Results from the phase 3 FRESCO-2 trial demonstrated a doubling of progression-free survival (PFS) and almost doubling of overall survival (OS) with VEGF-1, -2, and -3 inhibitor fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (mCRC).
The multi-TKI inhibitor regorafenib is standard-of-care in patients with (heavily) pre-treated, refractory mCRC . The original phase 3 FRESCO trial (NCT02314819) showed efficacy and safety of the VEGF-1, -2, and -3 inhibitor fruquintinib in Chinese patients with mCRC in the third (or later) line setting . However, standard-of-care for mCRC in China differed from global patterns when the original FRESCO trial was conducted (e.g. only 30% of participants had prior VEGF inhibition). To evaluate the efficacy and safety of fruquintinib in a globally more representative population, FRESCO-2 (NCT04322539) was conducted in the USA, Europe, Japan, and Australia. Prof. Nageshwara Arvind Dasari (MD Anderson Cancer Centre, TX, USA) presented the first results .
FRESCO-2 enrolled 691 patients with mCRC who had prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF therapy and –if RAS wildtype– anti-EGFR therapy. All participants had progressed in disease stage or were intolerant to TAS-102 and regorafenib, and had prior treatment with immune checkpoint inhibition or BRAF inhibition if indicated. 72% of participants had 3 or more prior treatment lines for metastatic disease. Participants were 2:1 randomised to fruquintinib (5 mg once daily, 3 weeks on, 1 week off) or placebo until progression or unacceptable toxicity. All participants received the best supportive care. The primary endpoint was OS and the key secondary endpoint was PFS.
Fruquintinib significantly improved median OS compared with placebo (7.4 vs 4.8 months; HR 0.662; P<0.001). Fruquintinib favoured OS in all pre-specified subgroups. Of note, subsequent anti-cancer medication was balanced between the arms (29.4% in the fruquintinib arm and 34.3% in the placebo arm). PFS doubled in the fruquintinib arm (3.7 vs 1.8 months; HR 0.321; P<0.001). The objective response rate was 1.5% for participants receiving fruquintinib versus 0% for placebo, whereas the disease control rate was 55.5% versus 16.1%. Grade ≥3 treatment-related adverse events (mainly hypertension and asthenia) were observed in 36% of participants in the fruquintinib arm versus 11.3% of participants in the placebo arm.
“The FRESCO-2 trial met its primary endpoint and the results are consistent with those of the FRESCO trial, supporting fruquintinib as a new, global treatment option for patients with refractory mCRC,” concluded Prof. Dasari.
- Van Cutsem E, et al. Ann Oncol. 2014; 25:(Suppl 3):iii1–iii9.
- Li J, et al. JAMA 2018; 319(24):2486–2496.
- Dasari NA, et al. FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Abstract LBA25, ESMO Congress 2022, 09–13 September, Paris, France.
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Table of Contents: ESMO 2022
Letter from the Editor
High pathological responses to neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer
Fruquintinib: a potential new treatment for patients with refractory mCRC
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
Upper Gastrointestinal Cancer
Deep learning models predict the risk of relapse and the mutational profile in GIST
Addition of pembrolizumab to lenvatinib does not improve OS in advanced HCC
New, highly selective inhibitor of FGFR2 driver alterations and resistance mutations
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel
Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer
OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant
OS benefit of sacituzumab govitecan in pre-treated HR-positive/HER2-negative metastatic breast cancer
A pathway from air pollution to lung cancer in non-smokers identified
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib
High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy
Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab
Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas
Survival-benefit of neoadjuvant T-VEC maintained over 5 years of follow-up
Baseline ctDNA predicts survival in resected stage III–IV melanoma
Genitourinary Cancer – Prostate Cancer
Overall survival benefit of abiraterone in mHSPC is maintained for 7 years
Limited benefit of adding long-term ADT to post-operative radiotherapy in prostate cancer
Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer
Genitourinary Cancer – Non-Prostate Cancer
Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy
Triple therapy improves progression-free survival in patients with advanced RCC versus dual therapy
Adjuvant atezolizumab does not improve outcomes for patients with RCC and increased risk of recurrence
OS benefit for advanced ovarian cancer patients treated with maintenance olaparib
Maintenance tegafur-uracil does not improve survival in locally advanced cervical cancer
Head and Neck Cancer
Adding first-line pembrolizumab to CRT in locally advanced HNSCC does not significantly prolong survival or event-free survival
5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC
Epstein Barr virus-specific autologous cytotoxic T lymphocytes do not improve survival in nasopharyngeal carcinoma