Anastasios (Tassos) Dimou, MD, a medical oncologist at Mayo Clinic, shares advice from managing patients with non—small cell lung cancer (NSCLC) who experience disease progression following therapy.

For patients who progress on therapy, one approach is to rebiopsy, if possible, says Dimou; a tissue biopsy, a liquid biopsy, or both can be used, says Dimou. Several factors should be considered when choosing a patient’s next line of therapy.

First, one must identify whether they are experiencing oligoprogression; in this case, a local approach like radiation and staying the course with the same TKI might be considered.

Another question to contemplate is whether comprehensive retesting with a rebiopsy would identify mechanisms of resistance, and whether that mechanism of resistance is target oncogene dependent or independent, adds Dimou.

Additionally, the question of whether the patients is dealing with progression in the brain or with disease in the brain should also be taken into consideration; in this case, the use of a CNS-penetrant TKI might serve as an effective approach, concludes Dimou.

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Anastasios (Tassos) Dimou, MD, shares advice from managing patients with non–small cell lung cancer who experience disease progression following therapy.

Dr. Dimou on Managing Disease Progression in NSCLC

Anastasios (Tassos) Dimou, MD, a medical oncologist at Mayo Clinic, shares advice from managing patients with non–small cell lung cancer (NSCLC) who experience disease progression following therapy.

For patients who progress on therapy, one approach is to rebiopsy, if possible, says Dimou; a tissue biopsy, a liquid biopsy, or both can be used, says Dimou. Several factors should be considered when choosing a patient’s next line of therapy.

First, one must identify whether they are experiencing oligoprogression; in this case, a local approach like radiation and staying the course with the same TKI might be considered.

Another question to contemplate is whether comprehensive retesting with a rebiopsy would identify mechanisms of resistance, and whether that mechanism of resistance is target oncogene dependent or independent, adds Dimou.

Additionally, the question of whether the patients is dealing with progression in the brain or with disease in the brain should also be taken into consideration; in this case, the use of a CNS-penetrant TKI might serve as an effective approach, concludes Dimou.

Anastasios (Tassos) Dimou, MD, a medical oncologist at Mayo Clinic, discusses emerging treatment options in 

Standard chemotherapy and immunotherapy have demonstrated success in patients with 

Single-agent immunotherapy appears to elicit similar responses for patients with 

-mutant disease as it does for those in the general lung cancer population, says Dimou. Other oncogene-driven lung cancers have not shown similar responses with immunotherapy.

BRAF and MEK inhibitors that are approved in melanoma are also being actively investigated as targeted therapy in 

Although these agents have different safety profiles compared with current regimens, such as the combination of dabrafenib (Tafinlar) and trametinib (Mekinist), they could introduce more options for patients with 

Anastasios (Tassos) Dimou, MD, discusses emerging treatment options in BRAF-positive lung cancer.

Dr. Dimou on Emerging Treatment Options in BRAF+ Lung Cancer

-positive lung cancer.

Standard chemotherapy and immunotherapy have demonstrated success in patients with 

-mutant lung cancer, explains Dimou.

Single-agent immunotherapy appears to elicit similar responses for patients with 

-mutant disease as it does for those in the general lung cancer population, says Dimou. Other oncogene-driven lung cancers have not shown similar responses with immunotherapy.

BRAF and MEK inhibitors that are approved in melanoma are also being actively investigated as targeted therapy in 

-driven lung cancer.

Although these agents have different safety profiles compared with current regimens, such as the combination of dabrafenib (Tafinlar) and trametinib (Mekinist), they could introduce more options for patients with 

Anastasios (Tassos) Dimou, MD, a medical oncologist at Mayo Clinic, discusses the progress made in the treatment of patients with 

Crizotinib (Xalkori) was the first drug to receive FDA approval for use in this patient population, says Dimou. The most recent advances include the newer-generation TKIs, which have all been compared with crizotinib in the first-line treatment of patients with 

Results from the phase III ALEX trial showed that treatment with alectinib (Alecensa) resulted in improved progression-free survival (PFS). Furthermore, brigatinib (Alunbrig) was compared directly with crizotinib in the first-line treatment of this patient population; this drug also led to improved PFS, says Dimou.

The biggest advances over the past couple of years has been the change in the first-line choices that are available, says Dimou; there has been a shift from crizotinib to the newer-generation TKIs such as alectinib and brigatinib. After these agents, lorlatinib or other agents can be used in subsequent lines of therapy, concludes Dimou.

Anastasios (Tassos) Dimou, MD, discusses the progress made in the treatment of patients with ALK-positive lung cancer.

Dr. Dimou on Progress Made in ALK+ Lung Cancer Treatment

Anastasios (Tassos) Dimou, MD, medical oncologist, Mayo Clinic, discusses the limitations of tumor mutational burden (TMB) as a biomarker in lung cancer.

High TMB has been shown to elicit greater response to immune checkpoint inhibitors in multiple tumor types, says Dimou. However, technical and biological limitations associated with TMB have limited its clinical utility as a biomarker in lung cancer.

Technical limitations include variations in targeted gene panel testing, preanalytical tissue fixation, and non-standardized cutoff points, explains Dimou.

Antigen presentation and the ability of the immune system to recognize and eliminate the mutated protein are biological considerations concerning TMB, says Dimou. Largely, these factors depend on human leukocyte antigen (HLA), which is often lost in patients with lung cancer.

Moreover, tumors that have loss of heterozygosity for the HLA result in defects in antigen presentation and therefore are not expected to respond to immune checkpoint inhibitors, concludes Dimou.

Anastasios (Tassos) Dimou, MD, discusses the limitations of tumor mutational burden as a biomarker in lung cancer.



Anastasios (Tassos) Dimou, MD

Articles

Dr. Dimou on Managing Disease Progression in NSCLC

Dr. Dimou on Managing Disease Progression in NSCLC

Dr. Dimou on Emerging Treatment Options in BRAF+ Lung Cancer

Dr. Dimou on Emerging Treatment Options in BRAF+ Lung Cancer

Dr. Dimou on Progress Made in ALK+ Lung Cancer Treatment

Dr. Dimou on Limitations of TMB as a Biomarker in Lung Cancer