Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

Kato, Takeshi; Kagawa, Yutaka; Kuboki, Yasutoshi; Gamoh, Makio; Yasui, Hirofumi; Satake, Hironaga; Oki, Eiji; Tanioka, Hiroaki; Kotaka, Masahito; Makiyama, Akitaka; Denda, Tadamichi; Goto, Masahiro; Yoshino, Takayuki; Yamazaki, Kentaro; Soeda, Junpei; Shibuya, Kazunori; Iwata, Masaru; Oba, Koji; Yamaguchi, Kensei

doi:10.1007/s10147-021-01902-2

Cited by 2 publications

(2 citation statements)

References 31 publications

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“…The higher efficacy in patients with RAS wild-type and left-sided tumors also yields the question of whether bevacizumab or an anti-EGFR drug is the best combination option in these subjects. Trifluridine-tipiracil was combined with the anti-EGFR drug panitumumab in patients with wild-type RAS mCRC who were refractory/intolerant to standard therapies other than anti-EGFR therapy, yielding a median PFS and OS of 5.8 months and 14.1 months, respectively [ 23 ]. We will hopefully be able to provide a better answer to this question based on upcoming results from the phase II FIRE-8 trial [ 24 ], which aims to compare bevacizumab and panitumumab as a combination partner for trifluridine-tipiracil as first-line treatment in patients with RAS wild-type tumors, and from the phase II VELO trial [ 25 ], which is investigating a combination of trifluridine-tipiracil and panitumumab versus trifluridine-tipiracil alone as third-line therapy in patients with RAS wild-type tumors who experienced clinical response to EGFR targeting earlier lines of treatment.…”

Section: Discussionmentioning

confidence: 99%

Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer

et al. 2022

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Background The combination of trifluridine-tipiracil and bevacizumab was compared with trifluridine-tipiracil monotherapy in a randomized, open-label, phase II trial, resulting in a statistically significant and clinically relevant improvement in progression-free survival (PFS), with tolerable toxicity in patients with refractory metastatic colorectal cancer (mCRC); however, evidence supporting the role of this combination in a real-world setting is limited. Objective The aim of our work was to provide further evidence on the activity and safety of this combination in a real-world series of Western mCRC patients refractory or intolerant to previous therapies. Patient and Methods We conducted a retrospective, observational study of patients with mCRC refractory or intolerant to standard therapies. Patients were treated with trifluridine-tipiracil and bevacizumab. Previous therapy with fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab, aflibercept, regorafenib, and cetuximab or panitumumab (only RAS wild-type) was allowed, as was previous participation in clinical trials. Clinicopathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS), PFS, and safety data were retrospectively collected and analyzed. Results We recorded 31 patients treated between 1 December 2017 and 30 June 2022. Median age was 69 years (range 38–82 years), 39% were male, 100% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–1, tumor location was left-sided in 77% of cases, 54% had synchronous presentation, 35% were RAS mutant, 3% were BRAF mutant, and 71% underwent primary tumor resection; 64% of patients had liver metastases, 55% had lung metastases, and 23% had peritoneal carcinomatosis. The median number of previous treatment lines was 2 (range 0–5), and 84% of patients received at least one previous anti-angiogenic agent. The ORR and DCR were 3% and 71%, respectively. With a median follow-up of 8 months (range 2–39), median PFS was 6 months (95% confidence interval [CI] 3.1–8.9 months) and median OS was 14 months (95% CI 10.1–17.8 months). Adverse events of any grade were reported in 58% of patients. The most common grade 3–4 toxicities were neutropenia (19%) and anemia (6%); 35% of patients required either dose delays or dose reductions due to toxicity. Granulocyte colony-stimulating factor (G-CSF) prophylaxis was administered either on first or subsequent cycles of treatment in 35% of patients. No treatment-related deaths occurred. Sixty percent of the patients who discontinued treatment eventually received one or more lines of subsequent therapy. Conclusions Our series provides further evidence on the activity and safety of the combination of trifluridine-tipiracil and bevacizumab in a real-world series of Western refractory mCRC patients.

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Section: Discussionmentioning

confidence: 99%

Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer

et al. 2022

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“…In that study, for patients with mCRC, TAS-102 plus bevacizumab as a third-line treatment achieved a median PFS of 4.5 months (95% CI, 1.8-7.1) and median OS of 9.2 months (95% CI, 5.5-12.8) ( 15 ). In addition, in the APOLLON study, the median PFS and OS of patients with wild-type RAS mCRC treated with TAS plus panitumumab were 5.8 months (95% CI, 4.5-6.5) and 14.1 months (95% CI, 12.2-19.3), respectively ( 16 ). The results of these studies are encouraging, and thus, clinicians should further explore TAS-102 combination therapy for mCRC to extend time benefits for patients.…”

Section: Discussionmentioning

confidence: 99%

Anlotinib combined with TAS-102 as the third-line treatment for a patient with metastatic colon cancer: A case report

Zhang

Fan

et al. 2022

Front. Oncol.

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Chemotherapy combined with targeted therapy is a first-line and second-line treatment for metastatic colorectal cancer(mCRC), which has brought survival benefits to mCRC patients, however, disease progression is inevitable. More than 60% of patients still needed third-line treatment after the progress of second-line treatment. After the failure of second-line chemotherapy, treatment compliance and the physical tolerance of patients both decrease. Therefore, choosing an appropriate third-line treatment regimen is key to prolonging survival and improving quality of life. As a novel cytotoxic antitumor drug, trifluridine/tipiracil (TAS-102) is composed of trifluridine (FTD) and tipiracil hydrochloride (TPI). FTD can directly bind to the DNA of cancer cells to cause DNA dysfunction, thereby exerting antitumor effects. TPI can inhibit the degradation of FTD, thereby increasing its cytotoxicity. The few side effects of TAS-102 has become an important reason why clinicians present it as a treatment option to the patient for consideration, clinical trial data for progression free survival are lacking. The exploration of third-line treatment regimens with drug combinations has attracted much attention. This article reports a case of metastatic colon cancer (RAS/BRAF wild type, pMMR/Non-MSI-H), after failure of first-line and second-line therapies, the patient was eventually treated with anlotinib combined with TAS-102 as the third-line treatment. The treatment has shown good efficacy, with a long PFS benefit for more than 20 months and mild adverse reactions. This case reports demonstrates that anlotinib combined with TAS-102 is a promising third-line treatment regimen for refractory mCRC, and provides proof-of-concept for the clinical exploration of optimal third-line combination treatment regimens.

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Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

Cited by 2 publications

References 31 publications

Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer

Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer

Anlotinib combined with TAS-102 as the third-line treatment for a patient with metastatic colon cancer: A case report

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