“Safe, effective and convenient Zejula for ‘all-comers'"

Interview on Professor Jeong-yeol of gynecology department at Asan Medical Center

Efficacy maintain despite dose control, CBC monitoring “not a problem”

BRCA-negative needs coverage, academia to urge the government

Professor Park Jeong-yeol

Different drugs in a same class can have different indications.

 

It could be a development strategy by pharmaceutical companies or a Columbus’ egg.

 

But clearly, the respective companies would try to appeal for different indications in different prescription area and relevant benefit proven from safety and efficacy data.

 

Two poly ADP-ribose polymerase (PARP)-inhibiting targeted therapies, introduced recently with the heightened anticipation from the ovarian cancer treatment scene, are the examples of the said strategy.

 

Takeda Pharmaceuticals’ Zejula (niraparib), in fact, has been indicated for treating ‘all-comers’ in all approved lines of treatment, regardless of mutation in the targeted BRCA genes.

 

AstraZeneca’s Lynparza (olaparib), approved before Zejula, has a limited indication to only treat ovarian cancer patients with BRCA mutation, except for the second-line treatment.

 

It is not the matter of choosing a superior treatment, but about an option.

 

But having an all-comer targeted therapy is an interesting factor to consider.

 

Daily Pharm interviewed Professor Park Jeong-yeol of gynecology department at Asan Medical Center on the use of PARP inhibitor and Zejula in ovarian cancer treatment.

 

-What are the realistic expectations of medical professionals on Zejula indicated for all-comers in all lines of treatment?

 

Considering the largely unmet medical needs, their expectations are obviously high.

 

Besides as a standard therapy, Zejula could be used as a treatment on all patients diagnosed with ovarian cancer regardless of the line of treatment.

 

In the NOVA study, PARP-inhibiting Zeula confirmed its efficacy in all patient groups regardless of biomarkers statuses like germline BRCA (gBRCA) mutation or homologous recombination deficiency (HRd).

 

The study confirmed the Zejula-treated patient group carrying germline BRCA mutation achieved the median progression-free survival (mPFS) four times longer than that of the control group, and also their risk of disease progression or death was reduced by 74 percent.

 

And Zejula doubled the mPFS in a gBRCA mutation-negative group, and also significantly improved mPFS in a HRd-negative, gBRCA mutation-negative patient group.

 

-Zejula is not the sole option for PARP inhibitor.

 

What would be the reason for treatments with specific targeted gene showing such efficacy?

 

The academia is still discussing which class shows treatment efficacy in all patients.

 

Nevertheless, Zejula is the only proven treatment for all-comers so far, so it would be versatile.

 

-Compared to its competitor Lynparza, Zejula user has to take frequent blood test to confirm hematological adverse reaction.

 

Isn’t it inconvenient for the patients?

 

The complete blood counts (CBC) monitoring is conducted once-weekly for the first month, once-monthly for the next 11 months, and once every two to three months after a year.

 

The ovarian cancer patients generally visit hospital to get a blood test a week after their chemotherapy.

 

Additional treatments would be provided, in case of discovering an adverse reaction in blood test, and the patient has to come in the next week to confirm the status again.

 

So, none of the patients complained of inconvenience in visiting hospitals weekly after administering Zejula.

 

On the contrary, there are more patients satisfied with orally administering Zejula, two to three pills a day.

 

Also from a doctor’s perspective, conducting a weekly CBC monitoring for the first month of administering Zejula does not seem like a problem.

 

-Going back to the NOVA study, the dose of Zejula was controlled depending on the individual tolerance.

 

How do you adjust the dose?

 

For a patient weighing less than 77 kg or showing platelet counts less than 150,000/ μL would start with 200 mg dose, but it would be lowered to 100 mg, if need be, and the administration would be halted for the second reduction of dose.

 

Most of the patients in Korea start the treatment with 200 mg dose.

 

Other patients weighing more than 77 kg and showing platelet counts over 150,000/ μL initiate the therapy with 300 mg, and the dose can go down to 200 mg and 100 mg for first and second reduction, respectively.

 

After reducing the dose down to 100 mg, the administration has to be haltered if the dose needs further reduction.

 

But most of the patients only reduce the dose once.

 

Not many of them actual halt the therapy.

 

In the NOVA study, only 4 percent of the patients exited the therapy due to hematological adverse reaction.

 

Generally, patients lowering the dose down from 200 mg to 100 mg stabilize their adverse reaction and maintain the recovered status.

 

Most of the patients subjectively do not feel the adverse reaction when taking 200 mg.

 

An exploratory data analysis on the NOVA study actually found the efficacy of the treatment was maintained at the optimum dose for individual patients.

 

-The Korean government is conservative about Zejula being effective in patients ‘regardless of BRCA mutation,’ although it has been indicated for all-comers.

 

The clinical evidence demonstrated its efficacy, but the efficacy level differed in HRd-negative patients with BRCA mutation.

 

Would you say the insurance coverage is needed for the all-comer indication?

 

Indeed, it is.

 

Generally, only 15 percent of epithelial ovarian cancer patients have been known to have mutated BRCA 1/2 gene.

 

And it means, 85 percent or the majority of the patients do not express BRCA-mutated gene.

 

So at the moment, the majority of the ovarian cancer patients do not receive coverage on using an effective PARP inhibitor.

 

 The academia is still urging for the coverage.

 

As you may know, Lynparza initially had reimbursement limitation of covering only up to 15 months.

 

The academia raised the voice on it to remove the limitation and they a good end result.

 

Recently, the academia is pressing on the government to grant the insurance benefit regardless of biomarker status.

 

Apparently they have requested the government to expand the current insurance standard.

 

-Have you contemplated on the order of therapies, now that the variety of ovarian cancer treatment including PARP inhibitors and Avastin combination therapy is available?

 

Many of the researchers are also interested in the topic.

 

Currently, there has not been a clinical study head-to-head comparing the efficacy of PARP inhibitor and Avastin (bavacizumab).

 

A real-world research would be possible, when both are approved for the first-line maintenance therapy in ovarian cancer treatment and the related cases are collected.

 

When choosing a medication, adverse reaction from the treatment addressed in a study is considered as crucial as the confirmed efficacy.

 

Moreover, patients’ opinions are definitely a factor to consider.

 

But when it comes down to the order of treatment, using more effective drug seems to be better.

 

All drugs demonstrate better efficacy when used in the first-line treatment.