2026 NCCN Guidelines

2026 NCCN Guidelines

Lurbinectedin (ZEPZELCA®) + atezolizumab is a preferred option for patients whose disease has not progressed after first-line induction therapy1

National Comprehensive Cancer Network® (NCCN®) Preferred Regimen*

Lurbinectedin (ZEPZELCA) + atezolizumab is recommended as a maintenance therapy option for select patients with ES-SCLC after 4 cycles of carboplatin + etoposide + atezolizumab†

PRIMARY THERAPY FOR EXTENSIVE STAGE SCLCa

Four cycles of cytotoxic chemotherapy are recommended, but some patients may receive up to 6 cycles based on response and tolerability after 4 cycles

Preferred
  • Carboplatin AUC 5 Day 1 and Etoposide 100 mg/m2 Days 1, 2, 3 and Atezolizumab 1200 mg Day 1 every 21 Days x 4 cycles followed by maintenance Atezolizumab 1200 mg Day 1, every 21 Days (category 1 for all)b,c,d
  • Carboplatin AUC 5 Day 1 and Etoposide 100 mg/m2 Days 1, 2, 3 and Atezolizumab 1200 mg Day 1 every 21 Days x 4 cycles followed by maintenance Atezolizumab 1680 mg Day 1, every 28 Daysb,c,d
  • Carboplatin AUC 5 Day 1 and Etoposide 100 mg/m2 Days 1, 2, 3 and Atezolizumab 1200 mg Day 1 every 21 Days x 4 cycles followed by maintenance Lurbinectedin 3.2 mg/m2 and Atezolizumab 1200 mg Day 1, every 21 Dayse,f
  • Carboplatin AUC 5–6 Day 1 and Etoposide 80–100 mg/m2 Days 1, 2, 3 and Durvalumab 1500 mg Day 1 every 21 Days x 4 cycles followed by maintenance Durvalumab 1500 mg Day 1 every 28 Days (category 1 for all)b,c,g
  • Cisplatin 75–80 mg/m2 Day 1 and Etoposide 80–100 mg/m2 Days 1, 2, 3 and Durvalumab 1500 mg Day 1 every 21 Days x 4 cycles followed by maintenance Durvalumab 1500 mg Day 1 every 28 Days (category 1 for all)b,c,g
Other Recommended
Useful in Certain Circumstances
  • Carboplatin AUC 5–6 Day 1 and Etoposide 100 mg/m2 Days 1, 2, 3
  • Cisplatin 75 mg/m2 Day 1 and Etoposide 100 mg/m2 Days 1, 2, 3
  • Cisplatin 80 mg/m2 Day 1 and Etoposide 80 mg/m2 Days 1, 2, 3
  • Cisplatin 25 mg/m2 Days 1, 2, 3 and Etoposide 100 mg/m2 Days 1, 2, 3
  • Carboplatin AUC 5 Day 1 and Irinotecan 50 mg/m2 Days 1, 8, 15
  • Cisplatin 60 mg/m2 Day 1 and Irinotecan 60 mg/m2 Days 1, 8, 15
  • Cisplatin 30 mg/m2 Days 1, 8 and Irinotecan 65 mg/m2 Days 1, 8
Other Recommended
  • Carboplatin AUC 5–6 Day 1 and Etoposide 100 mg/m2 Days 1, 2, 3
  • Cisplatin 75 mg/m2 Day 1 and Etoposide 100 mg/m2 Days 1, 2, 3
  • Cisplatin 80 mg/m2 Day 1 and Etoposide 80 mg/m2 Days 1, 2, 3
  • Cisplatin 25 mg/m2 Days 1, 2, 3 and Etoposide 100 mg/m2 Days 1, 2, 3
Useful in Certain Circumstances
  • Carboplatin AUC 5 Day 1 and Irinotecan 50 mg/m2 Days 1, 8, 15
  • Cisplatin 60 mg/m2 Day 1 and Irinotecan 60 mg/m2 Days 1, 8, 15
  • Cisplatin 30 mg/m2 Days 1, 8 and Irinotecan 65 mg/m2 Days 1, 8

Note: All recommendations are category 2A unless otherwise indicated.

aFor transformation to SCLC from NSCLC, consider referral to a center with expertise.

bContraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or concurrent use of immunosuppressive agents. If TKI is continued, ICI should be avoided, due to known toxicity.

cMaintenance immunotherapy with either atezolizumab or durvalumab should continue until progression or intolerable toxicity.

dAtezolizumab and hyaluronidase-tqjs subcutaneous injection may be substituted for IV atezolizumab. Atezolizumab and hyaluronidase-tqjs has different dosing and administration instructions compared to atezolizumab for intravenous infusion.

eConsider adding lurbinectedin to maintenance atezolizumab in patients who have achieved at least stable disease following four cycles of induction chemoimmunotherapy, have an ECOG performance status of 0–1, and no history of brain metastases.

fThis regimen is not for use as re-treatment in subsequent line therapy if lurbinectedin has been used previously.

gIncluded patients with asymptomatic untreated brain metastases.

*Preferred interventions are based on superior efficacy, safety, and evidence, and, when appropriate, affordability.

†See the NCCN Guidelines for SCLC for detailed recommendations, including other treatment options.

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.

1LM=first-line maintenance; 2L=second line; AUC=area under the curve; ECOG=Eastern Cooperative Oncology Group; ES-SCLC=extensive-stage small cell lung cancer; ICI= immune checkpoint inhibitor; IV=intravenous; NCCN=National Comprehensive Cancer Network® (NCCN®); NSCLC=non-small cell lung cancer; PD-1=programmed death protein 1; PD-L1=programmed death ligand 1; SCLC=small cell lung cancer; TKI=tyrosine kinase inhibitor.

2026 NCCN Guidelines

Lurbinectedin (ZEPZELCA®) is a preferred option for SCLC subsequent systemic therapy1

NCCN Category 2A Preferred Recommendation*†

Lurbinectedin (ZEPZELCA) is recommended as a preferred subsequent systemic SCLC treatment option for patients who have not previously received lurbinectedin‡§

SCLC Subsequent Systemic Therapy (PS 0–2)a

Consider dose reduction or growth factor support for patients with PS 2

Preferred
  • Tarlatamab-dlleb (category 1)
  • Clinical trial enrollment
  • Irinotecanc
  • Lurbinectedin (if not previously used)
  • If prolonged disease-free time, re-treatment with platinum-based doublet with or without immunotherapy
  • Topotecan Oral (PO) or Intravenous (IV)
Other Recommended
  • CAV (Cyclophosphamide/Doxorubicin/Vincristine)
  • Docetaxel
  • Gemcitabine
  • Nivolumabd or Pembrolizumab (if not previously treated with an ICI)e
  • Oral Etoposide
  • Paclitaxel
  • Temozolomide

Note: All recommendations are category 2A unless otherwise indicated.

aSubsequent systemic therapy refers to second-line and beyond therapy.

bFor extensive stage with disease progression on or after platinum-based chemotherapy.

cFor patients with CNS disease, consider using irinotecan.

dNivolumab and hyaluronidase-nvhy subcutaneous injection may be substituted for IV nivolumab. Nivolumab and hyaluronidase-nvhy has different dosing and administration instructions compared to IV nivolumab.

eContraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or concurrent use of immunosuppressive agents. If TKI is continued, ICI should be avoided, due to known toxicity.

*Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus (≥85% support of the Panel) that the intervention is appropriate.

†Preferred interventions are based on superior efficacy, safety, and evidence, and, when appropriate, affordability.1

‡Subsequent systemic therapy refers to second-line and beyond therapy.1

§See the NCCN Guidelines for SCLC for detailed recommendations, including other treatment options.

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.

1LM=first-line maintenance; 2L=second line; CNS=central nervous system; ICI=immune checkpoint inhibitor; IV=intravenous; NCCN=National Comprehensive Cancer Network® (NCCN®); PD-1=programmed cell death protein 1; PD-L1=programmed death-ligand 1; PS=performance status; SCLC=small cell lung cancer; TKI=tyrosine kinase inhibitor.

Brochure for Healthcare Providers

Brochure for Healthcare Providers

Key details about ZEPZELCA + atezolizumab, including efficacy results, safety profile, recommended dosage, and more.

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Efficacy Data

See the data behind ZEPZELCA + atezolizumab in the IMforte clinical trial.

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Efficacy Data

See ZEPZELCA overall response and duration of response data in second-line therapy.

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INDICATIONS

ZEPZELCA (lurbinectedin) for injection 4 mg, in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, is indicated for the maintenance treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide.

ZEPZELCA (lurbinectedin) for injection 4 mg, as a single agent, is indicated for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Myelosuppression

ZEPZELCA can cause severe and fatal myelosuppression including febrile neutropenia and sepsis, thrombocytopenia and anemia.

Administer ZEPZELCA only to patients with baseline neutrophil count of at least 1,500 cells/mm3 and platelet count of at least 100,000/mm3. To reduce the risk of febrile neutropenia during treatment with ZEPZELCA in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, administer granulocyte colony-stimulating factor (G-CSF). Monitor blood counts including neutrophils, red blood cells and platelets prior to each ZEPZELCA administration. For neutrophil count less than 500 cells/mm3 or any value less than lower limit of normal, the use of G-CSF is recommended. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.

  • ZEPZELCA with Intravenous Atezolizumab
    • In the IMforte study, primary prophylaxis of G-CSF was administered to 84% of patients. Based on laboratory values, decreased neutrophils occurred in 36%, including 18% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased neutrophil cells was 31 days and a median duration of 10 days. Febrile neutropenia occurred in 1.7%. Sepsis occurred in 1%. There were 7 fatal infections: pneumonia (n=3), sepsis (n=3), and febrile neutropenia (n=1).
    • Based on laboratory values, decreased platelets occurred in 54%, including 15% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased platelet cells was 31 days and a median duration of 12 days.
    • Based on laboratory values, decreased hemoglobin occurred in 51%, including 13% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. The median time to onset of Grade 3 and 4 decreased hemoglobin was 64 days and a median duration of 8 days.
  • ZEPZELCA as a Single-Agent
    • In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA as a single agent, Grade 3 or 4 neutropenia occurred in 41% of patients, with a median time to onset of 15 days and a median duration of 7 days. Febrile neutropenia occurred in 7% of patients. Sepsis occurred in 2% of patients and was fatal in 1% (all cases occurred in patients with solid tumors other than SCLC). Grade 3 or 4 thrombocytopenia occurred in 10%, with a median time to onset of 10 days and a median duration of 7 days. Grade 3 or 4 anemia occurred in 17% of patients.

Hepatotoxicity

ZEPZELCA can cause hepatotoxicity which may be severe.

Monitor liver function tests prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.

  • ZEPZELCA with Intravenous Atezolizumab
    • In the IMforte study, based on laboratory values, increased alanine aminotransferase (ALT) occurred in 25%, including 3% Grade 3 or Grade 4 in patients who received ZEPZELCA in combination with atezolizumab. Increased aspartate aminotransferase (AST) occurred in 24% including 3% Grade 3 or Grade 4. The median time to onset of Grade ≥3 elevation in transaminases was 52 days (range: 6 to 337).
  • ZEPZELCA as a Single-Agent
    • In clinical studies of 554 patients with advanced solid tumors receiving ZEPZELCA as a single agent, Grade 3 elevations of ALT and AST were observed in 6% and 3% of patients, respectively, and Grade 4 elevations of ALT and AST were observed in 0.4% and 0.5% of patients, respectively. The median time to onset of Grade ≥3 elevation in transaminases was 8 days (range: 3 to 49), with a median duration of 7 days.

Extravasation Resulting in Tissue Necrosis

Extravasation of ZEPZELCA can cause skin and soft tissue injury, including necrosis requiring debridement. Consider use of a central venous catheter to reduce the risk of extravasation, particularly in patients with limited venous access. Monitor patients for signs and symptoms of extravasation during the ZEPZELCA infusion. If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis. The time to onset of necrosis after extravasation may vary.

  • ZEPZELCA with Intravenous Atezolizumab
    • In the IMforte study, extravasation resulting in skin necrosis occurred in one patient who received ZEPZELCA in combination with atezolizumab.

Administer supportive care and consult with an appropriate medical specialist as needed for signs and symptoms of extravasation. Administer subsequent infusions at a site that was not affected by extravasation.

Rhabdomyolysis

Rhabdomyolysis has been reported in patients treated with ZEPZELCA.

Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold or reduce the dose based on severity.

  • ZEPZELCA with Intravenous Atezolizumab
    • In the IMforte study, among 235 patients who had a creatine phosphokinase laboratory evaluation, increased creatine phosphokinase occurred in 9% who received ZEPZELCA in combination with atezolizumab.

Embryo-Fetal Toxicity

ZEPZELCA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 4 months after the last dose.

Lactation

There are no data on the presence of ZEPZELCA in human milk, however, because of the potential for serious adverse reactions from ZEPZELCA in breastfed children, advise women not to breastfeed during treatment with ZEPZELCA and for 2 weeks after the last dose.

ADVERSE REACTIONS

  • ZEPZELCA with Intravenous Atezolizumab
    • Serious adverse reactions occurred in 31% of patients receiving ZEPZELCA in combination with atezolizumab. Serious adverse reactions occurring in >2% were pneumonia (2.5%), respiratory tract infections (2.1%), dyspnea (2.1%), and decreased platelet count (2.1%). Fatal adverse reactions occurred in 5% of patients receiving ZEPZELCA with atezolizumab including pneumonia (3 patients), sepsis (3 patients), cardio-respiratory arrest (2 patients), myocardial infarction (2 patients), and febrile neutropenia (1 patient).
    • The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received ZEPZELCA with atezolizumab were decreased lymphocytes (55%), decreased platelets (54%), decreased hemoglobin (51%), decreased neutrophils (36%), nausea (36%), and fatigue/asthenia (32%).
  • ZEPZELCA as a Single-Agent
    • Serious adverse reactions occurred in 34% of patients who received ZEPZELCA. Serious adverse reactions in ≥3% of patients included pneumonia, febrile neutropenia, neutropenia, respiratory tract infection, anemia, dyspnea, and thrombocytopenia.
    • The most common adverse reactions, including laboratory abnormalities, (≥20%) are leukopenia (79%), lymphopenia (79%), fatigue (77%), anemia (74%), neutropenia (71%), increased creatinine (69%), increased alanine aminotransferase (66%), increased glucose (52%), thrombocytopenia (37%), nausea (37%), decreased appetite (33%), musculoskeletal pain (33%), decreased albumin (32%), constipation (31%), dyspnea (31%), decreased sodium (31%), increased aspartate aminotransferase (26%), vomiting (22%), decreased magnesium (22%), cough (20%), and diarrhea (20%).

DRUG INTERACTIONS

Effect of CYP3A Inhibitors and Inducers

Avoid coadministration with a strong or a moderate CYP3A inhibitor (including grapefruit and Seville oranges) as this increases lurbinectedin systemic exposure which may increase the incidence and severity of adverse reactions to ZEPZELCA. If coadministration cannot be avoided, reduce the ZEPZELCA dose as appropriate.

Avoid coadministration with a strong CYP3A inducer as it may decrease systemic exposure to lurbinectedin, which may decrease the efficacy of ZEPZELCA.

GERIATRIC USE

  • ZEPZELCA with Intravenous Atezolizumab
    • Of the 242 patients with ES-SCLC treated with ZEPZELCA and atezolizumab in IMforte, 124 (51%) patients were 65 years of age and older, while 29 (12%) patients were 75 years of age and older. No overall differences in effectiveness were observed between older and younger patients. There was no overall difference in the incidence of serious adverse reactions in patients ≥65 years of age and patients <65 years of age (33% vs. 29%, respectively). There was a higher incidence of Grade 3 or 4 adverse reactions in patients ≥65 years of age compared to younger patients (45% vs. 31%, respectively).
  • ZEPZELCA as a Single-Agent
    • Of the 105 patients with SCLC administered ZEPZELCA in clinical studies, 37 (35%) patients were 65 years of age and older, while 9 (9%) patients were 75 years of age and older. No overall difference in effectiveness was observed between patients aged 65 and older and younger patients.
    • There was a higher incidence of serious adverse reactions in patients ≥65 years of age than in patients <65 years of age (49% vs. 26%, respectively). The serious adverse reactions most frequently reported in patients ≥65 years of age were related to myelosuppression and consisted of febrile neutropenia (11%), neutropenia (11%), thrombocytopenia (8%), and anemia (8%). There was a higher incidence of Grade 3 or 4 adverse reactions in patients ≥65 years of age compared to younger patients (76% vs. 50%, respectively).

HEPATIC IMPAIRMENT

Avoid administration of ZEPZELCA in patients with severe hepatic impairment. If administration cannot be avoided, reduce the dose. Monitor for increased adverse reactions in patients with severe hepatic impairment.

Reduce the dose of ZEPZELCA in patients with moderate hepatic impairment. Monitor for increased adverse reactions in patients with moderate hepatic impairment.

No dose adjustment of ZEPZELCA is recommended for patients with mild hepatic impairment.

Please see full Prescribing Information.

Reference: 1. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Small Cell Lung Cancer. V.2.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. The NCCN Guidelines® and illustrations therein may not be reproduced in any form for any purpose without express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.