Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Systemic Immune Inflammation Index as a Key Marker of Survival and Immune-related Adverse Events in Immune Checkpoint Inhibitor Therapy.

OBJECTIVE: To evaluate the prognostic significance of the new index designed by formulating neutrophil, lymphocyte, and platelet counts in patients with metastatic disease receiving immune checkpoint inhibitors (ICI) and its effect on the immune-related adverse events (irAEs). STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, University of Manisa Celal Bayar, University of Aydin Adnan Menderes, and University of Ege, and Izmir Kent Hospital, Turkey, from January 2016 to April 2020. METHODOLOGY: Patients with metastatic disease receiving ICI sufficient follow-up data were included. Patients, who had received treatment for a minimum of 3 months, were evaluated for the response. Systemic immune-inflammation index (SII) was calculated as neutrophil (/L) × (lymphocyte (/L) / platelet (/L). The cut-off value was determined by examining the area under the receiver operating characteristic (ROC) curve for the SII value. The endpoints of this study included overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 168, patients who received ICI in the metastatic stage, were evaluated. The OS of the patients with low SII scores was 110.8 months (95% CI, 88.2-133.5), while patients with high SII scores were 36.0 months (95% CI, 28.4-43.6) and reached statistical significance (p <0.001). The results of univariate (HR=3.376, 95% CI, 1.986-5.739, p<0.001 and multivariate (HR=2.792, 95% CI, 1.495-5.215, p=0.011) analyses were statistically significant as well. CONCLUSION: The SII score in patients with metastatic disease receiving ICI was closely related to the prognosis. Patients with a high SII score are associated with a worse prognosis, these patients develop fewer irAEs. KEY WORDS: Systemic immune inflammation index, Overall survival, Progression-free survival, Immune checkpoint inhibitor, Pembrolizumab, Nivolumab.

HALP Score as a New Prognostic Index in Metastatic Renal Cell Cancer.

OBJECTIVE: To evaluate prognostic significance of the new index, designed by formulating hemoglobin, albumin, lymphocyte, and platelet (HALP) counts in patients with metastatic renal cell carcinoma (RCC). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Celal Bayar University, Manisa, Turkey and Adnan Menderes University, Aydin, Turkey, from January 2014 to April 2020. METHODOLOGY: Patients with metastatic RCC and sufficient follow-up data were included in the study as a retrospective cohort. HALP score was calculated as hemoglobin (g/L) × albumin (g/L) levels × lymphocyte count (/L)/platelet count (/L). The cut-off value was determined by examining the area under the ROC curve for the HALP value. The endpoints of this study included overall survival (OS) and progression-free survival (PFS). RESULTS: The mean overall survival (OS) of the patients with low HALP score was 17.7 months (95% CI, 2.21 - 33.18), while the OS of the patients with high HALP score was 89.7 months (95% CI, 55.62 - 123.77) and reached statistical significance (p=0.001). The results of univariate (p = 0.009) and multivariate (p=0.012) analyses were statistically significant as well. CONCLUSION: The HALP score in metastatic RCC patients was closely related to the prognosis. Worse OS was found in patients with a low HALP score. Key Words: HALP score, Overall survival, Progression-free survival, Renal cell carcinoma.

Could the Inflammatory Prognostic Index Predict the Efficacy of Regorafenib in Patients with Metastatic Colorectal Cancer?

PURPOSE: To investigate the clinical importance of the inflammatory prognostic index (IPI) in patients with metastatic colorectal cancer treated with regorafenib. METHODS: A retrospective analysis of 65 metastatic CRC patients treated with regorafenib between 2015 and 2020 was performed. The association between NLR, PNLR, IPI, and overall survival (OS) and progression-free survival (PFS) was evaluated. RESULTS: According to the cut-off points, patients were divided into two groups. The patients in the high IPI group showed poorer OS compared to patients in the low IPI groups. The PFS was better in patients with low neutrophil-lymphocyte ratio (NLR) and platelet-neutrophil to lymphocyte ratio (PNLR), and the OS was better in patients with low IPI. CONCLUSION: Among the immune inflammation scores analyzed in mCRC patients receiving regorafenib, NLR and PNLR were the best predictor of recurrence, whereas IPI was the best predictor of long-term survival. After being confirmed by better designed controlled trials, IPI can be used to identify the group of patients who will benefit more from regorafenib treatment.