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Background and Aims: In patients with Rat sarcoma proto-oncogene (RAS) wild-type metastatic colorectal cancer (mCRC), anti-epidermal growth factor receptor (EGFR) antibodies have been established in first- and further therapy lines. Due to limited treatment options upon disease progression, anti-EGFR re-exposure is increasingly employed in real-world oncology. The aim of this study was to assess clinical implementation and utility of anti-EGFR retreatment strategies in real-world mCRC patients. Methods: In this monocentric retrospective study, we included 524 patients with CRC and identified patients who received an anti-EGFR-based treatment as well as anti-EGFR rechallenge (progression on first-line anti-EGFR therapy) or reintroduction (discontinuation due to intolerance/toxicity/other). Results: In total, 143 patients received an anti-EGFR-based first- or second-line treatment, showing a similar overall survival (OS) compared to the non-anti-EGFR treatment group (38.3 vs. 39.6 months, p = 0.88). Thirty-three patients met the inclusion criteria for anti-EGFR re-exposure and were either assigned to rechallenge (n = 21) or reintroduction (n = 12) subgroups. The median FU after re-exposure was 45.8 months. Cetuximab and Panitumumab were used in 21 and 12 patients, respectively, and the main chemotherapy at re-exposure was FOLFIRI in 39.4%. Anti-EGFR re-exposure was associated with a distinct trend towards a better outcome (median OS 56.0 vs. 35.4 months, p = 0.06). In a subgroup comparison, reintroduction was associated with a higher OS and PFS in trend compared to the rechallenge (mOS 66 vs. 52.4, n.s., mPFS 7.33 vs. 3.68 months, n.s.). Conclusions: This retrospective study provides real-world evidence underscoring that anti-EGFR re-exposure strategies might benefit patients independently of the reason for prior discontinuation.
Introduction: Scarce data exist for therapy regimens other than somatostatin analogues (SSA) and peptide receptor radiotherapy (PRRT) for siNET. We analyzed real world data for differences in survival according to therapy. Patients and methods: Analysis of 145 patients, diagnosed between 1993 and 2018 at a single institution, divided in treatment groups. Group (gr.) 0: no treatment (n = 10), gr 1: TACE and/or PRRT (n = 26), gr. 2: SSA (n = 32), gr. 3: SSA/PRRT (n = 8), gr. 4: chemotherapy (n = 8), gr. 5: not metastasized (at diagnosis), surgery only (n = 53), gr. 6 = metastasized (at diagnosis), surgery only (n = 10). Results: 45.5% female, median age 60 years (range, 27–84). A total of 125/145 patients with a resection of the primary tumor. For all patients, 1-year OS (%) was 93.8 (95%-CI: 90–98), 3-year OS = 84.3 (CI: 78–90) and 5-year OS = 77.5 (CI: 70–85). For analysis of survival according to therapy, only stage IV patients (baseline) that received treatment were included. Compared with reference gr. 2 (SSA only), HR for OS was 1.49 (p = 0.47) for gr. 1, 0.72 (p = 0.69) for gr. 3, 2.34 (p = 0.19) for gr. 4. The 5 y OS rate of patients whose primary tumor was resected (n = 125) was 73.1%, and without PTR was 33.3% (HR: 4.31; p = 0.003). Individual patients are represented in swimmer plots. Conclusions: For stage IV patients in this analysis (limited by low patient numbers in co. 3/4), multimodal treatment did not significantly improve survival over SSA treatment alone. A resection of primary tumor significantly improves survival.
Background and Aims. Systemic treatment with sorafenib has been the standard of care (SOC) in patients with advanced Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) for more than a decade. TACE has been reported to allow better local tumor control in selected patients with BCLC stage C HCC. Methods. A retrospective analysis of patients with BCLC stage C HCC that were treated with sorafenib and TACE was conducted; they were compared to BCLC stage C patients treated either with TACE or sorafenib in the same period of time outside a clinical trial. Results. A total of 201 patients with BCLC stage C were identified, who were treated with either sorafenib and TACE (group A; n = 54), sorafenib (group B; n = 82) or TACE (group C; n = 65). No significant difference in baseline characteristics was observed. Time to progression was 7.0 months (95% CI: 4.3–9.7), 4.1 months (95% CI: 3.6–4.7) and 5.0 months (95% CI: 2.9–7.1) in groups A, B and C, respectively, and overall survival was 16.5 months (95% CI: 15.0–18.1), 8.4 months (95% CI: 6.0–10.8) and 10.5 months (95% CI: 7.5–13.6), respectively (group A vs. group B: p < 0.001; group A vs. group C: p = 0.0023). Adverse events of grade 3/4 occurred in 34% of patients in group A. Conclusions. Although sorafenib is a SOC in patients with BCLC stage C HCC, TACE is frequently used as an additional locoregional treatment in selected patients. This combined approach resulted in a significant overall survival benefit in selected patients, although randomized trials have not yet proven this benefit.
Background: Patients with colorectal carcinoma and high-grade microsatellite instability (MSI-H) or deficiency in mismatch repair (dMMR) exceptionally respond to immune checkpoint inhibitors (ICIs). ICIs are more active in treatment-naïve patients than in patients with refractory MSI-H/dMMR metastatic colorectal cancer and even more active in patients with locally advanced tumors. Material and Methods: A 33-year-old male patient with Lynch syndrome was diagnosed with a locally advanced rectal cancer and refused standard neoadjuvant chemoradiation because of the potential harm of sexual dysfunction. MMR and microsatellite instability status were analyzed by immunohistochemistry and fragment length polymerase chain reaction followed by capillary electrophoresis. Results: After MSI-H/dMMR was confirmed, the patient was treated with ICIs (1 mg/kg ipilimumab at day 1 and 3 mg/kg nivolumab at day 1 and 15). A complete clinical response was documented at day 21 after start of treatment. The patient underwent a total mesorectal excision at day 30. In the extirpated tissue, a complete pathological response was confirmed. Conclusion: In MSI-H/dMMR locally advanced rectal cancer short-course ICI treatment is highly effective and may be discussed in patients with dMMR locally advanced rectal cancer.
Background: Patients with colorectal carcinoma and high-grade microsatellite instability (MSI-H) or deficiency in mismatch repair (dMMR) exceptionally respond to immune checkpoint inhibitors (ICIs). ICIs are more active in treatment-naïve patients than in patients with refractory MSI-H/dMMR metastatic colorectal cancer and even more active in patients with locally advanced tumors. Material and Methods: A 33-year-old male patient with Lynch syndrome was diagnosed with a locally advanced rectal cancer and refused standard neoadjuvant chemoradiation because of the potential harm of sexual dysfunction. MMR and microsatellite instability status were analyzed by immunohistochemistry and fragment length polymerase chain reaction followed by capillary electrophoresis. Results: After MSI-H/dMMR was confirmed, the patient was treated with ICIs (1 mg/kg ipilimumab at day 1 and 3 mg/kg nivolumab at day 1 and 15). A complete clinical response was documented at day 21 after start of treatment. The patient underwent a total mesorectal excision at day 30. In the extirpated tissue, a complete pathological response was confirmed. Conclusion: In MSI-H/dMMR locally advanced rectal cancer short-course ICI treatment is highly effective and may be discussed in patients with dMMR locally advanced rectal cancer.