FRESCO-2 Study Sings ESMO, Re-Composing the "Life Fur Sound" in Patients with Advanced CRC

*For medical professionals only

Professor Li Jin and Professor Chen Gong take you to preemptively interpret the wonderful content of FRESCO-2 research!

With the debut of FRESCO research at the 2017 Annual Meeting of the Chinese Society of Clinical Oncology (CSCO), fruquintinib has successfully ranked among the drug treatment of advanced colorectal cancer (CRC) in China and has become the "standard protocol"

From FRESCO to FRESCO-2 –

Fruquintinib provides a "constant" survival benefit for patients with advanced CRC

The publication of the data of the 2017 FRESCO study^[1] is a blessing

Figure 1 Professor Li Jin and Professor Chen Gong spoke online

As a major PI and important participant in FRESCO research, Professor Li Jin explained the important value

From "study design" to "study end" –

Fruquintinib is "safe" and "potent and powerful" tumor control for worldwide benefit

FRESCO-2 is a randomized, double-blind, placebo-controlled phase III RCT study conducted in the United States, Europe, Japan, and Australia ^[2

In terms of study design, the FRESCO-2 study required enrolled patients to have received oxaliplatin, irinotecan, fluorouracil chemotherapy, anti-VEGF or anti-EGFR antibody therapy, and TAS-102 and/or regofinib therapy

Figure 2 Study design

• The primary endpoint of the study was total survival (OS): At the median follow-up of 11.
  3 months, the median OS of patients in the fruquintinib group reached 7.
  4 months, compared with placebo, and the OS of patients was significantly prolonged by 2.
  6 months compared with placebo (HR = 0.
  662, 95% CI: 0.
  549 to 0.
  800; P<0.
  001).
  
  
  

• The secondary endpoint of the study was progression-free survival (PFS): median PFS was 3.
  7 months in the fruquintinib group, significantly longer than in the placebo group by 1.
  9 months (HR = 0.
  321, 95% CI: 0.
  267 to 0.
  386; P<0.
  001).
  
  
  

• Disease control rate (DCR): The DCR was 55.
  5% in the fruquintinib-treated group, significantly higher than the 16.
  1%
  in the control group.
  
  

• OS and PFS benefit subgroup analysis: almost all patients in the subgroup were able to benefit
  significantly from fruquintinib therapy.
  
  

Fig.
3 Benefit of the main endpoints OS and subgroups were studied

Fig.
4 Study the secondary endpoint PFS and subgroup benefit

In terms of safety, the FRESCO-2 study data were similar to those of the FRESCO study, ≥ the incidence of grade 3 adverse events was 62.
7% in the fruquintinib group and 50.
4%
in the placebo group, respectively.

The incidence of adverse reactions between the two groups was similar, and it can be seen that most of the above serious adverse reactions are caused by
the tumor disease itself rather than the therapeutic drug.

Figure 5 Study safety data

Similar survival benefits, greater benefit populations

Compared with the FRESCO study, the survival benefit of patients in the FRESCO-2 study is more precious, and Professor Li Jin compared and analyzed the reasons
in detail.

First, FRESCO-2 has more stringent screening requirements than the FRESCO study, which previously received standardized third-line therapy
including small molecule antiangiogenic drugs such as regofinib.

It is worth noting that the number of people using TAS-102 on the front line of the FRESCO-2 study in the FRESCO-2 study is much higher than the number of people treated with regofinil, and the main reason is that in the European and American populations, regofinil has a relatively high incidence of adverse reactions
.

In the FRESCO-2 study, patients receiving fruquintinib were able to obtain similar benefits of OS and PFS as in the FRESCO study 5 years ago, which shows the strong antitumor activity
of fruquintinib.

Second, it is not difficult to see from the OS and PFS curves published in the study that the curves of the fruquintinib treatment group and the placebo group are separated at the beginning of treatment, and the gap gradually widens with the extension of treatment time in the subsequent follow-up time, which means that the vast majority of patients can benefit from fruquintinib treatment and survive
for a long time.

Third, clinical research in the implementation of the process of strictly grasp the timing of dose reduction and discontinuation of drugs, do their best to ensure that the follow-up of enrolled patients, is the most important guarantee for
the true and effective results of the study.

FRESCO and FRESCO-2 patients were not only extremely close to the benefits of DCR and PFS, but also showed striking similarities in terms of key endpoint OS benefits in patients of different races
and regions.

This aspect reflects the stable and reproducible clinical effect of fruquintinib in patients with advanced CRC
.

On the other hand, it also reflects the rigorous attitude in the execution of clinical studies, which undoubtedly greatly increases the credibility
of related research.

Figure 6 Professor Li Jin concludes his speech

Finally, he talked about the significance of the release of FRESCO-2 research data and the future exploration direction
of fruquintinib.

Professor Li Jin also expressed his views
.

Professor Li Jin gave a high evaluation to the FRESCO-2 research, saying: "The success of FRESCO-2 research is an important foundation for
China's original anti-tumor drugs to go global.

China's independent drug research and development strength has also been fully demonstrated
.

For the future exploration direction of fruquintinib in the field of CRC treatment, Professor Li Jin said that only through more solid scientific research data, further move the treatment indications forward, in order to benefit more patients
with the excellent efficacy of the drug.

At the same time, based on the pre-clinical research of small molecule TKI in the field of combination therapy, it is also expected that China's original anti-tumor drugs will bring the "spring"
of life to patients with advanced CRC.

References:

[1].
Li J, Qin S, Xu RH, et al.
Effect of Fruquintinib vs Placebo on Overall Survival in Patients with Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial.
JAMA.
2018; 319(24):2486-2496.
doi:10.
1001/jama.
2018.
7855.

[2].
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.
ESMO Congress 2022, LBA25.