Study Shows Real-World Efficacy of ALK-Inhibition for ALK+ NSCLC

In an interview with Oncology Learning Network, Gwynn Bebb, BMBCh, PhD, University of Calgary, Tom Baker Cancer Centre, and Amanda J.W. Gibson, BSc, Cumming School of Medicine, University of Calgary, Alberta, Canada, discuss the background, findings, and clinical significance of a retrospective real-world study on ALK-inhibiting targeted therapy in patients with ALK-positive non-small cell lung cancer (NSCLC).

What existing data led you and your co-investigators to conduct this research?

A number of clinical trials, including the foundational PROFILE and ALEX clinical trials have shown that drugs which could target ALK-rearrangements are highly effective at controlling this specific type of non-small cell lung cancer (NSCLC). However, we also know that clinical trial populations, by their very nature, are comprised of a highly selected group of lung cancer patients and therefore may not be reflective of the diversity seen in real clinical settings. There is then a great need for oncologists, health researchers and healthcare policy makers to know if the impressive outcomes seen among ALK-rearranged patients treated with ALK-inhibitors in clinical trial settings accurately reflect the outcomes possible within real clinical populations so that standard of care treatment protocols and drug accessibility/funding are in line with what can create the best outcomes for real-world clinical patients.
 
Describe your study and its findings. Were any of the outcomes particularly surprising?

Our study used the philanthropist-supported Glans-Look Lung Cancer Research database, which is a unique population-level dataset situated in a universal healthcare system, which includes detailed demographic, clinical, treatment and outcome data on every patient within the province of Alberta, Canada who has a diagnosis of lung cancer. From here, we could identify every lung cancer patient who had an ALK-rearrangement in their lung cancer cells and who received an ALK-inhibiting drug over a five-year period (2014-2019). We examined what type of ALK-inhibitor they first received and completed a detailed analysis to describe this unique population of patients and accomplish several additional things:

• look closely at the safety and effectiveness of ALK-inhibitors
• examine patient outcomes (survival, side effects)
• investigate how some patient-level factors have the potential to impact response to ALK-inhibitors and ultimately, patient outcome.

We were able to quantify that that the use of ALK-inhibitors in this real-world clinical populations yielded outcomes that actually exceeded that of the foundational ALK-inhibitor clinical trials (PROFILE) and that are in line with contemporary clinical trial cohorts (ALEX), despite the fact that real-world patients are often dissimilar from clinical trial patients in a number of ways. We were also able to identify some features in real-world patients - factors like poor performance status, de novo metastatic disease (as opposed to metastatic disease developing upon relapse) and the presence of brain metastases - that can decrease patient response to ALK-inhibitors and impact patient prognosis.

One of the greatest impacts of this study was that we were able to show, through a case matched analysis, that it is the combination of an ALK-rearrangement and the use of targeted ALK-inhibitors which really makes a huge difference in prognosis in this patient population. Combined with the ability to quantify response and outcome to targeted ALK-inhibitors this study becomes a foundational piece of information to show how important both molecular testing of tumors and access to a series of targeted therapies is for improving the prognosis of patients with lung cancer.

Did your hypothesis align with current results?

Yes, our results showed that that outcomes of our real world, ALK-rearranged NSCLC patients receiving ALK-inhibitors were comparable to those of clinical trial patients. The combination of targeted treatments, as well as the availability of several generations of ALK-inhibitors, appear to be factors which play a significant role in improving the outcomes of ALK-rearranged NSCLC patients, making patients with this oncodriven form of non-small cell lung cancer some of the longest surviving patients with lung cancer.

Do you and your co-investigators intend to expand upon this research?

Absolutely! Treatments for ALK-rearranged NSCLC are constantly evolving so we will continue to follow and expand this cohort to investigate the contribution of newer generation ALK-inhibiting drugs in the overall improvement of outcomes in this particular population. Additionally, ALK-rearranged NSCLC represents just one of several genetically distinct, oncodriven types of NSCLC for which targeted therapies are now available, and so our work also continues in investigating the effectiveness, safety and tolerability of targeted therapies in patients with other types of NSCLC, including a current project of similar scope investigating the use of targeted therapies in ROS1-rearranged NSCLC.

Is there anything else pertaining to your/this research and findings that you would like to add?

I think it is important to note how significant this type of study is in quantifying how new therapies perform among the highly diverse patients encountered in real clinical practice. It is reassuring that the monies spent by the provider have the impact promised by the data that led to the approval. Reliable sources of comprehensive, population-level, real-world data in a setting which minimizes potential disparities in healthcare access/funding, like the Glans-Look Lung Cancer Research database, are exceedingly rare and this limits access to high quality data that be used in this sort of in-depth retrospective review. We believe that this type of data and this kind of study are key to quantifying the role of targeted drugs in oncodriven tumors, and ensuring their funding, accessibility and ongoing developing along with reinforcing that molecular testing of tumors is essential best practice in the management of lung cancer.