Navigating the Complexities of SCLC Treatment Through the Lines of Therapy

Small cell lung cancer (SCLC) remains one of oncology's most formidable challenges: a disease defined by its aggressive biology, initial chemosensitivity, and ultimately poor long-term outcomes. Despite advances in immunotherapy and evolving treatment guidelines, many patients never make it to later lines of therapy, underscoring the urgent need for optimized sequencing and patient selection.

During a live Community Case Forum in Bridgewater, MD, Joshua Sabari, MD, thoracic oncologist at NYU Langone Health, walked through the real-world treatment landscape, from frontline chemoimmunotherapy decisions to the nuances of chemotherapy duration and emerging guideline updates.

Targeted Oncology: What challenges does SCLC present?

Joshua Sabari, MD: We know that SCLC is a recalcitrant disease. We talk a lot about the biology: p53 and RB1 [mutations], tumor suppressor gene loss. SCLC is very responsive to chemotherapy, but patients generally do not do well.

What does attrition look like through lines of therapy?

We know there's a very high rate of attrition. We know that chemotherapy and immunotherapy is a standard of care, but in a [Flatiron Health] database of 2225 patients, 18% of patients did not get immunotherapy in the frontline setting.¹ What’s quite interesting is that, if you look at later lines, there’s a significant drop off in the maintenance settings and second line. Only 40% of patients in this cohort received second-line therapy, and only 13% received third-line therapy.

Are there cases where you would not use immunotherapy in the frontline setting?

[I would not use immunotherapy in patients with] autoimmune disease or cardiac transplant patients. I’ve seen a kidney transplant patient with SCLC, and you might not want to give them immunotherapy.

CASE SUMMARY

• A 73-year-old woman presents with dyspnea on mild exertion, productive cough, chest pain, fatigue, anorexia, and a recent, unintentional 18-lb weight loss.
• Past medical history
  • Hypertension, well controlled on candesartan/hydrochlorothiazide daily
  • 45 pack year smoking history and current smoker
• Staging: T3N3M1b — IV
  • Extensive-stage SCLC

Where do you see the use of cisplatin in patients like this?

I don’t commonly use cisplatin. In the frontline setting in Europe, it is still a commonly used regimen in some areas.

Could you discuss the updated NCCN guidelines in SCLC?

New in the NCCN guidelines is lurbinectedin [Zepzelca] and atezolizumab [Tecentriq] maintenance.² There are other recommended regimens but using chemotherapy and immunotherapy in the frontline setting are critical.

What are your thoughts on giving more than 4 cycles of chemotherapy in this setting?

Most people are using 4 cycles. We did 4 to 6 cycles in Europe. There, we used to do 6 a lot more, because we thought that maybe if you consolidate further, patients did better.³ But there was a study of 4 vs 6 cycles of carboplatin-etoposide, and there was no difference between 4 and 6 cycles. And with 6 cycles, you saw much higher rates of neutropenia and anemia, and it actually decreased the chances of patients getting subsequent therapy, so it did not improve survival.

But I think as we now have better therapeutics, both on the chemotherapy and immunotherapy ends, is the extra 2 cycles helpful or not in some patients when they’re deriving benefit?

REFERENCES

1. Iams W, Miller T, Reiss S, et al. Patient characteristics and treatment patterns in extensive-stage small cell lung cancer (ES-SCLC). Presented at ISPOR Annual. 2025.

2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Small Cell Lung Cancer. Version 2.2026. NCCN; 2025. Accessed April 23, 2026. https://www.nccn.org

3. Veslemes M, Polyzos A, Latsi P, et al. Optimal duration of chemotherapy in small cell lung cancer: a randomized study of 4 versus 6 cycles of cisplatin-etoposide. J Chemother. 1998 Apr;10(2):136-40. doi: 10.1179/joc.1998.10.2.136. PMID: 9603640.