Understanding Efficacy, Clinical Use of Lung Cancer Treatment With Phase 3 Data

Martin Edelman, MD, chair, Department of Hematology/Oncology, deputy director of clinical research, Fox Chase Cancer Center, discusses the disease burden of non-small cell lung cancer, as well as the findings from a phase 3 trial that supported approval of an adjuvant treatment by the US Food and Drug Administration this year.

Read the full transcript:

Welcome back to PopHealth Perspectives, a conversation with the Population Health Learning Network where we combine expert commentary and exclusive insight into key issues in population health management and more.

Today we are joined by Dr Martin Edelman, deputy director of clinical research at Fox Chase Cancer Center. He discusses the disease burden of non-small cell lung cancer, as well as the findings from a phase 3 trial that supported approval of an adjuvant treatment by the FDA this year. Dr Edelman?

My name is Martin Edelman. I am a physician, a medical oncologist focusing on thoracic oncology, which I've done for about 30 years now. I am a professor and chair of the Department of Hematology/Oncology and deputy director for clinical research at the Fox Chase Cancer Center in Philadelphia, Pennsylvania.

Before we jump into the actual research, could you briefly tell us about the disease burden and unmet need in non-small cell lung cancer?

Lung cancer's a very common entity in the United States. There are approximately 225,000 new cases of lung cancer, of which 90%, or approximately 200,000, are non-small cell lung cancer.

Of those, one could estimate approximately 100,000 or so will fall, 50% in total, into stages 1 through 3, and therefore, potentially the subject of the paper that we'll discuss today.

Of the relative rates of the different types of cancers, lung cancer is the second most common cancer in both men and women in terms of incidence, and overwhelmingly the most common cause of cancer death, exceeding the next three malignancies in men and the next two in women.

Pivoting more into the research, what would you say are the key takeaways from the IMPower010 study?

The IMPower010 study is a landmark trial that now has validated and resulted in the FDA approval of atezolizumab, an immunotherapy drug for the adjuvant treatment of resected stages 2 to 3A lung cancer. Those are patients who had disease that was confined to a lobe of the lung with lymph node involvement, either localized or within the regional mediastinal area.

Can you talk a little bit about the findings from that study?

The study was initially presented at the ASCO 2021 meeting by Dr Wakelee from Stanford, and then with subsequent analyses presented at the World Conference on Lung Cancer, and European Society for Medical Oncology, and fully published in The Lancet in the October 9, 2021 issue, and as I mentioned earlier, resulting in FDA approval in mid-October.

This was an international, randomized trial where approximately 1000 patients were randomized to either atezolizumab or best supportive care after they had surgery and then adjuvant chemotherapy.

The results, the primary endpoint of the study was disease-free survival in patients who were 2 to 3A with at least one percent of PD-L1, an important marker for responsiveness to immunotherapy.

In that situation, there was a statistically and clinically significant improvement of disease-free survival with a hazard ratio of .66, indicating approximately 33%-34% reduction in risk of disease progression. This was, again, felt to be significant enough to result in FDA approval.

There were other patients who enrolled in the study and a variety of subset analyses that were performed. One of the key issues in this, which has yet to be fully mature, is the final overall survival, which essentially means cure and how much this will actually improve the rate of cure in non-small cell lung cancer.

Given results from other trials of anti-PD-1 and PD-L1 drugs in locally advanced and advanced disease, I have little doubt that overall survival will be significantly impacted.

The questions that remain with this are exactly which of these patients will benefit. Can we best predict who will benefit from the use of these drugs? There were a number of subset analyses presented and with some confounding factors.

Probably the most interesting and potentially clinically important one is that the patients with PD-L1 that exceeded 50% drove the results for the entire population. That is to say, that's where almost all of the benefit was seen, with far less benefit seen in the 1%-49% group.

It may be that ultimately the patients who should receive these therapies will be those with resected stages 2 to 3A disease who have elevated PD-L1. However, I would note that the FDA approval is for all patients who are greater than PD-L1 1%.

How might these findings impact current and future practice?

The current practice is now very clear with this full approval based upon a randomized phase 3 trial. Essentially any patient who has had a resected non-small cell lung cancer meeting the staging criteria of the study should be offered treatment with atezolizumab for one year.

Future questions that are now the subject of ongoing trials are, should immunotherapy be given concurrent with chemotherapy? It is quite possible that if it's done that way, the results may eliminate the advantage seen for PD-L1 elevated patients.

Also, whether or not it should be combined with other immunotherapy agents, which again could obviate the need for PD-L1 or at least the predictive or prognostic value of PD-L1, but all of that remains in the future. Many of those studies are either ongoing, and some have even been completed, but the results are still pending.

What should payers keep top-of-mind regarding coverage for non-small lung cancer treatments?

From the standpoint of a payer, right now, this is a clear and unequivocal indication for the use of immunotherapy. Unquestionably, this has the potential to increase costs, but it will also clearly increase survival, so it should not be subject to review or disagreement.

From the standpoint of a payer or, for that matter, a physician, good medical care would indicate that the results of this trial demonstrate that this is not something that is yet ready to be extended to those who have lower stage of disease, so specifically patients with 1B disease, which were included in the trial. But that cohort did not achieve significance and was not part of the FDA approval, so they would not be a group that would be eligible for this treatment.

Is there anything else you'd like to add today?

Other than, as I said before, this is something which is merely the first of what will be many studies that will be released, and this will be a rapidly-developing area. We've seen this with these improvements in the treatment of lung cancer with immunotherapy. That came quite rapidly a few years ago.

I suspect that over the next three years the questions that I pose, such as the value of combining this with chemotherapy, with other immunotherapy agents such as anti-CTLA-4 drugs like ipilimumab, will be addressed and hopefully answered in a positive manner. Thank you.

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