1L Treatment: Induction and Maintenance

Platinum-based chemotherapy has been the longtime standard of care for 1L induction treatment.1 Treatment recommendations may also include radiotherapy depending on staging. Despite high response rates to platinum-based induction, nearly all patients will relapse.

The recent addition of IOs to 1L ES-SCLC treatment has improved patient outcomes—robust clinical and real-world evidence shows that ES-SCLC patients who received maintenance therapy achieved longer survival outcomes than those who did not.2,3

In an exploratory analysis of a landmark phase 3 trial2,a:

The addition of maintenance immunotherapy improved median OS by

41%

(HR: 0.59; 95% CI: 0.43-0.80)

Among patients who received maintenance therapy, median OS was

12.5 months

vs 8.4 months in those who did not

aAn exploratory analysis of only those patients who responded to induction treatment in the IMpower133 trial and who received at least one dose of maintenance atezolizumab (n=154) or placebo (n=164). A multivariate Cox model was used to evaluate the treatment effect on OS, measured from the start of maintenance treatment. Covariates were ECOG PS, sex, age, brain or liver metastases, lactate dehydrogenase level, sum of longest diameters, and number of metastatic sites.

Limitations: This is a post-randomization exploratory analysis that did not include a control arm with only patients who received induction but not maintenance therapy. Results are not powered for statistical significance. These data should be interpreted with caution.

 

2025 NCCN CLINICAL PRACTICE GUIDELINES IN ONCOLOGY (NCCN GUIDELINES®) RECOMMEND4:

  • Following induction, maintenance immunotherapy is a preferred regimen for ES-SCLC
  • Maintenance immunotherapy should continue until progression or intolerable toxicity

Only ~40% of SCLC patients who receive 1L treatment will go on to receive 2L treatment, and less than 40% of those patients will receive 3L treatment.5

Using your best options as early as possible may give patients the opportunity for the best possible outcomes

LIMITED STAGE: CHEMOTHERAPY AND RADIOTHERAPY

  • The role of concomitant chemotherapy with radiotherapy is well established in the management of LS disease1

Initial Treatment Options for LS-SCLC1,6

Small Cell Lung Cancer (SCLC) Chemotherapy Drawing

COMBINATION CHEMOTHERAPY

Use in
LS-SCLC

Recommended first-line therapy is platinum plus etoposide (platinum doublet) for eligible patients4,a
  • For patients who respond with at least disease control:
    • Continue with immunotherapy alone until:
      • Disease progression
      • Unacceptable toxicity
      • A maximum of 24 months

Efficacy and Safety Results

Superior to alternatives in efficacy and toxicity
Small Cell Lung Cancer (SCLC) Radiotherapy Drawing

RADIOTHERAPY

Use in
LS-SCLC

Given concurrently or sequentially to combination chemotherapy4,a

Efficacy and Safety Results

Chemoradiotherapy results in:
  • Response rates of 70-90%
  • Median overall survival of 24-30 months
  • 5-year overall survival rates of 25-30%
However, chemoradiotherapy increases the risk of:
  • Esophagitis
  • Pulmonary toxicity
  • Hematologic toxicity
Brain Drawing

PROPHYLACTIC CRANIAL IRRADIATION (PCI)b

Use in
LS-SCLC

Offered to patients who respond to initial concurrent chemoradiotherapy (CRT) and have a performance status of 0-11

Evidence supporting PCI is not as clear in patients1:
  • With a performance status of 2 after CRT
  • >70 years of age
  • With pre-existing neurological conditions

Efficacy and Safety Results

Meta-analysis of data from PCI trials shows:
  • Nearly 50% reduction in the 3-year incidence of brain metastases
  • Prevention, not merely a delay, of the emergence of brain metastases

aSee the NCCN Guidelines® for SCLC for detailed recommendations.

bCurrent randomized trials are evaluating whether brain MRI surveillance alone is non-inferior to MRI surveillance plus PCI on overall survival.4

In LS-SCLC, patients do not receive maintenance therapy as part of their initial regimen.4 As a result, there may be less frequent follow-up visits. It is important to monitor for early signs of relapse.

EXTENSIVE-STAGE: CHEMOTHERAPY AND RADIOTHERAPY

  • Combination chemotherapy with immunotherapy is recommended for eligible patients with ES-SCLC1,4,a

Initial Treatment Options for ES-SCLC1,7

Small Cell Lung Cancer (SCLC) Chemotherapy Drawing

COMBINATION CHEMOTHERAPY + IMMUNOTHERAPY

Use in
ES-SCLC

Systemic therapy:
  • Platinum agent plus etoposide plus immunotherapy4,a
About chemotherapy:
  • Standard duration: 4-6 cycles
  • For patients who respond with at least disease control:
    • Continue with immunotherapy alone until:
      • Disease progression
      • Unacceptable toxicity

Efficacy and Safety Results

Platinum-based chemotherapy plus immunotherapy
  • Significantly increased median OS
  • Improved PFS rates
Small Cell Lung Cancer (SCLC) Radiotherapy Drawing

RADIOTHERAPY

Use in
ES-SCLC

If patients respond to initial treatment, radiation to the chest may be given
  • Typically reserved for palliation, including painful bone metastases

Efficacy and Safety Results

May improve OS rates
Brain Drawing

PROPHYLACTIC CRANIAL IRRADIATION (PCI)b

Use in
ES-SCLC

Controversial in this context:

Recent randomized phase 3 data suggest limited or no patient benefit

Efficacy and Safety Results

N/A

PFS=progression-free survival.

aSee the NCCN Guidelines® for SCLC for detailed recommendations.

bCurrent randomized trials are evaluating whether brain MRI surveillance alone is non-inferior to MRI surveillance plus PCI on overall survival.4

As with any medical therapy, it is essential to weigh the risks and benefits of available treatments for SCLC.1 After relapse, you should choose the appropriate treatment option for your patient.1,4



Discover FDA-approved
treatments for SCLC

►

ASSESSMENT, SURVEILLANCE, AND SECOND-LINE TREATMENT

Response Assessment Is an Important Aspect of Patient Management4

LS-SCLC

ES-SCLC

After adjuvant chemotherapy alone or chemotherapy with concurrent RT for patients with LS-SCLC, response assessment using CT with contrast of the chest/abdomen/pelvis should occur only after completion of therapy; repeating CT scans during therapy is not recommended4

For systemic therapy alone or sequential systemic therapy followed by RT in patients with LS-SCLC, response assessment using CT with contrast of the chest/abdomen/pelvis should occur after every 2 to 3 cycles of systemic therapy, and again at completion of therapy4

During systemic therapy for patients with ES-SCLC, response assessment using CT with contrast of the chest/abdomen/pelvis should occur after every 2 to 3 cycles of systemic therapy4
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Frequency of follow-up depends on4:

  • Disease stage
  • Response to treatment (partial or complete, stable disease)

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Since relapse is highly likely1,8:

  • Schedule time for routine monitoring
  • Offer salvage treatment if appropriate

RT=radiotherapy.

FREQUENCY OF FOLLOW-UP VISITS IS DEPENDENT ON DISEASE STAGE

For Complete Response/Partial Response/Stable Disease4

LIMITED STAGE

After completion of initial therapy
  • Every 3 months during years 1-2
  • Every 6 months during year 3
  • Then annually

EXTENSIVE STAGE

After completion of initial
or subsequent therapy
  • Every 2 months during year 1
  • Every 3-4 months during years 2-3
  • Every 6 months during years 4-5
  • Then annually
  • NCCN Guidelines recommend follow-up visits. At each such visit:
    • A history, physical exam, and CT scans of the chest ± abdomen/pelvis are recommended4
    • Brain MRI (preferred) or CT is typically performed every 3-4 months during year 1 and every 6 months during year 24
  • Patient follow-up should also include the management of the multiple comorbidities often associated with the disease, including cardiac and respiratory comorbidities1
    • This may provide better symptom control, and possibly, better patient outcomes1

SCLC has poor prognosis due to high relapse rates. It is important to evaluate optimal therapy.1,4

NCCN=National Comprehensive Cancer Network® (NCCN®).

    REFERENCES:
  1. Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021;7(1):3. doi:10.1038/s41572-020-00235-0
  2. Reck M, Mok TSK, Mansfield A, et al. Brief report: exploratory analysis of maintenance therapy in patients with extensive-stage SCLC treated first line with atezolizumab plus carboplatin and etoposide. J Thorac Oncol. 2022;17(9):1122-1129. doi:10.1016/j.jtho.2022.05.016
  3. Shaw J, Pundole X, Balasubramanian A, et al. Recent treatment patterns and real-world survival following first-line anti-PD-L1 treatment for extensive-stage small cell lung cancer. Oncologist. 2024;29(12):1079-1089. doi:10.1093/oncolo/oyae234
  4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Small Cell Lung Cancer V.4.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed March 25, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  5. Cramer-van der Welle CM, Schramel FMNH, van Leeuwen AS, Groen HJM, van de Garde EMW; Santeon SCLC Study Group. Real-world treatment patterns and outcomes of patients with extensive disease small cell lung cancer. Eur J Cancer Care (Engl). 2020;29(5):e13250. doi:10.1111/ecc.13250
  6. Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomized, superiority trial. Lancet Oncol. 2017;18(8):1116-1125. doi:10.23937/2378-3419/1410111
  7. 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;18(5):663-671.
  8. Alvarado-Luna G, Morales-Espinosa D. Treatment for small cell lung cancer, where are we now? – a review. Transl Lung Cancer Res. 2016;5(1):26-38.