Should ALK-positive lung cancer get targeted therapy first?

Question

Hello doctor,

I am a 49-year-old lifelong non-smoker recently diagnosed with stage IIIB non-small cell lung adenocarcinoma. My comprehensive genomic profiling shows an ALK rearrangement, PD-L1 expression of 45 percent, and a low tumor mutational burden (3 mutations/MB). My oncologist has advised starting carboplatin and pemetrexed chemotherapy, but I am confused about whether I should receive targeted therapy instead.

I was informed that ALK-positive lung cancers respond well to ALK inhibitors such as Alectinib or Crizotinib, but my insurance is questioning their use as first-line treatment. My CEA level is elevated (65 ng/mL), and my performance status is good (ECOG 0).

I also have a strong family history of cancer (mother with pancreatic cancer, sister with ovarian cancer, and maternal grandmother with breast cancer).

Should I undergo germline genetic testing for BRCA2, TP53, and other hereditary cancer genes?
Will the presence of hereditary mutations affect my treatment plan or prognosis?
Additionally, are there any clinical trials for ALK-positive lung cancer that may offer better outcomes than standard therapy?

Please help.

Thank you.

Answer 1

Hello,

Welcome to icliniq.com.

I read your query.

Based on your diagnosis of stage 3B ALK-positive (stage 3B cancer with anaplastic lymphoma kinase gene rearrangement present) non-small cell lung adenocarcinoma (NSCLC, most common type of lung cancer that grows and spreads more slowly than small cell lung cancer) and your good overall health status, there is an important positive aspect to your case: your tumor has an ALK rearrangement, which is a highly treatable target.

ALK-positive lung cancers usually respond very well to targeted therapies called ALK inhibitors, such as Alectinib or Crizotinib. These medicines are typically preferred over standard chemotherapy (a cancer treatment that uses powerful drugs to kill or slow the growth of cancer cells in the body) as the first line of treatment because they tend to work better, control the disease for a longer time, and cause fewer side effects compared to chemotherapy drugs like Carboplatin and Pemetrexed.

In ALK-positive cancers, markers like PD-L1 (programmed death-ligand 1) and tumor mutational burden are less important, since immunotherapy alone generally does not work as effectively in this specific type of lung cancer.

Given your strong family history of pancreatic, ovarian, and breast cancers, it would also be wise to consider germline genetic testing for genes such as BRCA1 (breast cancer gene 1), BRCA2 (breast cancer gene 2), TP53 (tumor protein 53), and other high-risk cancer genes.

This can help assess inherited cancer risk for you and your family and may guide future cancer screening or eligibility for certain targeted treatments or clinical trials, even though it does not usually change the main ALK-targeted treatment for your lung cancer.

There are also several ongoing clinical trials for ALK-positive NSCLC that are testing newer ALK inhibitors and combination therapies, which may offer additional options now or in the future. Discussing these possibilities with your oncologist could be beneficial.

Overall, by combining your tumor’s molecular profile, your physical fitness, and your family history, your care team can create a highly personalized treatment plan focused on achieving the best possible outcome for you.

I hope this helps.

Kindly revert so I can assist you further.

Thank you.