolizumab). We registered patients' characteristics including presence and timing of AMT. Group 1 consisted of 42 patients with AMT in the month before CPI or CIT, group 2 were 49 patients with AMT during CPI or CIT, and group 3 were 64 patients without AMT and CPI or CIT. RESULTS: Group 1-3 showed comparable patients characteristics. Using cox-regression analysis, we found that AMT in the month before CPI resulted in a decreased progression-free survival (PFS) compared to patients with CPI and no AMT (14 ± 1.02 vs. 4 ± 1.02 months, p = 0.002, 95% CI 1.88-9). In patients, who were treated with CIT, there was no difference in PFS in those with or without AMT in the month before therapy (10 ± 2.5 vs. 6 ± 1.2 months, p = 0.7). Interestingly, AMT during CIT or CPI therapy showed no effect on PFS. CONCLUSIONS: In a real-life setting, we found that AMT reduces PFS when given in the month before CIT therapy. AMT before or during CIT does not seem to influence PFS. As a consequence, AMT before start of therapy might be a factor that could lead to a preference of CIT instead of CPI in NSCLC stage IV patients.

[Viral meningitis: a rare cause of hyperventilation]. / Virale Meningoenzephalitis: eine seltene Ursache der Hyperventilation.

The etiology of hyperventilation is multifactorial. When excluding somatic causes, neurogenic hyperventilation must always be considered. Since hyperventilation itself causes neuromuscular symptoms such as paresthesia, vertigo, cephalgia, and nausea, the differential diagnosis of viral meningitis in the presence of hyperventilation is not always obvious and can easily be overlooked. Our case report shows that somatogenic causes of hyperventilation should be carefully excluded.

Effect of antimicrobial therapy on progression-free survival of patients with non-small cell lung cancer receiving checkpoint inhibitor- and chemotherapy.

BACKGROUND: Checkpoint inhibitor therapy (CPI) has significantly changed therapy in non-small cell lung cancer (NSCLC) in recent years. There are some data that the effect of CPI therapy is influenced by the microbiome. Little is known about the influence and timing of antimicrobial therapy (AMT) on the microbiome-mediated effect on CPI therapy. PATIENTS AND METHODS: We retrospectively analysed 70 patients (age 68 ± 9.2 years) with NSCLC stage IV. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab) or chemotherapy (platin doublet or docetaxel/nintedanib or pemetrexed). We registered patient's characteristics including presence and timing of AMT. Group 1 consisted of 27 patients with AMT in the month before CPI- or chemotherapy, group 2 was 30 patients with AMT during CPI- or chemotherapy, and group 3 was 43 patients without AMT. RESULTS: Groups 1-3 showed comparable patient characteristics. Using cox-regression analysis, we found that AMT in the month before CPI resulted in a decreased progression-free survival (PFS) compared to patients with CPI and no AMT (14 ± 1.56 vs. 5 ± 0.99, p = 0.005, 95% CI: 0.13-0.67). In patients, who were treated with chemotherapy alone, there was no difference in PFS in those with or without AMT in the month before therapy (5 ± 0.99 vs. 6 ± 0.81 months, p = 0.3). Interestingly, AMT during chemotherapy or CPI therapy showed no effect on PFS. CONCLUSIONS: In a real-life setting, we found that AMT reduces PFS when given in the month before CPI therapy. AMT before chemotherapy and during CPI and chemotherapy seems not to influence PFS. The best PFS was seen in patients without AMT before CPI therapy. This implies the need for an even more restrictive use of AMT in the context of patients with NSCLC stage IV disease.

Carbondioxide-Aided Angiography Decreases Contrast Volume and Preserves Kidney Function in Peripheral Vascular Interventions.

Chronic kidney disease is a common comorbidity in patients with peripheral artery disease. We investigated the safety and efficacy of carbon dioxide (CO2) as supplemental contrast agent to decrease contrast volume during fluoroscopy-guided peripheral vascular procedures in routine angiological practice. We analyzed 191 consecutive interventions of the lower extremity in claudicants and critical limb ischemia (CLI) that were performed with iodinated contrast media (ICM) alone (n = 154) or with the aided or exclusive use of CO2 (n = 37). The technical success rate, total irradiation, and intervention time were not significantly different between ICM and CO2 No severe procedure-related complications occurred. The contrast volume was lower in CO2 than in ICM. Although kidney function, creatinine, and estimated glomerular filtration rate was lower in CO2 at baseline, the incidence of contrast-induced nephropathy was lower in CO2 compared to ICM. These data support CO2 as an alternative supplemental contrast agent that can be applied safely and efficiently to lower contrast volume during peripheral vascular interventions preventing kidney dysfunction even in patients with disease of the popliteal artery and below the knee and CLI.