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NSCLC Treatment Paradigm
Expert View on the Evolving Treatment Paradigm in Advanced NSCLC

Released: June 23, 2020

Expiration: June 22, 2021

Matthew Gubens
Matthew Gubens, MD, MS
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Palliative Care

In our clinic, patients who are treated with targeted agents or immunotherapies are also seen by palliative care (also known as symptom management care) specialists as part of their care team. This is an important part of their management because of the unusual toxicity profiles of these agents.

There is evidence supporting the role of palliative care in this setting. A study was conducted of patients with metastatic NSCLC who were randomized to receive early palliative care or standard oncologic care alone, then quality-of-life measures were assessed at baseline and 12 weeks using the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale, respectively.98 Results showed that early palliative care significantly improved both quality of life, with a mean FACT-L score of 98.0 vs 91.5 (P = .03), and mood (depressive symptoms seen in 16% vs 38%, respectively; P = .001). Even the median OS was longer with early palliative care, at 11.6 months vs 8.9 months with standard care (P = .002).

In our clinic, symptom management or palliative care definitely has a frequent role starting early in the course of disease.

Summary

In summary, there has been tremendous progress in NSCLC treatment over the past several years. In the class of targeted therapy, inhibitors of EGFR, ALK, and ROS1 have led the way, with the development of second-generation and third-generation drugs that can better overcome the blood–brain barrier with improved toxicity profiles. The FDA has now approved targeted inhibitors of BRAF, NTRK, RET, and MET. There is also great promise emerging for targeting other pieces of the NSCLC pie including KRAS and others. The key take-home message here is that you cannot treat a gene mutation or a fusion that is not recognized on molecular profiling. As the number of targets increases, the cost effectiveness and appropriateness of broad molecular testing from the beginning becomes greater.

Looking forward, as we treat more patients with targeted therapies it will be important to learn more about how resistance evolves, and to develop precision strategies for treating the specific evolutionary events in a patient’s cancer history. Repeat biopsies will be important here, either by needle or liquid biopsy.

Immunotherapy has also been a story of tremendous progress in NSCLC treatment. At this point, for most patients in the first-line setting, a combination of immunotherapy and chemotherapy is an appropriate choice and 1 that clearly improves outcomes over chemotherapy alone. The clear exception is when a first-line targeted therapy is available, in part because it is likely to be more effective and more durable, but also because the immunotherapy has the potential to interact with the targeted therapy in a deleterious way. Single-agent pembrolizumab is reasonable for a subset of patients with high PD-L1 expression, who must be chosen appropriately. Bevacizumab may be a useful adjunct, as shown by IMpower150. However, it is not yet approved for use with any pemetrexed-based combinations, which is the treatment of choice for nonsquamous NSCLC. It also is not approved for squamous disease.

Looking forward, we will be learning more about the role of immunotherapy combinations in NSCLC as we gain experience with different checkpoints and other targets within the immune system. The combination of nivolumab and ipilimumab was recently approved by the FDA and is being evaluated in several clinical trials along with countless others. We also have to learn more about immunoresistance, including how to best use combinations and other strategies when immunotherapy alone is ineffective.

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