1 year after Lynparza approved for early-stage breast cancer

Professor Min Hwan Kim of the Department of Oncology at Severance Yonsei Cancer Hospital

Improved survival rate as adjuvant therapy after surgery…reduced a death rate by 32%

No cancer recurrence has been reported yet…favorable level of side effects

“Lynparza demonstrated effects in reducing cancer recurrence“

Professor Min Hwan Kim, Department of Oncology at Severance Yonsei Cancer Hospital.

It’s been over a year since Lynparza was approved for the treatment of early-stage breast cancer.

 

Previously, Lynparza was mainly used for treating metastatic breast cancer, but it expanded its usage following the approval last year for the early-stage treatment.

 

As Lynparza has been confirmed to have a superior drug tolerance in the real-world, experts are advocating its use at early stages to prevent cancer recurrences.

 

During a meeting with Daily Pharm, Professor Min Hwan Kim, Department of Oncology at Severance Yonsei Cancer Hospital, shared an opinion that Lynparza should be used more in early-stage treatments.

 

Recently, targeted cancer therapies have proven their treatment effects at early stages in the field of solid cancer, including lung cancer, breast cancer, and gastric cancer.

 

Lynparza is one of them.

 

Lynparza is a PARP inhibitor-class therapy developed by AstraZeneca.

 

It was approved in 2019 as a treatment for patients with metastatic HER2-negative breast cancer who carry germline BRCA (gBRCA).

 

The PARP1 protein has been known to be overexpressed in female cancers, such as breast cancer and ovarian cancer.

 

Lynparza’s underlying mechanism of action is preventing PARP1 from DNA binding, thereby inhibiting further cancer progression.

 

Previously, patients with metastatic HER2-negative breast cancer and gBRCA mutation had unmet needs in targeted therapy options.

 

Then, PARP inhibitor, which has shown effects in gBRCA metastatic ovarian cancer, emerged as a new treatment option as it demonstrated effects in breast cancer.

 

Furthermore, in February of last year, Lynparza expanded efficacy in treating high-risk patients with metastatic HER2-negative breast cancer and gBRCA mutation.

 

Kim emphasized the use of Lynparza at an early stage to prevent recurrence and for breast cancer patients to return to daily life.

 

Lynparza demonstrated effects in early-stage breast cancer patients gBRCA mutations has been pointed out as the key risk factor for breast cancer.

 

Mutation in gBRCA complicates the DNA damage repairs.

 

In this case, genetic changes in a normal cell can lead to cancer occurrence.

 

Mutations in gBRCA are found in around 5-10% of the total breast cancer.

 

Whereas the average age of diagnosis for breast cancer is 63, the average age of diagnosis is relatively early when there is a BRCA1 mutation, at an average of 44.1, and a BRCA2 mutation, at 45.1.

 

Breast cancer patients with gBRCA mutations confer poor prognosis, and as for HER2-negative breast cancer, there is no targeted receptor, which puts patients in limited treatment circumstances.

 

But a relief for such individuals suffering from this condition is that PARP inhibitors, which have been found effective in treating breast cancer with gBRCA mutations, are now available.

 

Lynparza, in particular, is expanding its presence after having demonstrated its effectiveness in the Phase 3 OlmpiA clinical trial, which involved HER2-negative breast cancer patients at early stages who carry gBRCA1/2 mutations.

 

The clinical trial involved 1,836 patients who have completed adjuvant chemotherapy either prior to or after the surgery.

 

During the follow-up period of 3.5 years (median value), post-surgical Lynparza adjuvant therapy reduced breast cancer recurrence or risk of death by 42% compared to placebo.

 

Lynparza group’s invasive disease-free survival (IDFS) at 4 years was 82.7%, which was 75.4% longer than the placebo, and their distant disease-free survival (DDFS) was 86.5%, showing a significant improvement compared to 79.1% in the placebo group.

 

For this reason, Kim strongly voiced his opinion towards the use of anti-cancer agents, such as Lynparza, at early stages of cancer.

 

When cancer relapses, complete recovery cannot be anticipated, and improvements in survival rate are rarely found.

 

Kim said, “When cancer relapses, even if Lynparza is used, complete recovery cannot be expected, and improvements in overall survival rate have not been demonstrated.

 

Therefore, the benefit of using PARP inhibitors at early stages is enormous.

 

Lynparza demonstrated overall survival rate improvements at early stages of HER2-negative breast cancer, increased complete recovery rate, and has solid clinical evidence.” He also emphasized that the “Lynparza group’s distant disease-free survival (DDFS) at four years was 86.5%, which practically lowered the recurrence rate to one-third.

 

The clinical trial involved patients with triple-negative breast cancer, in which case cancer recurrence carries a higher risk of death.

 

Reducing the cancer recurrence for these patients means a lot since it provides life-extension.” Non-reimbursed gBRCA screening…breast cancer patients face greater burden After receiving approval for expanded indications in early-stage breast cancer last year, Lynparza prescriptions are now available for patients.

 

The basis for approval was superior drug tolerance and low side effects in early-stage breast cancer.

 

Kim said, “To date, there have been no patients with cancer recurrence after Lynparza use.

 

We are experiencing that Lynparza proved superior drug tolerance in treatment settings.

 

We initially had concerns about the potential blood diseases, such as leukemia, considering the PARP inhibitor’s characteristics, but the side effects have been generally favorable when prescribed.

 

Additionally, there weren’t many cases of anemia and tiredness.” Until now, the majority of targeted cancer therapies have been administered as non-reimbursed despite being approved for early-stage treatment options in various cancer types.

 

Lynparza is non-reimbursed for use as post-surgical adjuvant therapy.

 

Therefore, Kim emphasizes that early-stage cancers should be treated with targeted therapies more.

 

“Considering the overall medical costs, early-stage treatment is more beneficial.

 

The initial treatment costs about KRW 20 million to 30 million per year.

 

Such treatment lasts about two years, and costs continue to grow when treating beyond the period,” Kim said.

 

“Therefore, in terms of the society, it is important to prevent recurrence and save costs afterward through early-stage treatments,” he added.

 

Kim also emphasized the importance of setting reimbursement criteria for the cost of gBRCA gene screening.

 

Currently, breast cancer patients carrying gBRCA mutations bear a greater burden due to non-reimbursed administration and the cost of gene screening.

 

The current reimbursement criteria for gBRCA screening include △At least one family member or relative (up to third-degree relative) with breast cancer, ovarian cancer, male breast cancer, metastatic prostate cancer, or pancreatic cancer △Been diagnosed with breast cancer at age 40 or younger △Been diagnosed with triple-negative breast cancer, bilateral breast cancer, or breast cancer with concurrent ovarian or pancreatic cancer at age 60 or younger △Male breast cancer and ovarian cancer patients.

 

Kim said, “gBRCA gene screening costs about KRW 20 million when reimbursed, which burdens patients to have it tested without reimbursement coverage.

 

Screening is advised in the United States for those with triple-negative breast cancer, regardless of age.

 

However, Korea’s reimbursement coverage is narrow, leading to missed cases of diagnosing patients with gene mutations.” And added, “Since mutations in gBRCA are found about 10% in patients with hormone-positive breast cancer, we have a higher possibility of missing the detection because they are excluded from the reimbursement coverage for screening.” “Because the breast cancer occurrence rate is high in Korea, and it can be higher, appropriate treatment is critical.

 

In particular, patients’ access to innovative new drugs should be improved,” Kim commented.

 

“In Korea, there are cases of providing patient accessibility by granting selective reimbursement when new cancer drugs are not reimbursed, but almost half of the patients give up on the treatment because of the costs.

 

Therefore, we need a more flexible system,” Kim emphasized.