Regorafenib or rechallenge chemotherapy: which is more effective in the third-line treatment of metastatic colorectal cancer?

Köstek, Osman; Hacıoğlu, Muhammet Bekir; Sakin, Abdullah; Demir, Tarık; Sarı, Murat; Ozkul, Ozlem; Araz, Murat; Doğan, Aysun; Demircan, Nazım Can; Uzunoğlu, Sernaz; Çiçin, İrfan; Erdoğan, Bülent

doi:10.1007/s00280-018-3713-6

Cited by 17 publications

(13 citation statements)

References 19 publications

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“…Our study was the fourth retrospective study to evaluate the efficacy of chemotherapy rechallenge with either TFP/TPI or regorafenib. In a study by Kostek et al, 19 104 patients with mCRC who failed two lines of therapy were retrospectively evaluated according to the type of third-line therapy received. Patients who progressed to first-line therapy within 3 months were excluded from the study.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Chemotherapy Rechallenge Versus Regorafenib or Trifluridine/Tipiracil in Third-Line Setting of Metastatic Colorectal Cancer: A Multicenter Retrospective Comparative Study

Bazarbashi,

Alkhatib,

Aseafan

et al. 2024

JCO Glob Oncol

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PURPOSE Metastatic colorectal cancer (mCRC) is a significant global health burden. This retrospective study compared the effectiveness of trifluridine/tipiracil (FTD/TPI), regorafenib, and chemotherapy rechallenge for third-line mCRC treatment. MATERIALS AND METHODS We reviewed the medical records of 132 patients with mCRC treated with regorafenib, FTD/TPI, or a rechallenge with the initial chemotherapy regimen in a third-line setting from four different institutions. The primary end point was progression-free survival (PFS). Secondary end points were objective response rate and overall survival (OS) across the three treatment approaches. RESULTS Twenty-nine patients received chemotherapy rechallenge, and 103 received FTD/TPI or regorafenib. Patients' characteristics were comparable, except for a lower number of left-sided primaries and KRAS wild-type tumors in the FTD/TPI-regorafenib group. The median PFS for the entire group was 3.0 months, and the median OS was 13.7 months. Chemotherapy rechallenge has resulted in a median PFS of 3.1 months and a median OS of 21.2 months, compared with 2.9 months (PFS) and 12.6 months (OS) for the FTD/TPI-regorafenib group. Multivariate analyses identified male sex and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 as independent prognostic factors for better PFS, whereas chemotherapy rechallenge, localized stage at diagnosis, and an ECOG PS of 0-1 were significant prognostic factors for better OS. CONCLUSION This study suggests that chemotherapy rechallenge may provide a survival benefit in the third-line treatment of mCRC. However, patient characteristics, such as sex and ECOG PS, should also be considered in treatment decisions. Further prospective studies are required to confirm our findings.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Chemotherapy Rechallenge Versus Regorafenib or Trifluridine/Tipiracil in Third-Line Setting of Metastatic Colorectal Cancer: A Multicenter Retrospective Comparative Study

Bazarbashi,

Alkhatib,

Aseafan

et al. 2024

JCO Glob Oncol

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“…As a frequently applicated third-line option, the efficacy of chemotherapy has been discussed in previous studies. A Japanese study demonstrated that chemotherapy rechallenge was a valuable option [ 22 ]. The clinical benefit rate of oxaliplatin or irinotecan re-challenge was reported to be 75.5% in an American cohort [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study

Duan,

Zhu,

Shi

et al. 2024

BMC Cancer

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Background There are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy. Methods Using electronic medical records of patients with mCRC, a retrospective cohort study was conducted. A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting as control group were retrospectively collected. Baseline characteristics were analyzed using the χ² test or the Fisher’s exact test. ROC curve and surv_cutpoint function of ‘survminer’ package in R software were used to calculate the cut-off value. Survival curves were plotted with the Kaplan-Meier method and were compared using the log-rank test. The Cox proportional hazard regression model was used to analyze the potential risk factors. Results A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting were retrospectively collected. Chemotherapy rechallenge was recorded in 93 patients (93/143, 65.0%), and the remaining patients chose new chemotherapeutic drugs that had not been previously used, including irinotecan-based (22/50), oxaliplatin-based (9/50), raltitrexed (9/50), gemcitabine (5/50) and other agents (5/50). The ORR and DCR of third-line chemotherapy reached 8.8%, 61.3%, respectively (anti-angiogenic monotherapy group: ORR 2.6%, DCR 47.4%). The mPFS and mOS of patients receiving chemotherapy were 4.9 and 12.0 m, respectively (anti-angiogenic monotherapy group: mPFS 2.7 m, mOS 5.2 m). Subgroup analyses found that patients with RAS/RAF mutation, longer PFS (greater than 10.6 m) in front-line treatment or larger tumor burden had better prognosis with third-line chemotherapy rather than anti-angiogenic monotherapy. Conclusions Third-line chemotherapy re-use was effective in mCRC. Those with more aggressive characteristics (RAS/RAF mutant, larger tumor burden) or better efficacy of previous chemotherapy (longer PFS) were more appropriate for third-line chemotherapy, rather than anti-angiogenic monotherapy.

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“…Evaluation of the PBTs may assist phase 3 trials to investigate: long survival, sequential therapy, GFLIO in comparison to its component steps and to other regimens, safety, novel dosages, time to introduce either DM, or target drugs and the strategies incorporated in the algorithm. The latter includes re-challenge to reverse the resistance of tumors with recombined and supplementary new drugs; safety with novel, severely reduced dosages; combinations consisting of � 4 synergistic drugs compared to 1-2 drugs; and development of the regimen with additional drugs that satisfy novel laboratory criteria [10,18,[32][33][34][35][36].…”

Section: Plos Onementioning

confidence: 99%

“…The use of PBTs may increase in importance in parallel with the need to evaluate new phase 2 regimens that have produced MSTs of about 18 months for selected patients with Karnofsky scores of 100-80. These new phase 2 trials also investigate individual strategies which are integrated in GFLIO: re-challenge, ± immunotherapy, the addition of taxanes, cetuximab, or bevacizumab, gemcitabine, and irinotecan [15,16,[32][33][34][35][37][38][39].…”

Section: Plos Onementioning

confidence: 99%

Actionable tests and treatments for patients with gastrointestinal cancers and historically short median survival times

et al. 2022

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Background Patients have difficult unmet needs when standard chemotherapy produces a median survival of less than 1 year or many patients will experience severe toxicities. Blood tests can predict their survival. Methods Analyses evaluate predictive blood tests to identify patients who often survive 1 and 2 years. A four-test model includes: albumin, absolute neutrophil count, neutrophil-lymphocyte ratio, and lymphocyte-monocyte ratio. Individual tests include: alkaline phosphatase, lymphocytes, white blood count, platelet count, and hemoglobin. Eligible patients have advanced: resistant 3rd line colorectal, and both resistant and new pancreatic and intrahepatic bile duct cancers. Eligibility characteristics include: biopsy-proven, measurable metastatic disease, NCI grade 0–2 blood tests, Karnofsky Score 100–50, and any adult age. Drugs are given at 1/4–1/3 of their standard dosages biweekly: gemcitabine, irinotecan, fluorouracil, leucovorin, and day 2 oxaliplatin every 2 weeks. In case of progression, Docetaxel is added (except colon cancer), with or without Mitomycin C, and next cetuximab (except pancreatic and KRAS BRAF mutation cancers). Bevacizumab is substituted for cetuximab in case of another progression or ineligibility. Consent was written and conforms with Helsinki, IRB, and FDA criteria (FDA #119005). Results Median survival is 14.5 months. Of 205 patients, 60% survive 12, and 37% survive 24 months (95% CI ± 8%). Survival is > 24, 13, and 3.8 months for patients with 0, 1–2, and 3–4 unfavorable tests, respectively. Individual “favorable and unfavorable” tests predict long and short survival. Neither age nor prior therapy discernibly affects survival. Net rates of clinically significant toxicities are less than 5%. Conclusion Treatments reproduce predictable, greater than 12 and 24-month chances of survival for the aged and for patients with drug-resistant tumors. Evaluation of blood tests may change practice, expand eligibility, and personalize treatments. Findings support investigation of drug combinations and novel dosages to reverse resistance and improve safety.

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Regorafenib or rechallenge chemotherapy: which is more effective in the third-line treatment of metastatic colorectal cancer?

Cited by 17 publications

References 19 publications

Efficacy of Chemotherapy Rechallenge Versus Regorafenib or Trifluridine/Tipiracil in Third-Line Setting of Metastatic Colorectal Cancer: A Multicenter Retrospective Comparative Study

Efficacy of Chemotherapy Rechallenge Versus Regorafenib or Trifluridine/Tipiracil in Third-Line Setting of Metastatic Colorectal Cancer: A Multicenter Retrospective Comparative Study

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study

Actionable tests and treatments for patients with gastrointestinal cancers and historically short median survival times

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