Defining Maintenance Therapy and Unmet Needs in ES-SCLC

Extensive-stage small cell lung cancer (ES-SCLC) remains one of oncology’s most formidable challenges: a disease defined by its aggressive biology, near-universal recurrence, and a treatment landscape that is only beginning to diversify. During a live Community Case Forum in Bridgewater, New Jersey, Joshua Sabari, MD, thoracic oncologist at NYU Langone Health, discusses these clinical complexities.

What does “maintenance therapy” mean in a disease where almost every patient will relapse? Who is the right candidate for lurbinectedin (Zepzelca) after first-line chemotherapy, and how should oncologists weigh tolerability against a patient’s drive to stay as aggressive as possible? Sabari addresses these questions while also touching on the evolving and increasingly limited role of prophylactic cranial irradiation (PCI), the practical value of supportive agents like trilaciclib (Cosela), and what he sees as the field’s most pressing unmet need: a biomarker to guide treatment selection in a space where regimens are still largely biomarker-agnostic.

This is part 2 of a 2-part series. Read part 1 here.

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Targeted Oncology: What are the challenges of defining maintenance therapy?

Joshua Sabari, MD: Maybe a patient who got 2 cycles of carboplatin-etoposide and has growth of their disease vs a patient who had 4 cycles and had 60% regression on the first scan and then another 20% regression in their tumor. How would you think about maintenance in those 2 patients? What is maintenance?Is it second line or is it first line? Maintenance is a real thing to talk about, biologically, in this population. We know [most] of these patients are going to recur… So, is first-line maintenance [considered] early second line or not? It’s a real thought-provoking question.

Who would you consider as a candidate for maintenance with lurbinectedin?

I think for a very fit patient, a patient who’s active, who wants to be as aggressive as possible, I would consider lurbinectedin maintenance. I don’t use lurbinectedin maintenance in all of my patients, but I at least talk about it, and I offer it to many of my patients.

My experience with patients is, if a patient’s goal is to be alive, they’re willing to take on a bit more toxicity, and it’s our job as oncologists to manage that toxicity. So, if I have a patient on lurbinectedin maintenance and their [blood cell] counts are low or they’re not feeling well, I hold [or] I dose reduce, and I think that’s what we’re supposed to do when we’re treating patients.

What is your experience with trilaciclib or other supportive medications in ES-SCLC?

Trilaciclib is a CDK4/6 inhibitor. It’s a short-acting inhibitor, and it actually preserves the marrow. I haven’t used it myself. I’ve used [granulocyte colony-stimulating factor (G-CSF)], and I do find that supportive medications are helpful in this patient population, especially when their marrow is somewhat compromised. When you’re making the decision with the patient, you have to make sure their marrow is going to be able to tolerate this therapy. I’m thinking about using them more to preserve their counts. I think having some strategy to prevent marrow failure, neutropenia, or anemia is going to be important when thinking about maintenance strategies with lurbinectedin.

How are the treatment paradigms evolving in ES-SCLC?

I think in the current literature for extensive-stage disease, the role for PCI has become more limited. There’s a Japanese study, and it was a futile study, looking at PCI vs no PCI.¹ It’s really fallen out of favor, especially in the immunotherapy era.

We got a lot of referrals from community sites to do the first 1 or 2 cycles and then send the patient back to the community. I’d say over the last 3 to 6 months, it’s dropped off a lot, meaning I think a lot of [physicians] in the community are willing to do it. I’ve even seen people give it in the outpatient setting.

What is an unmet need you see in ES-SCLC?

We are using agnostic regimens in all patients. The idea of having a biomarker to select [in which patients] tarlatamab [Imdelltra] or lurbinectedin could work better in would help us differentiate. I think a lot of these [antibody-drug conjugates (ADCs)] coming have similar payloads. How we differentiate those is going to be really important.

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DISCLOSURES: Sabari previously reported consulting or Advisory role with AstraZeneca, Pfizer, Regeneron, Medscape, Takeda, Janssen, Genentech/Roche, Mirati Therapeutics, AbbVie, Loxo/Lilly, and Sanofi, and institutional support from Janssen, Loxo/Lilly, Mirati Therapeutics, and Regeneron.

REFERENCE

1. Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017 May;18(5):663-671. doi:10.1016/S1470-2045(17)30230-9. Epub 2017 Mar 23. PMID: 28343976.