[Reporter's View] Why clinical outcomes require deliberation

Even small differences in clinical outcomes can be highly meaningful.

 

Especially for refractory diseases.

 

Recent top‐line results from Compass Therapeutics’ Phase 2/3 COMPANION-002 trial for cholangiocarcinoma have sparked considerable debate within the industry.

 

According to Compass Therapeutics, the treatment of bispecific antibody tovecimig in combination with the cytotoxic agent paclitaxel resulted in the objective response rate (ORR) of 17.1%, which is nearly three times higher than the 5.3% observed with paclitaxel monotherapy.

 

However, some suggested that the 17.1% ORR is considerably lower than the 37.5% ORR recorded in a previous domestic Phase 2 study conducted by Handok.

 

In a domestic Phase 2 trial, tovecimig+paclitaxel combination therapy had a 37.5% ORR.

 

The latest clinical trial's ORR is less than half of the Phase 2 study.

 

It is important to note that it is too early to make a definitive conclusion on the clinical trial outcomes.

 

The patient populations differed significantly, 24 patients in the domestic Phase 2 trial versus 111 patients of varying races and ages in the global Phase 2/3 study.

 

COMPANION-002 trial is still ongoing, and data on secondary endpoints such as progression-free survival (PFS), overall survival (OS), and duration of response (DOR) have yet to mature.

 

Furthermore, the unique characteristics of cholangiocarcinoma must be taken into account.

 

Although the overall patient numbers are relatively small, cholangiocarcinoma is notoriously difficult to diagnose early and is characterized by rapid metastasis and recurrence, leading to a 5-year relative survival rate of only 28.9% (2017–2021).

 

In fact, seven out of ten cholangiocarcinoma patients eventually die.

 

Another primary reason for the low survival rate is ineffective treatment options.

 

In cases of locally advanced or metastatic cholangiocarcinoma where it is inoperable and first-line therapy has failed, there has been no approved targeted therapy available in Korea.

 

Targeted drug studies have been challenging because of early diagnosis and a small population of patients.

 

Although some targeted therapies for cholangiocarcinoma have shown less than a 1-month improvement in PFS compared to placebo, they have surpassed regulatory hurdles.

 

FOLFOX-based regimens yield a median PFS of 4.0 months and an OS of 6.2 months.

 

Some cancer types have many patients and easily detected in early phases.

 

Clinical studies of those types rarely have data recording over ten digits of months of PFS and OS.

 

However, in challenging fields such as cholangiocarcinoma and triple-negative breast cancer, where the development of targeted therapies is complex, even slight numerical differences can be highly significant.

 

Therefore, it would be premature to draw definitive conclusions about Compass Therapeutics' cholangiocarcinoma treatment without waiting for the final data.

 

As the pharmaceutical industry gradually overcomes long-standing challenges in developing effective therapies for cholangiocarcinoma, a range of new treatments is emerging.

 

Recent developments include the addition of immunotherapies such as AstraZeneca's Imfinzi and MSD's Keytruda as first-line options, as well as the emergence of targeted therapies like Pemazyre and Tibsovo for second-line treatment, along with various agents including, tovecimig and rivoceranib.

 

Experts emphasize that, given the scarcity of treatment alternatives for cholangiocarcinoma, even slight differences in efficacy relative to existing therapies can be significant.

 

When interpreting clinical outcomes, it is essential to consider each cancer type's specific clinical context and biological characteristics.

 

Ultimately, understanding the differences in clinical results between cancers with limited treatment options and those with a wide array of available therapies is critical for accurate data interpretation.