Boost in Genomic Testing, Multidisciplinary Input Needed for Personalized Lung Cancer Care

Nagashree Seetharamu, MD, MBBS

Patients with lung cancer should undergo genomic testing at the time of disease progression so that insight can be gained on the genomic transformation of the tumor, according to Nagashree Seetharamu, MD, MBBS, who added that this information, paired with fruitful discussions held with multidisciplinary tumor boards, and awareness of available clinical trials, are all key to providing optimal individualized care.

“[Lung cancer] is a space where we cannot make decisions alone—a group of [experts are needed],” Seetharamu said. “It will take a village to ensure that the patient receive optimal treatment. The best utilization of available resources is [to look] at clinical trials that are available, not just within [your own] institution, but across multiple institutions.”

In an interview with OncLive^® during the 16th Annual New York Lung Cancers Symposium^®, a program hosted by Physicians’ Education Resource^® (PER^®), LLC., Seetharamu, a medical oncologist at Northwell Health, discussed the importance of early and frequent genomic testing in patients with lung cancer, as well as remaining challenges faced in clinical practice and efforts being made to overcome them.

OncLive^®: Could you provide an overview of the case you presented during the New York Lung Cancers Symposium^®?

Seetharamu: The case that I [presented underscores] the importance of rechecking liquid biopsies—particularly at [the time of disease] progression. I [presented] a case of a patient with EGFR-mutated lung cancer who has been on multiple oral TKIs. [For this patient], we [gave] a second-generation [TKI] after a third-generation [TKI], which is unique. [This] does not happen all the time, but there are occasions where a second-generation [TKI] might be effective, and a third-generation drug is not. The [use of] blood-based next-generation sequencing [NGS] was essentially the game changer in this case.

It is very important to first look at the genomic transformation of tumors. [We must also recognize] the importance of molecular tumor boards, which we have at our institution; most other institutions have them, as well. Also, [there is a need for] a multidisciplinary tumor board, where we can discuss options other than just changing the treatments. Finally, [we must also be aware of] the availability of clinical trials within our institutions and across others. We have a great network of New York oncologists, and multiple institutions have partnered with us. [It is valuable to know] what is going on at other institutions. [These are all crucial aspects of the case,] and [it details taking a] patient-centered approach to lung cancer care.

What are the challenges that remain in terms of treating a case like this? Are any efforts being made to overcome them?

This is a unique situation, but many times when patients progress on third-generation TKIs, we really have nothing [to offer them] from a standard-of-care perspective. Chemotherapy has modest activity, immunotherapy typically does not have any activity and there are concerns of increased toxicity, so we resort to clinical trials. Overall, [this area] is a gray zone. Many patients who have done so well on oral TKIs end up at this crossroad, where we are debating what the next step should be.

The challenge is really to figure out the best treatment option for a particular patient. Sometimes we see multiple genomic alterations, and many genomic alterations could happen later. Which one of these is the driver? What should be targeted is always a question. Also, are these drugs compatible? Do we continue the osimertinib [Tagrisso] that the patient has been on, or do we stop that and go to a different line of treatment? These are all unanswered questions. New trials, hopefully, will bring a little bit of clarity on that.

What ongoing research efforts are you most excited about?

So much has been going on in the lung cancer space. I really am looking forward to rapid approvals [of different novel approaches] coming through. Genomic-based medicine is huge, so and is immunotherapy. Combinations with bispecific drugs and trispecific molecules is [likely going to be] the future.

I am looking forward to getting answers on [questions related to] some unmet needs, like central nervous system–directed disease and patient-related outcomes. Those are [areas] that need a little bit more focus, and I hope to see more about them. However, combining targeted therapy with immunotherapy is something that perhaps is going to take the next space.

What is your take-home message that you would like to impart to your colleagues?

It is important to ensure that every patient gets tested. We do not want to leave anyone behind. It is extremely important to get that genomic information. Comprehensive genomic testing is extremely important at diagnosis, and at every step of the way, when there is [disease] progression. If [the testing] is not tissue-based, do a blood-based [approach]. Sometimes combining blood-based with tissue-based [testing] or complementing the 2 is also helpful.

There may be patients who have slow progression, in which case, we may want to continue the same medication. [Other] patients [may] have oligoprogression, where directed treatment toward those sites would be appropriate. There may be patients with overt progression, in which case the blood-based NGS could reveal additional mutations that can be targeted.