Dr Gold on the Benefit of Targeted Therapies in Mutated Lung Cancers

Kathryn A. Gold, MD, medical oncologist, professor, medicine, University of California, San Diego (UCSD), Moores Cancer Center, UCSD Health, discusses the benefit of targeted therapies in patients with mutated lung cancers.

In the lung cancer setting, the application of targeted therapies has been primarily associated with the treatment of patients with metastatic lung cancer, she begins. However, recent data indicate the potential efficacy of these therapies in cases where surgical resection is feasible. The phase 3 ADAURA (NCT02511106) and ALINA (NCT03456076) trials each shed light on the application of targeted therapies in distinct subgroups of patients with metastatic disease.

The ADAURA trial evaluated adjuvant osimertinib (Tagrisso), an EGFR-targeted TKI, in patients with 

-mutant lung cancer who had undergone surgical intervention, Gold explains. In this randomized trial, patients were assigned to receive either osimertinib or a placebo, with a primary end point of disease-free survival (DFS) and a key secondary end point of overall survival (OS), she states. The trial met both end points, demonstrating that osimertinib improved DFS and OS compared with placebo. Consequently, Gold says that in her clinical practice, osimertinib has now emerged as a new standard of care for patients with 

-mutant lung cancer post-surgery, with a recommended 3-year treatment duration.

The ALINA trial enrolled patients with surgically resected 

-positive lung cancer, she continues. The trial sought to determine the efficacy of adjuvant chemotherapy compared with adjuvant alectinib (Alecensa) in this population over a 2-year period, Gold states. Although the full results of the trial, including the OS data, are still pending, preliminary data indicate a DFS improvement with alectinib compared with chemotherapy, she adds.

Overall, both the ADAURA and ALINA trials underscore the potential power of integrating targeted therapies into the early stages of lung cancer treatment, Gold emphasizes. The outcomes of these trials have expanded the understanding of the efficacy of targeted therapies and influenced clinical practices, Gold concludes.

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Kathryn A. Gold, MD, discusses the benefit of targeted therapies in patients with mutated lung cancers.


Kathryn Gold, MD, medical oncologist and professor of medicine at Moores Cancer Center at UC San Diego Health, discusses best practices with the use of sotorasib (Lumakras) in patients with 

 G12C–mutated non–small cell lung cancer (NSCLC).

Despite the availability of sotorasib, chemotherapy and immunotherapy remain the standard frontline options for this patient population, according to Gold. Almost all of these patients should receive a form of immunotherapy, either alone or in combination with chemotherapy, as part of their frontline treatment, Gold says. The selection of immunotherapy should be based on a patient’s PD-L1 expression levels, Gold adds.

If a patient progresses with or without chemotherapy, sotorasib should be considered, Gold says. Several ongoing trials are examining combinations with sotorasib, including pairing the targeted agent with immunotherapy or chemotherapy, to improve response rates. Efforts are also being made to potentially move the agent earlier on in the treatment journey, Gold explains. It remains to be seen which subgroups of patients with NSCLC will benefit most from these approaches, but ongoing studies could potentially provide answers, Gold concludes.

Kathryn Gold, MD, discusses best practices with the use of sotorasib in patients with KRAS G12C–mutated non–small cell lung cancer.

Dr. Gold on Leveraging Sotorasib in KRAS G12C–Mutated NSCLC 

Kathryn A. Gold, MD, associate professor of medicine, University of California, San Diego, discusses the future of osimertinib (Tagrisso) in the treatment of patients with 

Frontline osimertinib is here to stay, says Gold. The agent showed a 19-month progression-free survival, which Gold says is impressive for a very well tolerated drug. Combinations are likely to play a role in the treatment of resistance to osimertinib. The only standard option for patients who progress on osimertinib is cytotoxic chemotherapy, which many patients would like to avoid if possible, says Gold.

Sequencing is less clear following resistance to osimertinib, though clinicians are learning more about resistance mechanisms. Some data suggest that patients who have progressed with a C797S resistance mutation may maintain responsiveness to first- or second-generation agents, at least preclinically.

Clinically, clinicians do not have the data yet. Combination trials are going to be very important in this setting, says Gold. The TATTON trial, for example, is looking at a MET inhibitor in combination with osimertinib. Gold says this combination is looking very promising.

Kathryn A. Gold, MD, associate professor of medicine, University of California, San Diego, discusses the future of osimertinib (Tagrisso) in the treatment of patients with EGFR-mutant lung cancer.

Dr. Gold on the Future of Osimertinib in Lung Cancer

Kathryn A. Gold, MD, medical oncologist, associate professor of medicine, UC San Diego Heath, differentiates carcinogen-induced and virally associated head and neck squamous cell carcinoma (HNSCC).

HNSCC are 2 entirely different diseases, says Gold. HPV-negative squamous cell carcinoma is very different than HPV-positive squamous cell carcinoma, both biologically and clinically. These cancers need to be treated at 2 separated diseases, Gold says, and should not be grouped together solely because they occur in the same area of the body.

In HPV-negative disease, therapy must be intensified to get better outcomes, Gold says. For example, targeting CDK4/6 and other pathways that are possibly involved in cell cycle regulation in the recurrent and metastatic setting has been shown to improve results.

In HPV-positive disease, Gold says that focus needs to be put de-intensifying therapy, which could spare patients from unnecessary toxicities. Immunotherapy may be more important for HPV-positive disease, Gold explains, as there is an opportunity to target pathways such as PI3K. Therapeutic vaccines are another avenue of study in this group.

Kathryn A. Gold, MD, medical oncologist, associate professor of medicine, UC San Diego Heath, differentiates carcinogen-induced and virally associated head and neck squamous cell carcinoma.
 

Dr. Gold on Defining Head and Neck Squamous Cell Carcinoma

Kathryn A. Gold, MD, medical oncologist, associate professor of medicine, UC San Diego Heath, discusses approaching patients with HPV-positive head and neck cancer.

HPV-positive patients tend to have a better prognosis, states Gold. Currently, HPV status is not used as a factor to select treatment options. As research continues, patients may receive less treatment to spare long-term toxicities.

According to Gold, patients who come in with locally advanced disease, can be treated with chemoradiation—which are the vast majority of patients. Chemoradiation of HPV-negative cancer does not have great overall survival; it is only about 40% at 5 years. For HPV-positive cancer&mdash;especially nonsmokers&mdash;85% of those patients are cured.

Dr. Gold on Approaching Patients with HPV-Positive Head and Neck Cancer

Kathryn A. Gold, MD, medical oncologist, associate professor of medicine, UC San Diego Heath, discusses the current state of human papilloma virus (HPV)-related head and neck cancer.

Clinicians are increasingly seeing instances of head and neck cancer that do not have the traditional risk factors.

This is due to the rise in the HPV-related head and neck cancer. These patients tend to have a better prognosis than those with tobacco- or alcohol-related head and neck cancer.

Kathryn A. Gold, MD

Articles

Dr Gold on the Benefit of Targeted Therapies in Mutated Lung Cancers

Dr. Gold on Leveraging Sotorasib in KRAS G12C–Mutated NSCLC

Dr. Gold on the Future of Osimertinib in Lung Cancer

Dr. Gold on Defining Head and Neck Squamous Cell Carcinoma

Dr. Gold on Approaching Patients with HPV-Positive Head and Neck Cancer

Dr. Gold on the Current State of HPV-Related Head and Neck Cancer