David Chun Cheong Tsui, MD, Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, discusses results from a study examining the real-world adoption and early clinical outcomes of atezolizumab plus carboplatin and etoposide among patients with extensive-stage small cell lung cancer (SCLC).

This study was presented at ESMO Congress 2021. 

Transcript

Hi, my name is David Tsui. I'm a Senior Thoracic Oncology Fellow at the Anschutz Cancer Center in Colorado. I'm delighted to discuss our study in collaboration with Genentech and Flatiron entitled "Adoption and Early Clinical Outcomes of Atezolizumab Plus Carboplatin and Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer in the Real-World Setting" presented at ESMO 2021.

As we all know, small cell lung cancer is challenging disease to treat and carries a poor prognosis. There had been a lack of progress of treatment until the IMpower133 study, which established combination of chemotherapy and immunotherapy as a first-line treatment for extensive-stage small cell lung cancer.

That study was presented and published in September 2018 and show that the addition of atezolizumab, an anti-PD-L1 antibody, to carboplatin and etoposide resulted in a 1-month median PFS benefit with a hazard ratio of 0.77, and a 2-month median OS benefit with a hazard ratio of 0.7 over chemotherapy alone in extensive stage small cell lung cancer.

In that study, 55% of patients who were less 65 years old, ECOG status must be 0 to 1 in order to eligible for enrollment. While patients with asymptomatic brain mets were allowed, they only comprised about 9% of the trial population. While the data is encouraging, it does not completely reflect the real-world patient population.

In addition, prophylactic cranial irradiation was permitted, but thoracic radiotherapy was not allowed. Depending on the institution one practices at, both of these are adopted approaches in the pre-immunotherapy era.

In collaboration with Genentech and Flatiron we set out to ask: Now that atezolizumab plus carboplatin and etoposide is a widely-adopted regimen, how does the outcome compare in the real world to the trial? Also, what are the practice patterns in terms of prophylactic cranial irradiation and thoracic radiotherapy in the real world in the immunotherapy era?

Using the Flatiron database, we identified 493 patients with extensive stage small lung cancer who were treated with first-line atezolizumab plus carboplatin and etoposide between September 25, 2018, when the IMpower133 trial results were initially published, and April 30, 2020, which I will call the real-world cohort from now on.

There are several key differences in patient demographics between the real-world population and the IMpower133 trial population. About two-thirds of the patients were at least 65 years old in the real-world cohort, compared to only 45% in the IMpower133 trial.

In the real-world cohort, 21% of patients were ECOG 2 to 3, while all patients had ECOG 0 to 1 in the IMpower133 trial. Finally, about 20% of real-world cohort patients had brain mets at baseline, compared to 9% of the patients in the IMpower133 trial who had treated asymptomatic brain mets.

We also identified a subset of patients in our real-world cohort that fits the IMpower133 trial inclusion/exclusion criteria, and we call it the real-world IMpower133 trial eligible like cohort.

Now, despite all these differences in patient characteristics, with a median follow-up of about seven months in our study, the real-world cohort has a median PFS of 5.2 months and a median treatment duration of 5.7 months, which are very similar to the IMpower133 trial outcomes.

In the real-world IMpower133 trial eligible light cohort, the outcomes were numerically even better, with a median PFS of 5.8 months, and a median treatment duration of 6.2 months. Our data suggests that, even with the poorer patient prognostic factors in the real-world cohort, the outcomes are very similar to what was described in the trial.

In terms of practice patterns, we found that about half of patients with baseline brain mets received local therapy with either surgery or radiation.

For the patient population that has reached the maintenance atezolizumab phase of treatment, about 30% received thoracic radiotherapy, regardless of intent, and about 13% received brain radiotherapy in the absence of any prior documented brain mets.

Because of the lack of radiation dose and fractionation data, we were unable to determine the intent of these therapy. However, we think this can give us a hint of the practice patterns, and thus, allow to put into context of the ongoing trials examining the role of radiotherapy in the immunotherapy era for treatment of extensive-stage small cell lung cancer.

In summary, our study further reinforced the efficacy of atezolizumab plus carboplatin and etoposide as a first-line regimen in extensive-stage small cell lung cancer in a real-world cohort, with a poorer prognostic factors compared to the trial, and show, although with limitations, that thoracic radiotherapy and prophylactic cranial irradiation is likely adopted in a small subset of patients in the real-world in the immunotherapy era.

Thank you for listening.

Tsui DCC, Polito L, Madhavan S, et al. Adoption and early clinical outcomes of atezolizumab (atezo) + carboplatin and etoposide (CE) in patients with extensive-stage small cell lung cancer (ES-SCLC) in the real-world (RW) setting. Presented at: the ESMO Congress 2021; September 17-21, 2021; virtual. Abstract 1650P.