Weiss Weighs In on Challenges in NSCLC

Jared Weiss, MD

Although significant progress has been made to the treatment landscape for patients with non—small cell lung cancer (NSCLC), challenges remain with varying novel treatment strategies, explains Jared Weiss, MD.

For example, the optimal sequencing of agents remains unsettled, particularly with tyrosine kinase inhibitors for patients with EGFR-mutant or ALK-rearranged NSCLC.

“That is an important question that we are going to have to answer in clinical practice ,” says Weiss.

Other ongoing debates and/or obstacles Weiss addressed include the use of robotic surgery over open approaches, and increasing the use of screening in lung cancer.

OncLive: Can you discuss challenges surrounding TKIs for the frontline treatment of patients with NSCLC?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Advanced Non—Small Cell Lung Cancer, Weiss, an assistant professor, Thoracic Oncology Program, University of North Carolina (UNC)-Chapel Hill, UNC Lineberger Comprehensive Cancer Center, and chair of the meeting, offered his insight on challenges in the field of NSCLC.Weiss: One question I am frequently asked, as newer TKIs are introduced into clinical practice, is, “What will I do next if I use more potent agents first?” In the case of EGFR-mutated NSCLC, we are talking about potentially using osimertinib (Tagrisso) in the frontline setting instead of gefitinib (Iressa), erlotinib (Tarceva), or afatinib (Gilotrif). In the case of ALK-rearranged NSCLC, we are talking about using alectinib (Alecensa) in the frontline setting instead of crizotinib (Xalkori).

Can you speak to the significance of the PACIFIC trial?

The total disease control that a physician expects from an older agent is not superior to the disease control of a newer agent upfront. These newer agents, at least in the case of osimertinib and alectinib, are less toxic than the prior first-line agents. Avoidance of that progression event is beneficial to the patient. For better and for worse, the PACIFIC trial was a very real-world trial. What I mean is there was no mandated PET scans to confirm the stage and no mandated radiation quality control. This is impactful because that is often what the real world looks like. Many patients around the world do not get PET scans and what is treated as stage III is actually stage IV disease. In the real world, we do not have trial-based quality control looking over the shoulder of the radiation oncologist.

The strength is that the PACIFIC trial, in real-world conditions, still showed an improvement of 18 months with the addition of durvalumab (Imfinzi). For those of us who practice in a more idealized setting with PET scans for all patients and strict radiation quality control, as is common practice in the United States, some of us wonder if we can achieve the same benefit that was shown.

If the patients on the PACIFIC trial really had stage IV disease and were randomized to an active drug like durvalumab (Imfinzi) versus placebo, it makes sense that they would respond better to the active drug. It is a similar situation with inadequate radiotherapy. It is a critique that perhaps some of these patients were incurable due to that radiation quality.

Where are we at with screening in lung cancer?

However, this has not stopped my adoption of durvalumab in this practice. It is something that I discuss with 100% of eligible patients. I do not know if it makes the same degree of difference, but it is a massive improvement that optimal practice still demands.Screening is new, so the biggest thing to address is that screening rates are still low in the United States. The National Lung Screening Trial (NLST) demonstrated how big of a difference screening can make, particularly when paired with smoking cessation. That was very striking.

Also, there were very strict limits on who is screened by inclusion criteria. When you look at the society guidelines that are coming out, they are broadening who screening is appropriate for. The society guidelines, while they do not all agree with each other, do make sense.

What is preventing the widespread adoption of robotic techniques for surgical resection?

Finally, there was no drop-off in screening across the 3 years in the NLST. In practice, if a patient is being screened, it should be done annually, not just every 3 years. Additionally, screening should be paired with smoking cessation, which is even more important than the screening itself. Minimally invasive techniques have many elements of superiority over open surgery. However, optimal practice still demands open surgery as it is not clear that robotic surgery is superior to that.