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Povzetek: BRAF and cMET exon 14 skipping are rare mutations of NSCLC. The treatment sequence in these cases for the first and second line is not clear. An international registry was created for patients with advanced NSCLC harboring BRAF or cMET exon 14 skipping mutations, diagnosed from January 2017 to June 2022. Clinicopathological and molecular data and treatment patterns were recorded. Data on 58 patients, from eight centers across five countries, were included in the final analysis. We found that 40 patients had the cMET exon 14 skipping mutation and 18 had the BRAF V600E mutation. In total, 53 and 28 patients received first- and second-line treatments, respectively, among which 52.8% received targeted therapy (TT) in the first line and 53.5% in the second line. The overall response rate (ORR) and disease control rate (DCR) for first-line treatment with TT vs. other treatment such as immune checkpoint inhibitors ± chemotherapy (IO ± CT) were 55.6% vs. 21.7% (p = 0.0084) and 66.7% vs. 39.1% (p = 0.04), respectively. The type of treatment in first-line TT vs. other affected time to treatment discontinuation (TTD) was 11.6 m vs. 4.6 m (p= 0.006). The overall survival for the whole group was 15.4 m and was not statistically affected by the type of treatment (19.2 m vs. 13.5 m; p = 0.83).
Ključne besede: non-small-cell lung cancer, BRAF V600 mutation, cMET exon 14 skipping mutation, real-world data, targeted therapy, first-line therapy
Objavljeno v DiRROS: 25.02.2026; Ogledov: 274; Prenosov: 146
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Povzetek: Cytokine release syndrome (CRS) is a well-described immune-related adverse event following chimeric antigen receptor T-cell therapy (CAR-T) but has rarely been reported following therapy with immune checkpoint inhibitors (ICI). We present a clinical case of severe CRS after ICI therapy for advanced non-small-cell lung cancer (NSCLC). After the third cycle of ipilimumab and nivolumab the patient presented with fever, hypotension and somnolence, leading to acute respiratory failure, acute kidney and hepatic failure, capillary leak syndrome, requiring ICU (intensive care unit) care. She recovered after receiving tocilizumab and steroid therapy. Subsequently, we found 17 clinical cases of advanced NSCLC patients in peer review, experiencing CRS as an adverse event of treatment with ICI. We review those cases in detail and compare the similarities and outcomes. Conclusion: CRS is a serious, life-threatening complication that is rare after ICI therapy for solid cancers but becoming increasingly frequent since ICI therapies are broadening indications. When presented with clinical symptoms, considering CRS is crucial, as early recognition is key to timely intervention and favorable outcome for the patient.
Ključne besede: on-small-cell lung cancer, immune checkpoint inhibitors, cytokine release syndrome, immune- related adverse events, case report
Objavljeno v DiRROS: 22.08.2025; Ogledov: 597; Prenosov: 326
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Povzetek: Chemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the us-age of gemcitabine.Patients and methods. We retrospectively analysed unresectable stage III NSCLC patients who were treated with durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treat-ment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding baseline characteristic of patients.Results. Eighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during con-current treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12–99 days) from the end of the RT and were treated with the median of 10.8 (range 0.5–12 months) months. Forty-one patients (48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 24-month PFS were 71% (95% CI: 61.2–80.8%) and 45.8% (95% CI: 32.7–58.9%). With the median follow-up time of 23 months (range 2–35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% (95% CI: 79.5–93.9%) and 68.6% (95% CI: 57.2–79.9%).Conclusions. Our survival data are comparable with published research as well as with recently published real-world reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was efficient and well tolerated.
Ključne besede: non-small cell lung cancer, stage III, chemoradiotherapy, durvalumab, acute toxicity
Objavljeno v DiRROS: 23.07.2024; Ogledov: 1350; Prenosov: 402
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Ključne besede: EGFR mutations, non-small cell lung cancer, survival, metastases
Objavljeno v DiRROS: 05.07.2024; Ogledov: 1170; Prenosov: 395
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Povzetek: EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24–45). The response rate in treatment-naïve patients was 27% (95% CI, 8–58). The median progression-free and overall survival was 5 months (95% CI, 3.5–6.5) and 12 months (95% CI, 6.8–17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.
Ključne besede: medicina, non-small cell lung cancer, EGFR exon 20 inhibitors, mobocertinib, real-world data, exon 20 insertion
Objavljeno v DiRROS: 19.06.2024; Ogledov: 1290; Prenosov: 863
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