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The ADRIATIC Trial in Limited-Stage SCLC

Insights From: Jacob Sands, MD, Dana-Farber Cancer Institute
Published: Tuesday, Dec 03, 2019



Transcript: 

Jacob Sands, MD: Now we have the ADRIATIC study, which is in limited-stage small cell lung cancer. In this study, we see patients being treated with standard-of-care chemotherapy and radiation and then randomized to get durvalumab maintenance versus observation. This will provide us an opportunity to see if adding in the immunotherapy in this setting really adds the benefit that we’ve seen from studies like CASPIAN in the extensive-stage setting, and PACIFIC in the non–small cell lung cancer setting.

Even in the limited-stage setting of small cell lung cancer, this is a diagnosis that tends to metastasize quickly and spread aggressively. And so even in that setting, when it appears like limited-stage disease, there are a number of patients treated with chemotherapy and radiation who don’t end up being cured. In small cell lung cancer, there is especially logic to adding in more aggressive therapy, particularly when it can be tolerated. Now, we’ve seen from the PACIFIC data in non–small cell lung cancer this paradigm of adding in immunotherapy, adding in durvalumab, after initial chemotherapy and radiation. And more recently, we’ve seen data presented on a poster at ASCO [the American Society of Clinical Oncology Annual Meeting] with atezolizumab with chemotherapy and radiation. Both of these settings show no substantial increase in pneumonitis. I think at the start of the PACIFIC study, there was reasonable concern that we might see this, given that radiation can cause pneumonitis and so can the checkpoint inhibitors. And fortunately, this is not something we’ve really seen, and this has generally been very well tolerated.

This provides a strong rationale to add durvalumab into the limited-stage small cell lung cancer setting after chemotherapy and radiation, having seen this drug tolerated well after chemotherapy and radiation in the non–small cell lung cancer setting, as well as showing good efficacy from the CASPIAN study in extensive-stage small cell lung cancer.

The limited-stage small cell lung cancer setting is not necessarily equivalent to what we see in non–small cell lung cancer. This does tend to be more aggressive disease, although the radiation fields really can end up being broad in both of those. That’s not necessarily a significant difference that we see. The biggest difference between small cell and non–small cell lung cancer is just the urgency of getting started with treatment in small cell lung cancer. Oftentimes, we’ll get a dose of chemotherapy in as quickly as possible, and then do the radiation planning to add in radiation with later cycles, ideally with cycle 2. Sometimes it can even be a little later than that.

We’re in an academically exciting time in small cell lung cancer. We’ve laid out the fact that outcomes have been very poor historically, and the significant advance that these checkpoint inhibitors have really brought forward. There are also a lot of novel therapies that are currently in development. We see some things a little further along, like lurbinectedin, which has shown some improvement in the toxicity profile, maybe more than anything. And then we have more novel treatments now with EZH2 inhibitors, bispecific T-cell engagers, TIM3 inhibitors, and Aurora kinase inhibitors. These are various classes, and these are clinical trials that we have available here at Dana-Farber Cancer Institute [in Boston, Massachusetts]. We’re enrolling patients on these studies and have seen some responses in settings where, previously, there really weren’t good options. What will pan out from these is still further in development. There are also other more novel therapies even further beyond that are now in the pipeline to get to clinic. So we are really seeing some significant advances in this very difficult-to-treat population of patients.

Transcript Edited for Clarity

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Transcript: 

Jacob Sands, MD: Now we have the ADRIATIC study, which is in limited-stage small cell lung cancer. In this study, we see patients being treated with standard-of-care chemotherapy and radiation and then randomized to get durvalumab maintenance versus observation. This will provide us an opportunity to see if adding in the immunotherapy in this setting really adds the benefit that we’ve seen from studies like CASPIAN in the extensive-stage setting, and PACIFIC in the non–small cell lung cancer setting.

Even in the limited-stage setting of small cell lung cancer, this is a diagnosis that tends to metastasize quickly and spread aggressively. And so even in that setting, when it appears like limited-stage disease, there are a number of patients treated with chemotherapy and radiation who don’t end up being cured. In small cell lung cancer, there is especially logic to adding in more aggressive therapy, particularly when it can be tolerated. Now, we’ve seen from the PACIFIC data in non–small cell lung cancer this paradigm of adding in immunotherapy, adding in durvalumab, after initial chemotherapy and radiation. And more recently, we’ve seen data presented on a poster at ASCO [the American Society of Clinical Oncology Annual Meeting] with atezolizumab with chemotherapy and radiation. Both of these settings show no substantial increase in pneumonitis. I think at the start of the PACIFIC study, there was reasonable concern that we might see this, given that radiation can cause pneumonitis and so can the checkpoint inhibitors. And fortunately, this is not something we’ve really seen, and this has generally been very well tolerated.

This provides a strong rationale to add durvalumab into the limited-stage small cell lung cancer setting after chemotherapy and radiation, having seen this drug tolerated well after chemotherapy and radiation in the non–small cell lung cancer setting, as well as showing good efficacy from the CASPIAN study in extensive-stage small cell lung cancer.

The limited-stage small cell lung cancer setting is not necessarily equivalent to what we see in non–small cell lung cancer. This does tend to be more aggressive disease, although the radiation fields really can end up being broad in both of those. That’s not necessarily a significant difference that we see. The biggest difference between small cell and non–small cell lung cancer is just the urgency of getting started with treatment in small cell lung cancer. Oftentimes, we’ll get a dose of chemotherapy in as quickly as possible, and then do the radiation planning to add in radiation with later cycles, ideally with cycle 2. Sometimes it can even be a little later than that.

We’re in an academically exciting time in small cell lung cancer. We’ve laid out the fact that outcomes have been very poor historically, and the significant advance that these checkpoint inhibitors have really brought forward. There are also a lot of novel therapies that are currently in development. We see some things a little further along, like lurbinectedin, which has shown some improvement in the toxicity profile, maybe more than anything. And then we have more novel treatments now with EZH2 inhibitors, bispecific T-cell engagers, TIM3 inhibitors, and Aurora kinase inhibitors. These are various classes, and these are clinical trials that we have available here at Dana-Farber Cancer Institute [in Boston, Massachusetts]. We’re enrolling patients on these studies and have seen some responses in settings where, previously, there really weren’t good options. What will pan out from these is still further in development. There are also other more novel therapies even further beyond that are now in the pipeline to get to clinic. So we are really seeing some significant advances in this very difficult-to-treat population of patients.

Transcript Edited for Clarity
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