Socinski Says Immunotherapy, Targeted Therapy Have Altered Outlook in NSCLC

Brandon Scalea
Published: Monday, Jan 28, 2019

Mark A. Socinski, MD
Mark A. Socinski, MD
An elevated understanding of the biology of lung cancer has allowed researchers to develop highly effective immunotherapy regimens and targeted agents, said Mark A. Socinski, MD.

Based on positive data from 3 pivotal studies evaluating the use of pembrolizumab (Keytruda) in the frontline setting in patients with non–small cell lung cancer (NSCLC), 2018 was a big year for this space. The PD-1 inhibitor has been approved by the FDA for use as a single agent and in combination with traditional chemotherapy regimens across squamous and nonsquamous histologies.

Practice-changing data with immunotherapy have also made their way into stage III disease. As a result of the phase III PACIFIC trial, the FDA approved the use of durvalumab (Imfinzi) in the treatment of patients with locally advanced, unresectable stage III NSCLC who have not progressed following chemoradiotherapy in February 2018.

Results showed a significant advantage in progression-free survival (PFS) with the immunotherapy agent; the median PFS was 17.2 months in the durvalumab arm versus 5.6 months in the placebo arm. Updated data showed that the 2-year overall survival (OS) rate in those who were given durvalumab was 66.3% compared with 55.6% for patients who received placebo.

However, acquired resistance to some of these novel regimens still poise a significant challenge, Socinski explained.

In an interview with OncLive at the 16th Annual Winter Lung Cancer ConferenceTM, Socinski, the executive medical director at AdventHealth Medical Group, provided an overview of the current landscape for lung cancer treatment and highlighted where much-needed work still remains.

OncLive: How has the outlook for patients with lung cancer changed in recent years?

Socinski: The outlook is much better assuming you utilize what I consider to be the standard of care today. In terms of stage IV disease, you need to define the molecular nature of the disease. Many of the lung cancers that we see have molecular drivers, and we have a growing list of oral targeted therapies. The other issue is the implementation of immunotherapy in accordance with PD-L1 testing. Given the expansion of the knowledge we have regarding the basic biology of the disease, we have figured out that we should be testing for mutations like EGFR, ROS1, and BRAF at the very least, but also for RET translocations, MET alterations, and HER2 [mutations]. Comprehensive genomic testing identifies patients who have targets that we can treat with therapy that is known to work better than standard chemotherapy in many situations.

The biggest thing that we have accomplished in the last year or so has been bringing immunotherapy—which was typically used in the second-line setting—into the frontline regimens that are standard both in squamous and nonsquamous disease. We have seen real benefit in these patients. The outlook and prognosis for patients has rapidly improved over the last few years, based on the molecular observations as well as the incorporation of immunotherapy.

How does the advent of novel treatment approaches affect some of the more conventional modalities, such as radiation therapy?

It is still all about the basics. There are 2 things we have to get absolutely right. First is the diagnosis, which, in 2019, includes accurately knowing the histology as well as the molecular status—particularly in stage IV disease. The second thing we have to get right is the stage. If you define stage I, then that is the surgical stage; stage II is also surgical disease. Stage III is mostly chemotherapy and radiation; that has not changed.

However, we now incorporate immunotherapy following the completion of radiation because we know it can lead to a survival advantage. Diagnosis and stage are very important because they inform the treatment approach for each patient.

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