Best Management Practices for a Patient With Early-Stage Non-Small Cell Lung Cancer

Lyudmila Bazhenova, MD, Moores Cancer Center, University of California, San Diego, California, discusses the course of treatment she would take for a patient with early-stage non-small cell lung cancer (NSCLC). 

Based on results from the phase 3 ALINA trial, Dr Bazhenova stated, “my approach in those patients has been chemotherapy followed by alectinib in those patients who are interested in chemotherapy and are able to tolerate chemotherapy. If your patient is not interested in chemotherapy or you do not think that chemotherapy is going to be tolerated by the patient, then alectinib by itself is a reasonable option."

Transcript: 

Hi, I'm Dr Lyudmila Bazhenova, thoracic medical oncologist and professor of medicine at The University of California San Diego. For the case that was presented above, my choice of treatment would be chemotherapy followed by alectinib. For any patients who underwent surgery and now we are making a decision on the role of adjuvant therapy, we pretty much have 3 options: we can do chemotherapy, we can do immunotherapy, and we can also do targeted therapy for 2 patient populations specifically: one is an EGFR mutation and the second is an ALK mutation.

Immunotherapy is generally not recommended for patients with ALK fusion. Patients with ALK fusions were allowed in the IMpower010 trial however, there were only 43 patients with ALK rearrangement and when you look at the hazard ratio for this patient population it was 1. Patients with ALK rearrangements were also allowed in the PROS trial, which is another adjuvant trial for immunotherapy, but only 14 patients were enrolled and the efficacy of immunotherapy in this cohort was not reported. We have evidence that in stage 4 disease immunotherapy is not an effective therapy for ALK-rearranged lung cancer and that is the main reason why I'm not even considering adjuvant immunotherapy for this patient population. 

We know that chemotherapy increases cure rate for patients with resected lung cancer, that has been established over a decade ago, and increases in survival ranges from about 5% to 10% so chemotherapy is certainly a consideration for this patient. The main discovery of recent is the efficacy of adjuvant alectinib in patients with resected lung cancer who happened to have an ALK fusion and this was based on ALINA trial. 

ALINA was a phase 3, open-label, randomized clinical trial who took patients with stage 1b, specifically tumors more than 4 centimeters, stage 2/3a lung cancer. Patients would have completed surgical resection and then they were randomly assigned to alectinib or chemotherapy. The chemotherapy choices were pretty standard: cisplatin plus vinorelbine, gemcitabine, or pemetrexed. The duration of alectinib therapy was 24 months. The primary end point of the study was disease-free survival (DFS) with hierarchical testing first in patients with stage 2 to 3a disease and then for all-comers based on intention-to-treat population.

The ALINA trial showed that disease-free survival (DFS) at 2 years was 93% in the alectinib group and 63% in the chemotherapy group, giving almost 30% absolute difference in disease-free survival. When you look at the intention-to-treat population, which is again treated patients with 1b through 3a disease, the DFS was also numerically, clinically meaningfully better of 93% versus 63% with a hazard ratio of 0.24. It is also important to notice that alectinib in that trial was associated with clinically meaningful benefit with respect to CNS disease-free survival. As you know, patients with ALK mutations have a higher incidence of brain metastasis in general, and therefore medications that have an ability to decrease brain relapse are very important for those patients.

In summary, how do we approach this patient for ALK-fusion lung cancer? 

I have explained that immunotherapy should not be considered. While we know in the ALINA trial that chemotherapy is equal to alectinib, we do not know if chemotherapy followed by alectinib will be better than alectinib alone because that study has not been done. Since chemotherapy has an established efficacy in the adjuvant setting, my approach in those patients have been chemotherapy followed by alectinib, in those patients who are interested in chemotherapy and are able to tolerate chemotherapy. If your patient is not interested in chemotherapy or you do not think that chemotherapy is going to be tolerated by the patient, then alectinib by itself is a reasonable option.