Select the right initial treatment for kidney cancer

Immuno-Targeted therapy combo is the trend in kidney cancer

[Interview] Dr. Chan Kim, Professor at CHA Bundang Medical Center (Medical Oncology/Hematology)

Keytruda+Inlyta response rate twice longer than SoC…Lenvima combo also shows promise

Many not be able to use cancer immunotherapies if patients used other anticancer drugs first… need to careful decided on first-line therapy

Cancer immunotherapies are receiving the spotlight in the treatment of kidney cancer.

 

Demonstrating superiority over existing therapies, these drugs are quickly gaining ground in the field of kidney cancer treatment.

 

Recently, MSD’s cancer immunotherapy ‘Keytruda (pembrolizumab) received approval as first-line treatment in combination with Inlyta(axitinib).

 

Afterward, the immuno+immunotherapy combo ‘Opdivo (nivolumab)+ Yervoy (ipilimumab)’ also received approval as a first-line treatment option.

 

Dr.

 

Chan Kim, Professor of Medical Oncology/Hematology at CHA Bundang Medical Center believes that the use of cancer immunotherapies will broaden in the field of kidney cancer.

 

And there’s ample grounds to support Kim’s belief.

 

Keytruda in combination with a different targeted therapy, ‘Lenvima (Lenvatinib)’ has recently produced even more superior data in a clinical trial.

 

However, limitations do exist.

 

Currently, cancer immunotherapies are approved only for the first-line indication.

 

Therefore, if the patient had previously used other treatments, they may not be prescribed cancer immunotherapy drugs.

 

Therefore, patients with Stage IV kidney cancer must carefully consider and select their first treatment.

 

Dailypharm met with Professor Kim to seek his insight on the significance and prospect of cancer immunotherapy drugs in the field of kidney cancer.

 

Professor Chan Kim

-How has the kidney cancer treatment environment changed with the introduction of cancer immunotherapies? = Kidney cancer is a field known for its poor response to general chemotherapy or radiotherapy treatment.

 

Due to this, cytokine-based immunotherapy has been used as an option for over 20-30 years in the field, but even this option has not been broadly used because its objective response rate is only around 10-20%, with serious side effects.

 

This treatment paradigm for kidney cancer has completely changed with the introduction of cancer immunotherapy drugs (immune checkpoint inhibitors).

 

Cancer immunotherapy drugs have fewer side effects than previous drugs and can be used safely even in elderly patients.

 

Most of all, it showed a good therapeutic effect.

 

However, immunotherapy drugs by themselves were not enough to produce satisfactory results as the objective treatment response rate of immunotherapy drugs alone was around 25-30%.

 

As a result, attempts to use immunotherapies in combination with targeted therapies have been made, and clinical studies on this combination were released for kidney cancer in 2019.

 

Results showed that the immuno+targeted therapy combination achieved a twice higher ORR than monotherapy, with an ORR of 55-60%.

 

The uncrossed barrier of 30% was finally overcome.

 

-Were many combination therapies implemented in practice after the data was presented on the immuno+targeted therapy combination?

 

How effective is it in practice? =Use of the combination increased explosively after the presentation.

 

In Korea, Keytruda in combination with the targeted therapy Inlyta is most commonly used.

 

Much treatment data has been accumulated on the combination since its introduction in September 2019.

 

Our hospital presented data on 42 kidney cancer patients who were treated with the Keytruda+Inlyta combination from September 2019 to March 2021 at the 47th Annual Meeting of the Korean Cancer Association that was held from the 17th to 18th this month.

 

One key thing to note is that at the data cut-off point (June 3rd, 2021), the ORR was 54.3%, an excellent rate that is comparable to the clinical trial results.

 

Also, among the patients, 2.9% achieved a complete response and 51.4% achieved a partial response.

 

The median progression-free survival was 12.4 months, and the median OS was not reached in our study.

 

In particular, tumor size in patients with aggressive tumors whose symptoms are difficult to control reduced significantly.

 

85% of the patients survived, and 63% are still continuing their treatment with the combination therapy.

 

The 1-year survival rate is expected to be around the 90% range.

 

In general, Real World Data (RWD) often does not produce as good a result as clinical trials that were conducted in controlled environments.

 

In this context, the fact our results in the field showed a 90% survival rate that is similar to the clinical trial is encouraging news.

 

-How would you interpret the 42 month long-term follow-up data on Keytruda+Inlyta that was recently presented in the 2021 ASCO Annual meeting? =The academic society had been unsure whether the combination would work in the long-term The data that was presented at the ASCO meeting holds significance as it demonstrated the long-term effect of Keytruda+Inlyta.

 

More specifically, in the KEYNOTE-426 study, the overall survival of the combination therapy was 45.7 months, significantly longer than the 40.1 months when using the standard treatment, ‘Sutent (sunitinib).’ PFS also showed a significant difference of 14.7 months vs 11.1 months.

 

OS at month 42 was 57.5% vs.

 

48.5%, respectively, and PFS at the same period was 25.1% vs.

 

10.6%, for the combination therapy group and Sutent group.

 

ORR was 60.4% for the combination therapy and 39.6% for sunitinib.

 

CR was also higher in the combination therapy group, being near 10%, compared to the 3.5% of sunitinib.

 

-The Keytruda+Inlyta combination is currently approved only as a first-line treatment.

 

Does this mean patients who already used other drugs do not have the chance to use the combination?

 

=Yes.

 

Patients often visit our hospital wanting to use Keytruda after using targeted therapies for a month or so.

 

It is unfortunate, but these patients are not allowed to use Keytruda because it is only approved as first-line in Korea.

 

This is why selecting the right initial treatment is ever so important for stage IV kidney cancer patients.

 

If you hastily decide on using a treatment, it is highly likely that you may miss a good opportunity, so I ask the patients to make an informed decision after carefully collecting ample information in advance.

 

-Recently, the Keytruda+Lenvima combination had also shown excellent, differentiated data results from previous kidney cancer treatments.

 

=We have high expectations for the Keytruda+Lenvima combination.

 

In the Phase III CLEAR study, the combination showed a median PFS of 23.9 months, which is over twice longer than the PFS shown in the Sutent group’s 9.2 months.

 

The risk of mortality also decreased by 34% compared to the Sutent group.

 

ORR of the combination therapy was 71%, and 16.1% of the patients reached complete response.

 

The combination is expected to address all the limitations in effect and side effects that arose from previous treatments.

 

If this combination is also approved in the future, 4 treatment options (targeted therapy, immuno+immuno combination therapy, Keytruda+Inlyta, Keytruda+Lenvima) will become the established options used to treat kidney cancer.

 

Among these, the Keytruda + Lenvima combination is expected to be the most anticipated option in the field.

 

-What role would cancer immunotherapies play in the field of kidney cancer in the future?

 

=Cancer immunotherapies are already a well-established treatment option in kidney cancer, and its use will continue to expand in the future.

 

I believe the new treatment trend would be for low-risk groups to first use targeted anticancer therapies and for mid-to high-risk groups to consider the use of immuno+targeted combination therapies.

 

As the combination is yet non-reimbursed, not enough patients are benefiting from this effective treatment option.

 

I hope the government will provide support as soon as possible in consideration of its excellent treatment effect.