How to treat ALK-positive disease with lung cancer?

Question

Hello doctor,

I am 54 years old, and I have been living with stage 4 non-small cell lung cancer (NSCLC) for six years now, which most people, including some doctors, find hard to believe when I tell them. I was diagnosed at 48 with anaplastic lymphoma kinase-positive disease (ALK-positive disease) and started on Alectinib after Crizotinib stopped working around the second year.

My scans have shown stable small lesions in my right lung and one in my liver since then, and my oncologist calls me an exceptional responder, but lately things are changing. My latest computed tomography scan (CT scan) from three weeks ago showed a 6 millimeter growth in the liver lesion, and my carcinoembryonic antigen (CEA) has increased from 4.2 to 11.8 over the last two quarterly tests.

My oncologists are discussing Bigatinib or Lorlatinib as the next options and possibly a repeat biopsy to check for new resistance mutations. I have also developed peripheral neuropathy in my feet, which is becoming worse, and I rate it as 6 out of 10 most mornings.

My cardiologist recently noted a borderline prolonged corrected QT interval (QTc) of 458 milliseconds, which is complicating the choice of next line therapy. I want to understand what my realistic options are and whether there are any clinical trials I should consider, specifically for long-term survivors of ALK-positive non-small cell lung cancer. Does the fact that I have been living with stage 4 non-small cell lung cancer for six years mean that my cancer biology is fundamentally different from others, and does that change which treatments might work?

Please help.

Thank you.

Answer 1

Hello,

Welcome back to icliniq.com.

I understand your concern.

Remarkably, you have been living with stage 4 anaplastic lymphoma kinase-positive non-small cell lung cancer (ALK-positive NSCLC) for six years, which suggests that your cancer biology is more indolent or responsive to targeted therapy than typical cases.

The presence of small and stable lesions in your lung and liver until now indicates that your disease has been well controlled with sequential ALK inhibitors such as Crizotinib and Alectinib, but the recent growth in the liver lesion and the rise in carcinoembryonic antigen (CEA) indicate that the cancer may be developing resistance to Alectinib.

It is also good to note that Brigatinib and Lorlatinib are next-generation ALK inhibitors and can overcome certain resistance mutations; your oncologists may need to take a repeat biopsy to know the exact mutations in order to tailor your therapy. Your condition of peripheral neuropathy and QTc prolongation does make things difficult since some drugs can cause more problems.

Practically, there are several courses of action that you can choose from: you can change to a next generation ALK inhibitor, join the various clinical trials for new ALK inhibitors and combination therapy, or even use local treatment of your liver lesions in some cases through ablation or radiation.

The fact that you have survived longer than other patients with your condition means that your cancer is different and allows for a more personal course of action without rushing into harsher treatment methods.

Maintaining quality of life and managing peripheral neuropathy and heart rhythm risks will be just as important as continuing cancer control.

I hope this helps.

Kindly follow up if you have more concerns.

Thank you.