Understanding and Managing Disease Heterogeneity in Small Cell Lung Cancer

In a conversation with CancerNetwork^®, Anne Chiang, MD, PhD, discussed noteworthy research initiatives that have the potential to improve outcomes among patients with small cell lung cancer (SCLC). She specifically highlighted the methodology of the ongoing phase 2 SWOG S2409 PRISM trial (NCT06769126), which she serves as chair.

According to Chiang, an associate professor of Medicine in the Section of Medical Oncology at Yale School of Medicine, the trial will include 800 patients with SCLC who will provide tumor tissue during the time of induction chemoimmunotherapy. Based on subsequent immunohistochemistry (IHC) results, patients will receive one of multiple immunotherapy-based regimens that encompass the use of different modalities like PARP inhibitors and natural killer (NK) cell activators. This prospective trial, she described, may help in understanding disease heterogeneity in SCLC and tailoring specific treatment strategies to different patient subgroups.

Transcript:

The biology of [SCLC is something] we’re learning more about. One of the aspects is, just like the strategy in non–small cell [lung cancer], where we started to understand the heterogeneity, can we start to dial in our therapies for different subtypes? I’ll talk about a trial that is [from] a cooperative group: the SWOG S2409 PRISM trial that I happen to be the chair of. There’s a whole slew of people who have been involved, including my co-chair Alberto Chiappori, MD, [from Moffitt Cancer Center], and Carl M. Gay, MD, PhD, and Lauren Averett Byers, MD, at MD Anderson [Cancer Center].

In the PRISM trial, we’re going to have over 800 patients where we ask for tissue during their frontline induction therapy with [chemoimmunotherapy]. Then, based on their subtype, are they A, N, P, or I? What is their SLFN11 status by IHC? Then, those patients will be randomly [assigned] to the biomarker-directed therapy plus [immunotherapy] vs [immunotherapy alone arm]. If you have a neuroendocrine subtype—A or N—and you are SLFN11 positive, you’ll get a PARP inhibitor plus [immunotherapy] vs [immunotherapy alone]. If you have subtype I, you’re going to get monalizumab, which is an NK cell activator, plus the [immunotherapy] vs [immunotherapy] alone, and so forth. We’re excited about that trial. It’s a prospective trial, and most of all, we’re going to be getting tissue from a slew of patients so that we can really move the field forward. [I am] very excited about that.