Immunotherapy, Targeted Agents Transform Lung Cancer Paradigm, But Challenges Remain

Chad Cherington, MD

Immunotherapy and targeted treatments have revolutionized treatment in lung cancer; however, better biomarkers and enhanced efficiency and accuracy of molecular testing are needed to further advance the field, explained Chad Cherington, MD.

Cherington highlighted the game-changing KEYNOTE-189 and CASPIAN immunotherapy trials in non—small cell lung cancer (NSCLC) and extensive-stage small cell lung cancer (SCLC), respectively, as well as the FLAURA trial, which established osimertinib as the frontline standard of care in the frontline setting for patients with EGFR-mutant NSCLC. However, more research is needed to build on these strong foundations, said Cherington.

“[I would like to see future research efforts on] molecular targeting. It is great that we are finding more targets and drug options and now we can treat with more than one targeted drug. We can even treat with a second-line or third-line therapy in some cases,” said Cherington. “The other question involves elderly patients who have a PD-L1 score of less than 50%. We have the option of chemotherapy [for this patient population] but there is a gray area between performance status versus the use of those drugs. It would be nice to have other options earlier on in that situation.”

In an interview during the 2020 OncLive^® State of the Science Summit™ on Lung Cancer, Cherington, a medical oncologist at Ironwood Cancer and Research Centers, discussed groundbreaking developments and critical next steps across the spectrum in lung cancer.

OncLive: What are key advances that have been made recently in lung cancer?

Cherington: Immunotherapy has been the largest change for the vast majority of patients. The second change is within the targeted therapy options. They have been expanding rapidly and every year it feels like there are a few new indications coming out. Another advancement [in the field] came out with a combination of chemotherapy and immunotherapy. KEYNOTE-189 is one of the trials with pembrolizumab (Keytruda) and pemetrexed [being utilized] as a frontline treatment. Also, single-agent pembrolizumab in the first-line metastatic setting, especially for elderly patients with PD-L1 expression greater than 50%, [has been another advancement made].

What are some of the key trials that have been impactful on clinical practice?

Other trials with SCLC, especially extensive SCLC, are the most recent CASPIAN trial and the original IMpower-133 trial. I have already treated several patients with the therapies [used in those trials] and they are good, well-tolerated regimens.

How are you approaching first- and second-line treatment in practice?

The National Comprehensive Cancer Network has a very good guide and a lot of times there are systems that we have to follow. A patient's PD-L1 score and performance status will guide me towards a first-line treatment, whether or not [a patient is categorized as] adenocarcinoma, squamous carcinoma, or SCLC. For second-line treatments for patients who have no molecular markers and who have progressed on immunotherapy, we are looking at single-agent chemotherapy and traditional options.

What are some of the key challenges that you are facing?

One of the key challenges is when you first have a patient with lung cancer, particularly metastatic lung cancer, there is a lot that needs to get done to find the best treatment approach. You have your staging scans, MR brain scans, and then you have your stains of the tissue.

First, getting the biopsy and the time it takes to get the results and then waiting for next-generation sequencing can sometimes take several weeks. Some of these patients cannot wait that long so we have to make our best treatment decisions, put patients on treatment, and then modify treatment when the next-generation sequencing scores come back. That is always a challenge when logistics and timing are involved.

Are there any pressing questions about lung cancer that need answers?

Some questions are when to decide which patients should wait before starting treatment while waiting for their molecular study results to come back. [Another question is] which patients should be treated immediately and receive modified treatment later on and simply knowing which targets are preferred. There are a few clinical trials with drugs that are probably going to be approved in the coming years.

There are also some questions about EGFR in some of the frontline data with the RELAY trial with erlotinib and ramucirumab. This study was being compared with the FLAURA trial with osimertinib. As far as a first-line option, I think most of my colleagues would go with osimertinib.

How are you currently deciding who should receive immediate or delayed treatment?

A lot of it is about how the patient presents in performance status. For example, if they are clinically symptomatic, have a rapidly recurring pleural effusion or symptomatic metastases, then I would be more in favor of trying to expedite workup or maybe admit them to a hospital to expedite workup and administer treatment soon or before I get their testing back.

What is your take-home message?

It takes time to obtain next-generation sequencing data and the approval from insurance and then getting pharmaceutical companies to send the drug to the patient. Each of those steps has the potential for delays and it makes the process cumbersome. However, it is good to have a great staff that stays on top of that and makes sure these [necessary steps] get done.