Better understanding of lung cancer led to plethora of new treatments
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Researchers are learning more about the underpinnings of lung cancer cells that control their growth and spread, according to the American Cancer Society.
Consequently, new targeted therapies as well as immunotherapies have been developed for this patient population. In addition to sunitinib (Sutent, Pfizer), sorafenib (Nexavar, Bayer and Onyx Pharmaceuticals), vandetanib (Caprelsa, Sanofi Genzyme) and cabozantinib (Cometriq/Cabometyx, Exelixis), the FDA recently approved selpercatinib (LOXO-292, Loxo Oncology) for those with RET fusion-positive non-small cell lung cancer and capmatinib (INC280; Incyte, Novartis) for those with advanced NSCLC who harbor MET exon 14 skipping mutations.
Moreover, recent immunotherapy approvals include atezolizumab (Tecentriq, Genentech/Roche) and a combination regimen of nivolumab (Opdivo, Bristol-Myers Squibb) plus ipilimumab (Yervoy, Bristol-Myers Squibb).
“Until recently, all patients with lung cancer were treated with chemotherapy whereas now first-line treatment is almost never chemotherapy alone,” Jacob Sands, MD, oncologist at Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, told Healio. “Targeted therapy is generally the first treatment for those eligible to receive this type of treatment and those without a target but with high PD-L1 expression are given immunotherapy. All other patients are generally treated with combination chemotherapy and immunotherapy.”
Targeted Therapy
The role of targeted therapies in lung cancer is to target and treat specific receptors on cancer cells.
There are seven genomic alterations — EGFR, ALK, ROS1, BRAF V600E, NTRK, MET exon 14, RET — with FDA-approved treatments available, including RET and MET exon 14.
“It is imperative that patients with lung cancers that are non-squamous NSCLC are tested for genomic alterations or mutations/changes in the DNA of the cancer cells and that patients with lung cancer who are never smokers should be tested for genomic alterations,” Sands told Healio. “Specific changes in cancer cell DNA that differ from normal cells can be treated with targeted therapy, as these agents tend to work better compared with chemotherapy and for longer duration.”
Unless a cancer is causing symptoms that requires immediate treatment, genetic testing is imperative prior to starting any treatment, Sands added.
“I often advise patients to undergo testing even if it causes some delay in treatment initiation, because we always want to use the best treatment for a specific patient and not just the fastest treatment,” Sands told Healio.
Immunotherapy
Immunotherapy helps a patient’s immune system attack a cancer.
Cancer cells may avoid being threatened by the body’s immune system by using certain checkpoints that normally keep the immune system in check, according to the American Cancer Society.
A common protein found on the surface of cancer cells, known as PD-L1 helps cancer cells evade the immune system. New immunotherapy agents that block the PD-L1 protein, and/or the corresponding PD-1 protein on T cells, may aid the immune system in recognizing cancer cells and attack them.
“Some of these agents are now approved for use in advanced NSCLC and studies are currently evaluating if giving an immunotherapy drug along with radiation therapy in people who cannot have surgery can improve shrinkage of the tumor and may help patients live longer,” Sands told Healio.
Results from the CheckMate 017 and 057 trials showed nivolumab led to a fivefold improvement in OS at 5 years compared with docetaxel among patients with previously treated advanced NSCLC.
Moreover, among those who were progression free at 2 years, 76% remained progression free at 3 years, 68% remained progression free at 4 years, and 60% remained progression free at 5 years, with 82% of these patients achieving 5-year OS.
The PD-L1 expression test is imperative at the time of diagnosis among patients with lung cancer, Sands added.
“PD-L1 is a receptor on cancer cells that causes the immune system to relax around the tumor cells and when this receptor interaction with the immune system is blocked, it prevents the immune system from relaxing and leads to an attack on tumor cells. We often look for PD-L1 expression to be 50% or more, and among those patients, treatment may include immunotherapy alone or in combination with chemotherapy.”
Two novel immunotherapies have shown promise in certain patients with lung cancer and have recently gained FDA-approval, according to Sands.
“Pembrolizumab has been the approved standard for a while as a single agent but more commonly used as a single agent when PD-L1 expression is 50% or higher and otherwise used in combination with chemotherapy,” Sands told Healio. “In May, the FDA approved atezolizumab for patients with PD-L1 expression of 50% or higher and nivolumab and ipilimumab for patients with PD-L1 expression of 1% or higher. In patients without a targeted therapy option for their lung cancer, immunotherapy has been an extraordinary advance,” Sands told Healio.
Reference:
- American Cancer Society. What’s New in Lung Cancer Research? https://www.cancer.org/cancer/lung-cancer/about/new-research.html. Accessed May 26, 2020.
- Gettinger S, et al. Abstract OA14.04. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 7-10, 2019; Barcelona.
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