“Lynparza now available for unmet medical needs in TNBC"

Considering prescribing the treatment to BRCA-mutated patients first, reimbursement needed

Too early to call class effect on PARP inhibitors

Professor Sohn Joohyuk

“Breast cancer has various treatment options.” True, but not always for all types of breast cancer.

 

Since the release of Herceptin (trastuzumab), human epidermal growth factor receptor 2-positive (HER2+) breast cancer treatment paradigm has been shifted and follow-on targeted therapies are continuing to enter the market.

 

The launch of Ibrance (palbociclib) has also brought new approach to hormone receptor positive (HR+) and HER2- breast cancer treatment scene.

 

However, triple-negative breast cancer (TNBC), negative in all receptors including estrogen, progesterone and HER2, still has treatment needs unmet.

 

For a long time, chemotherapy has been the only treatment option for TNBC.

 

Although Roche’s targeted therapy Avastin (bevacizumab) has won the indication to treat TNBC for the first time in Korea, the treatment has not been listed for reimbursement, yet.

 

And recently a targeted therapy option was introduced to the TNBC treatment market.

 

AstraZeneca’s Lynparza (olaparib), first indicated to treat patients with ovarian cancer, has released tablet form and expanded its indication.

 

Poly ADP ribose polymerase (PARP) inhibitor Lynparza has heightened the anticipation among patients with gBRCA-mutated TNBC, who have been treated with chemotherapy.

 

Daily Pharm interviewed Professor Sohn Joohyuk of Medical Oncology Division at Severance Hospital about the effect of Lynparza.

 

-What would be the reason behind sluggish development of TNBC treatment?

 

Disease with clear biomarker has treatments developed accordingly, and also developing a treatment requires predictable marketability.

 

70 percent of breast cancer patients are HR+ patients, and 15 percent of breast cancer is HER2+.

 

But TNBC patients only take up 15 percent of all breast cancer types.

 

And even if a patient is categorized to have TNBC based on diagnosis of exclusion, they could be categorized again into various subtypes.

 

With such diversity in breast cancer types, developing a treatment was surely challenging.

 

But as most of breast cancer treatments these days are in development focusing on TNBC, we could expect to see more of new and promising findings in the future.

 

-In the OlympiAD study, Lynparza-treated patient group demonstrated median progression-free survival (mPFS) of 7.0 months.

 

It is arguable the difference against chemotherapy group with 4.2 months was barely noticeable, which proves the point the treatment for TNBC patient is highly difficult.

 

Despite all, could we say the release of Lynparza is remarkable?

 

It is apparent that TNBC itself is quite aggressive and expecting as effective treatment as HR and HER2+ treatment is not so easy due to diverse types of the cancer.

 

The second-line therapy, after failing first-line therapy through existing anthracycline and taxane options, was limited to chemotherapy to treat TNBC.

 

And because it was so limited that the median overall survival was at around one to 1.5 years.

 

On the other hand, Lynparza has demonstrated significantly longer PFS in OlympiAD study, and response rate was also higher.

 

From clinical point of view, high response rate is always considered crucial factor of consideration, so Lynparza can be viewed as a good option.

 

-Based on the said clinical findings, Lynparza entered the market technically as a second-line treatment.

 

Do you think it has the potential to become a first-line PARP inhibitor option?

 

Sure.

 

OlympiAD trial was designed to test on patients, who have been previously treated with anthracycline and taxane.

 

The study combined patients taking first, second and third-line therapies.

 

-Recently, immunotherapy Tecentriq (atezolizumab) has been approved as a fist-line therapy in combination with paclitaxel.

 

As for a healthcare provider, now you are given two options.

 

How would you utilize the options?

 

For a patient diagnosed with BRCA mutation, I would first use PARP inhibitor on the patient who has been treated with anthracycline and taxane, as a supplementary therapy prior to a surgery.

 

And because doctors have not reached a consensus on prescribing either immunotherapy or PARP inhibitor for TNBC patients, the effective treatment for respective patient could differ case by case.

 

-If PD-L1 is expressed and BRCA is mutated simultaneously, would it possible to combine immunotherapy plus PARP inhibitor plus chemotherapy?

 

At the moment, immunotherapy plus PARP inhibitor combination has an ongoing clinical study, but triple combination has not started a clinical study so it is not easy to say.

 

-PARP inhibitor products in same class are launched one after another.

 

Are there differences between those products?

 

The reported clinical data between Lynparza and Talzenna (talazoparib) were not too far off.

 

Their efficacy and safety profile could be considered on par.

 

A candidate medicine, 'ABT-888' has unveiled meaningful clinical findings.

 

But it is too early to talk about actually using the medicine at this point.

 

Only because they are in a same class, it is not to say there is no difference.

 

But the clinical data disclosed so far showed similar level of effect between Lynparza and talazoparib.

 

-Do you agree Lynparza needs reimbursed prescription?

 

The patients and doctors’ needs for Lynparza-like treatments have been unmet, and patients with TNBC lacked a good treatment option so far.

 

To improve access to Lynparza, we need to both list the drug for reimbursement and improve access to BRCA mutation test.

 

-Lastly, would you like to give us an advice on enhancing breast cancer treatment environment in Korea?

 

To say the least, the current treatment environment has gotten much better.

 

But it would be still helpful to build a better treatment environment by reflecting specialists’ opinions on apparent grey areas.

 

For instance, there is a debate over the timing of using Herceptin, Kadcyla (trastuzumab emtansine), Perjeta (pertuzumab), and docetaxel.

 

The mentioned drugs could be used after a year since the surgery as a supplementary therapy.

 

While using trastuzumab, it is difficult to use TPH when the condition relapses or any other emergency occurs.

 

And sometimes taxane has to be prescribed inevitably to use Kadcyla.

 

More flexible reimbursement listing is needed to appropriate use available options.

 

Although Korea has a wider choice of reimbursed options than in other Asian countries, the country lacks flexibility in listing reimbursement.