Therapy for Stage IV Non–Small-Cell Lung Cancer Without Driver Alterations Guideline

An interview with Dr. Nasser Hanna from Indiana University Simon Cancer Center and Dr. Gregory Masters from Helen F. Graham Cancer Center and Research Institute on "Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Joint Guideline Update." This guideline provides recommendations on systemic therapy treatment options for patients with stage IV non-small-cell lung cancer (NSCLC) without driver alterations in epidermal growth factor receptor or ALK, based on histology, PD-L1 status, and/or the presence or absence of contraindications. Read the full guideline at www.asco.org/thoracic-cancer-guidelines.

Transcript

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Hello, and welcome to the ASCO Guidelines Podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at podcasts.asco.org.

My name is Brittany Harvey. And today, I'm interviewing Dr. Nasser Hanna from Indiana University's Simon Cancer Center and Dr. Gregory Masters from Helen F. Graham Cancer Center and Research Institute, co-chairs on therapy for stage IV, non-small cell lung cancer without driver alterations, ASCO and CCO Joint Guideline Update. Thank you for being here today Dr. Hanna and Dr. Masters.

Thank you. Glad to be with you.

My pleasure. Thanks.

First, Dr. Hanna, can you give us a general overview of what this guideline covers?

Sure. So the ASCO guidelines for the treatment of patients with stage IV, non-small cell lung cancer were last updated in 2017. And since that time, there has been a tremendous amount of change that has taken place. The 2017 guidelines included recommendations for basically three subgroups-- those patients with non-small cell lung cancer who have certain targetable DNA mutations and those who do not have those mutations but have a PD-L1 score of 50% or higher and then everyone else.

But because of the rapid and vast changes that have taken place, we decided to make a separate guideline for those with targetable DNA mutations and to focus this current guideline on those without the targetable mutations. So within that context, this guideline categorizes patients by whether their tumors have a PD-L1 score of 0% to 49% or those who have a PD-L1 score or 50% or greater.

And within those categories, recommendations are characterized based upon whether the patient has squamous cell histology or non-squamous cell histology. And we also consider whether patients are candidates for chemotherapy or perhaps even those that decline chemotherapy and whether they have any contraindications for immunotherapy.

So what distinguishes these guidelines from other guidelines is our attempt to adhere to the strongest available evidence-based medicine. And while not every iteration of clinical management can be covered, these guidelines provide oncologists with a strong, evidence-based roadmap to treat the vast majority of patients with non-small cell lung cancer.

So as a result of this collective effort by ASCO staff and the guideline writing committee, this report offers a substantial amount of change to the recommendations from the clinical practices guidelines provided in 2017. In 2017, the only recommendations for the use of immunotherapy were in the first line setting for patients who had a PD-L1 score of greater than 50% and in the second line setting of patients progressing after first line chemo.

But these updated guidelines include the incorporation of immunotherapy in all subgroups of patients regardless of histology and PD-L1 score. So as a result, there are about three times the number of options to consider in the first line setting with these new guidelines compared to the 2017 guidelines. However, the 2020 guidelines provides a preferred treatment regimen for each situation to simplify the decision making process for most patients.

And what are those key recommendations of this guideline update for patients without driver alterations?

So the key changes for 2020 is the incorporation of immunotherapy into nearly all settings in the first line setting, regardless of tumor histology and regardless of PD-L1 score. For those patients who have a PD-L1 score of 50% or higher, single agent pembrolizumab remains the preferred treatment for most patients.

But new evidence does provide a rationale for giving select patients chemotherapy, either carbo and pemetrexed if they have non-squamous, or carbo plus paclitaxel or nab-paclitaxel for squamous plus the addition of pembrolizumab in this subgroup of patients. For those patients with PD-L1 scores of 0% to 49% who are eligible and willing to take chemotherapy, these new guidelines recommend chemotherapy plus pembrolizumab.

For those who have a PD-L1 score of 1% to 49% are not appropriate for chemo or decline chemotherapy, these guidelines suggest single agent pembrolizumab as a reasonable option. The guidelines also provide the option of alternative chemo immunotherapy regimens to be used in patients with non-squamous, non small-cell that were not included in the prior guidelines.

And while these are not necessarily preferred for most patients, select patients can be considered for these regimens, which include the immunotherapy drug, atezolizumab, and combination chemo with atezolizumab and bevacizumab. And the guidelines provide some commentary on potential scenarios in which these options should be considered.

Dr. Masters, why is this guideline important, and how will it change practice?

Well, the new ASCO CCO joint non-small cell lung cancer guideline update is important in that it clarifies recommendations for an international audience and is co-sponsored by the American Society for Clinical Oncology and Cancer Care Ontario. These guidelines were developed through a rigorous, evidence-based process with a broad range of experts, including a multidisciplinary team of clinicians, researchers, data specialists, and patient representatives.

The new guideline update provides a comprehensive review and analysis of the current literature on the treatment of advanced non-small cell lung cancer. The current update also includes a data supplement with evidence tables, slide sets, and links to patient information through cancer.net, ASCO's patient information website.

In an increasingly complicated environment for oncologists, managing patients with advanced cancer, we're learning how to incorporate molecular testing and other biomarkers. And this guideline will help change day-to-day practice for clinicians as they implement these recommendations. This guideline will help clarify the optimal treatment strategies for non-small cell lung cancer patients without driver gene mutations and allow individualization based on tumor histology and immunotherapy biomarkers, such as PD-L1 testing.

At the same time, the update allows clinicians to use their individual judgment and experience to incorporate unique, intangible characteristics of patients. It also emphasizes the importance of patient preferences in deciding the optimal care for an individual affected by advanced non-small cell lung cancer.

And finally, how will these guideline recommendations impact patients?

The broad range of experts who've contributed to these guidelines includes a multidisciplinary team, including clinicians, researchers, data specialists, and patient representatives. This assures patients of a consensus opinion based on the available clinical research on treating advanced non-small cell lung cancer. It provides clinicians with the best up-to-date distillation of the many complicated trials of chemotherapy and immune checkpoint inhibitor therapy in an area where patient-centered, precision medicine dictates the optimal treatment strategies.

We incorporate molecular testing in these guidelines, although this particular guideline is directed at patients without driver gene mutations. We include recommendations on implementation of chemotherapy and immunotherapy based on the best available data on biomarker testing for PD-L1.

We recognize, however, that new research continues into treatment strategies and molecular analysis to help guide incorporation of targeted therapy and immunotherapy. We recognize that new treatment options and combinations will become available, and new testing techniques will help guide the decision process in the future. We plan to continue to analyze the available research and update these guidelines as clinically indicated to provide the best options for our patients.

Most of our patients will still be treated with palliative intent. But a growing number of patients have sustained control of their cancer with recent studies and updates suggesting that up to 25% of patients may have control of their disease for five years or longer. Now that more patients can maintain their quality of life with prolonged survival, with the current therapy, it is also critical that we continue to look to patient reported outcomes as an important way of defining the best options for our patients.

Thank you both for your work on this ASCO CCO guideline update for therapy for stage IV, non-small cell lung cancer without driver alterations and for coming on the podcast today to provide an interview, Dr. Hanna and Dr. Masters.

Thanks for having us on the program. And we have enjoyed being part of the process.

Thank you.

And thank you to all our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available and iTunes or the Google Play Store. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

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