Pradnya D. Patil, MD, FACP, Hematology and Medical Oncology fellow, Cleveland Clinic, discusses unmet needs that remain to be addressed with the use of immunotherapy in patients with non–small cell lung cancer (NSCLC).

Identifying biomarkers that can better predict benefit with the use of immunotherapy in NSCLC remains one of the biggest unmet needs in this space, Patil says. Currently, PD-L1 and tumor mutational burden (TMB) are the best biomarkers available for identifying patients who could benefit from immunotherapy. However, these markers are not perfect, Patil notes. For example, there are still instances of patients with very high PD-L1 expression who do not respond to immunotherapy, Patil says. Therefore, in addition to learning more about PD-L1’s and TMB’s roles as a predictive biomarker, identifying other biomarkers from the tumor microenvironment is necessary, Patil says. Tumor infiltrating lymphocytes could represent one novel biomarker, and researchers must better understand what these biomarkers mean, and how to incorporate that information into day-to-day treatment algorithms, Patil emphasizes.

Another area of unmet need remains stems from primary resistance or acquired resistance to immunotherapy. A significant amount of research has already been conducted to better understand mechanisms of resistance; however, it is important to understand how to design clinical trials that will allow clinicians to combat that resistance, Patil notes.

Toxicities associated with immunotherapy are also an area of need for patients with NSCLC, Patil emphasizes. For immunotherapy-based combinations with novel agents, it is necessary to obtain a better understanding of biomarkers to identify patients who are at risk for toxicities and learn how to better manage these toxicities, Patil explains. Although there are national and international guidelines for immune related adverse effects, there's still a bit of variability and not a lot of high level evidence in clinical practice, Patil concludes.

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Pradnya D. Patil, MD, FACP, discusses unmet needs that remain to be addressed with the use of immunotherapy in patients with non–small cell lung cancer.

Dr. Patil on Unmet Needs With the Use of Immunotherapy in NSCLC

Pradnya D. Patil, MD, FACP, Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, discusses the development of KRAS G12C inhibitors in lung cancer.

 mutations were identified in lung cancer decades ago; however, developing a targeted therapy against the RAS pathway has been difficult, Patil explains. Significant research led to the development of the KRAS G12C inhibitors sotorasib (Lumakras) and adagrasib (MRTX849). Sotorasib was approved by the FDA on May 28, 2021, for use as first-line treatment of patients with non–small cell lung cancer whose tumors harbor 

 G12C mutations and who have received at least 1 prior systemic therapy.

Unlike TKIs, KRAS G12C inhibitors are allele specific, which could account for the numerically modest response rates demonstrated by the agents, Patil says. However, these agents offer a novel class of drugs to this specific patient population that has historically been very challenging to treat, Patil concludes. 

Pradnya D. Patil, MD, FACP, discusses the development of KRAS G12C inhibitors in lung cancer.  



Dr. Patil on the Development of KRAS G12C Inhibitors in Lung Cancer 

Pradnya D. Patil, MD, FACP, Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, discusses data from the phase 3 ADAURA trial (NCT02511106) in patients with 

mutated non–small cell lung cancer (NSCLC).

The ADAURA trial yield data that showed an improvement in disease-free survival (DFS) with the addition of osimertinib (Tagrisso) after the completion of adjuvant chemotherapy in patients with completely resected, 

-mutated, nonsquamous NSCLC, according to Patil. Additionally, although the overall survival has not yet been reported, osimertinib is still a feasible option in this setting given the impressive DFS data, Patil says. However, more data are needed to determine if there is an OS benefit with the agent, Patil continues.

Additionally, it is important to consider how to balance toxicities, how to overcome osimertinib resistance, and what additional options are available if a patient develops metastatic disease, Patil says. Overall, the ADAURA trial produced encouraging data for this patient population, Patil concludes.

Pradnya D. Patil, MD, FACP, discusses data from the phase 3 ADAURA trial in patients with EGFR-mutated non–small cell lung cancer.

Dr. Patil on ADAURA Data with Osimertinib in NSCLC

Pradnya D. Patil, MD, FACP, Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, discusses recent developments with targeted therapies in lung cancer.

Targeted therapies have revolutionized the treatment of patients with lung cancer, as these approaches have served to improve survival outcomes and quality of life, Patil says. Previously, non–small cell lung cancer (NSCLC) was treated as a uniform disease, with 1 type of cytotoxic therapy utilized in these patients, Patil adds. Now, NSCLC is understood to be heterogeneous. Therefore, histology and genomic data is now considered to select the appropriate targeted treatment for each patient, Patil notes.

Ongoing research efforts are now focused on developing agents for more difficult targets, and identifying new options for use in the refractory setting following progression on targeted therapies, Patil concludes.

Pradnya D. Patil, MD, FACP, discusses recent developments with targeted therapies in lung cancer.  


Pradnya D. Patil, MD, FACP

Articles

Dr. Patil on Unmet Needs With the Use of Immunotherapy in NSCLC

Dr. Patil on the Development of KRAS G12C Inhibitors in Lung Cancer

Dr. Patil on ADAURA Data with Osimertinib in NSCLC

Dr. Patil on Key Developments With Targeted Therapy in Lung Cancer