Tecentriq fails urothelial carcinoma trial but beneficial

CPAC decides to recognize its benefit in Korea

Roche voluntarily withdrew UC indication from the FDA last year... indication still valid in Korea

Although the conditional clinical trial failed for Roche’s cancer immunotherapy ‘Tecentriq,’ experts in Korea decided to recognize Tecentriq’s benefit for ‘patients with locally advanced or metastatic urothelial carcinoma who are not eligible for platinum-based chemotherapy’ and maintain the indication as it is unethical to reorder clinical trials when these patients have no other alternatives.

 

According to the minutes of the Central Pharmaceutical Affairs Council meeting that was held on November 28th last year which was recently disclosed by the Ministry of Food and Drug Safety, the CPAC members decided to recognize the benefit of the therapeutic confirmatory clinical trial results on Tecentriq.

 

At the time, Roche’s subsidiary Genentech had voluntarily withdrawn Tecentriq’s indication in the US for the treatment of adults with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.

 

In the US, Roche had first acquired Tecentriq’s bladder cancer indication through the Accelerated Approval Program under the condition of conducting a confirmatory trial, then conducted a Phase III IMvigor130 trial to evaluate Tecentriq plus platinum-based chemotherapy for the first-line treatment of people with previously untreated advanced bladder cancer.

 

However, as the designated postmarketing requirement (PMR) did not meet the primary endpoint of overall survival (OS) for Tecentriq plus chemotherapy compared with chemotherapy alone, the company had withdrawn the indication.

 

In 2017, Tecentriq was conditionally approved for the ‘treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 tumor proportion score of at least 5%,’ under the condition that it conducts a therapeutic confirmatory trial to demonstrate superiority over chemotherapy in urothelial carcinoma.

 

The MFDS asked the CPAC to “determine whether the indication should be maintained despite the recent results in the current situation where treatment options have not changed much for urothelial carcinoma since 2017.” To the request, one CPAC member said, “Tecentiq showed an improvement over chemotherapy in some of the efficacy endpoints such as DOR in ITT or PD-L1 positive patients.

 

Therefore, we need to maintain the approval status to offer options to such patients.” The member's opinion was that not many options exist for patients who cannot use platinum-based chemotherapy and that it is better to maintain approval, even if it is a conditional one if the results show a similar level of effect to chemotherapy.

 

Another member said, “Based on the trial, Tecentriq’s combined use with chemotherapy should be excluded, and the indication for patients who are not eligible for platinum-based chemotherapy should be maintained as they have no other options.

 

Therefore, what we need to decide is whether to maintain the indication for patients that can use carboplatin.” The committee chair added the opinion that the company should reconduct the clinical trial in principle.

 

The CPAC chair said, “In principle, the company should conduct the trial again.

 

What matters most is the therapeutic efficacy, so we need to decide whether it is appropriate to allow Tecentriq’s use in all situations and options.” Also, an opinion that it would be better to maintain the indication for patients without options was raised, pointing to how it would not be appropriate to create a situation where the committee's conclusion deprives patients of the only option they may have.

 

The chair concluded, “Although Tecentriq failed the confirmatory trial in urothelial carcinoma, we conclude that we acknowledge the benefits of the drug as it is unethical to order the company to reconduct a clinical trial when patients with locally advanced or metastatic urothelial carcinoma who are not eligible for platinum-based chemotherapy have no other alternatives.” Meanwhile, Roche Korea is known to be discussing whether to maintain Tecentriq’s urothelial carcinoma indication in Korea, with regards to the voluntary withdrawal of the urothelial carcinoma indication in the US.