Lung%20cancer Treatment

• Neoadjuvant or adjuvant therapy, given concurrently with radiation therapy depending on the disease stage, is recommended for high-risk patients with stage IB-IIIA
• Cisplatin-based regimens (Cisplatin plus either Vinorelbine, Etoposide, Gemcitabine, Docetaxel, or Pemetrexed) are recommended
  • Cisplatin + Pemetrexed combination is preferred in patients with non-squamous NSCLC and combination with Gembitabine or Docetaxel is preferred in patients with squamous NSCLC
• Carboplatin-based regimens (Carboplatin plus either Paclitaxel, Gemcitabine or Pemetrexed) are recommended for patients with comorbidities or with contraindications to Cisplatin therapy
• Treatment with Osimertinib may be considered in patients with completely resected stage IIB-IIIA or high risk stage IB-IIA EGFR mutation-positive NSCLC ineligible for platinum-based chemotherapy or with previous adjuvant chemotherapy
• Atezolizumab may be considered in patients with completely resected stage IIB–IIIA or high-risk IIA PD-L1 ≥1% NSCLC with previous adjuvant chemotherapy

Chemotherapeutic Regimens Used with Radiation Therapy

• Carboplatin/Cisplatin + Pemetrexed, Paclitaxel + Carboplatin, and Cisplatin + Etoposide combination therapy with concurrent thoracic radiotherapy are the preferred regimens for patients with non-squamous cell NSCLC
• Paclitaxel + Carboplatin and Cisplatin + Etoposide combination therapy with concurrent thoracic radiotherapy are the preferred regimens for patients with squamous cell NSCLC
• Efficacy rates are better in patients given concurrent chemoradiation therapy compared to those given chemotherapy after radiation therapy

Consolidation Therapy

• Durvalumab is recommended by the NCCN as consolidation therapy for patients with PS 0-1 with unresectable stage III NSCLC who were deemed responsive to ≥2 cycles of chemoradiation therapy

• Recommended in patients with advanced, metastatic, or high-risk early resectable disease [ie high risk stage IB patients (with poorly defined tumors, vascular invasion, wedge resection, minimal margins, >4 cm tumor, visceral pleural involvement, and regional LN that cannot be assessed) with negative nodal margin, stage IB patients with positive nodal margin, or patients with stage IIA, IIIA, IIIB, or IV irregardless of nodal margin status]
• Selection of systemic therapy is based on the histology of NSCLC
  
  • Histologic subtype and molecular testing should be determined before therapy so that the best treatment can be selected

• Targeted therapy is potentially very effective in patients with specific gene mutations or rearrangements, and in patients with metastatic disease
• Platinum-based chemotherapy lengthens survival, improves symptom control and offers better quality of life

First-line Therapy

• Osimertinib is the preferred 1st-line therapy option for epidermal growth factor receptor (EGFR) mutation-positive patients with advanced, recurrent, or metastatic non-squamous NSCLC adenocarcinoma
  • Alternative therapy to Osimertinib include Erlotinib, Afatinib, Gefitinib, Dacomitinib and Erlotinib + Ramucirumab/Bevacizumab or its biosimilar
  • Combination of Erlotinib with Bevacizumab or its biosimilar may be considered in patients with non-squamous NSCLC without recent history of hemoptysis
• If mutation was discovered during 1st-line chemotherapy, may opt to continue with the present treatment or may interrupt, or may be followed by another regimen of Osimertinib 
  • May also consider treatment with Erlotinib or Afatinib or Gefitinib or Dacomitinib or Erlotinib + Ramucirumab/Bevacizumab or its biosimilar

• Afatinib and Osimertinib are the preferred 1st-line therapy options for EGFR S768I, L861Q, and/or G719X mutation-positive NSCLC patients
  • Alternative agents include Erlotinib, Gefitinib, and Dacomitinib
• If mutation was discovered during 1st-line chemotherapy, may opt to continue with the present treatment or may interrupt, or may be followed by another regimen of Afatinib or Osimertinib
  • May also consider treatment with Erlotinib or Gefitinib or Dacomitinib

• Initial treatments used for adenocarcinoma and squamous cell carcinoma may also be used as a 1st-line therapy

• Initial treatments used for adenocarcinoma and squamous cell carcinoma may also be used as a 1st-line therapy

• Alectinib, Brigatinib and Lorlatinib are the preferred agents among the 1st-line therapy options for patients with metastatic NSCLC positive for ALK rearrangement
• Ceritinib and Crizotinib are 1st-line therapy options for locally advanced or metastatic ALK rearrangement-positive NSCLC 
• If mutation was discovered during 1st line chemotherapy, may opt to continue with the present treatment or may interrupt, or may be followed by another regimen of Alectinib or Brigatinib or Lorlatinib or Crizotinib or Ceritinib
• Studies showed that patients given Crizotinib have very high response rates and significantly improved symptoms like pain, dyspnea or cough, as well as improved survival rates
  • May be used for NSCLC patients with PS 0-4
  • May cause few side effects (eg increase in aminotransferase) or rare life-threatening pneumonitis
  • Also targets ROS1 gene rearrangements and MET amplification

• Crizotinib or Entrectinib are preferred1st-line therapy options for ROS1 rearrangement-positive NSCLC 
• Ceritinib is used as a 1st-line therapy option for patients not given Crizotinib
  
  • Studies showed that ROS1 rearrangement-positive NSCLC patients given Crizotinib produce high response rates (70-80%)
• If mutation was discovered during 1st-line chemotherapy, may opt to continue with the present treatment or may interrupt, or may be followed by another regimen of Crizotinib or Entrectinib or Ceritinib

• Combination treatment with Dabrafenib plus Trametinib is preferred
• Monotherapy with Vemurafenib, Dabrafenib, or initial treatments used for adenocarcinoma and squamous cell carcinoma may also be used as 1st-line therapy
• If mutation was discovered during 1st-line chemotherapy, may opt to continue with the present treatment or may interrupt, followed by Dabrafenib + Trametinib therapy

• Larotrectinib or Entrectinib or 1st-line treatments for adenocarcinoma and squamous cell carcinoma are the preferred 1st-line therapy options for NTRK1/2/3 gene fusion-positive NSCLC
• If gene fusion was discovered during 1st-line chemotherapy, may opt to continue with the present treatment or may interrupt, or may be followed by another regimen of Larotrectinib or Entrectinib

• Capmatinib or Tepotinib are preferred 1st-line therapy options for patients with METex14 skipping mutation-positive NSCLC
  • Crizotinib and initial treatments used for adenocarcinoma and squamous cell carcinoma may also be used as a 1st-line therapy options
• If mutation was discovered during 1st-line chemotherapy, may opt to continue with the present treatment or may interrupt, or may be followed by Capmatinib or Tepotinib or Crizotinib

• Selpercatinib and Pralsetinib are preferred 1st-line therapy options for patients with RET rearrangement-positive NSCLC
  • Cabozantinib or initial treatments used for adenocarcinoma and squamous cell carcinoma may also be used as 1st-line therapy options
• If mutation was discovered during 1st-line chemotherapy, may opt to continue with the present treatment or may interrupt, or may be followed by Selpercatinib or Pralsetinib or Cabozantinib

• Pembrolizumab monotherapy or (Carboplatin or Cisplatin) + Pemetrexed + Pembrolizumab or Atezolizumab or Cemiplimab-rwlc are the preferred therapy options for PD-L1 expression-positive (≥50%) adenocarinoma, large cell NSCLC NOS patients negative for actionable molecular markers without contraindications to PD-L1/PD-1 inhibitors
  • Studies showed that PD-L1 expression-positive NSCLC patients given Pembrolizumab produce high response rates with less treatment-related adverse reactions
  • Other recommended 1st-line regimens include Carboplatin + Paclitaxel + Bevacizumab + Atezolizumab, Carboplatin + albumin-bound Paclitaxel + Atezolizumab, and Nivolumab + Ipilimumab + Pemetrexed +(Carboplatin or Cisplatin)
  • Nivolumab + Ipilimumab may be considered in patients with high tumor mutational burden
• Pembrolizumab or Carboplatin + (Paclitaxel or albumin-bound Paclitaxel) + Pembrolizumab or Atezolizumab or Cemiplimab-rwlc are the preferred therapy options for PD-L1 expression-positive (≥50%) squamous cell carcinoma patients negative for actionable molecular markers without contraindications to PD-L1/PD-1 inhibitors
  • Other recommended 1st-line regimens include Nivolumab + Ipilimumab + Paclitaxel + Carboplatin and Nivolumab + Ipilimumab (patients with high tumor mutational burden)
• May proceed to maintenance treatment with Pembrolizumab, Pembrolizumab + Pemetrexed, Atezolizumab with or without Bevacizumab, Cemiplimab-rwlc or Nivolumab + Ipilimumab in patients with adenocarcinoma if with stable disease or adequate treatment response, depending on initial treatment
• May proceed to maintenance treatment with Pembrolizumab, Atezolizumab, Cemiplimab-rwlc or Nivolumab + Ipilimumab in patients with squamous cell carcinoma if with stable disease or adequate treatment response, depending on initial treatment
• Immunohistochemistry (IHC) testing for PD-L1 expression may be done prior to initiation of therapy 

• (Carboplatin or Cisplatin) + Pemetrexed + Pembrolizumab is the preferred 1st-line therapy for PD-L1 expression-positive (≥1-49%) adenocarcinoma, large cell NSCLC NOS patients negative for actionable molecular markers without contraindications to PD-L1/PD-1 inhibitors
  • Carboplatin + Paclitaxel + Bevacizumab + Atezolizumab, Carboplatin + albumin-bound Paclitaxel + Atezolizumab, Nivolumab + Ipilimumab + Pemetrexed + (Carboplatin/Cisplatin), Nivolumab + Ipilimumab combination therapies and Pembrolizumab monotherapy may also be considered
• Carboplatin + (Paclitaxel or albumin-bound Paclitaxel) + Pembrolizumab is the preferred therapy for PD-L1 expression-positive (≥1-49%) squamous cell carcinoma patients negative for actionable molecular markers without contraindications to PD-L1/PD-1 inhibitors
  • Nivolumab + Ipilimumab + Paclitaxel + Carboplatin, Nivolumab/Ipilimumab combination therapy and Pembrolizumab monotherapy may also be considered in certain circumstances
• May proceed to maintenance treatment with Pembrolizumab, Pembrolizumab + Pemetrexed, Atezolizumab with or without Bevacizumab, or Nivolumab + Ipilimumab in patients with adenocarcinoma if with stable disease or adequate treatment response, depending on initial treatment
• May proceed to maintenance treatment with Pembrolizumab or Nivolumab + Ipilimumab in patients with squamous cell carcinoma if with stable disease or adequate treatment response, depending on initial treatment
• Systemic therapy used for adenocarcinoma and squamous cell carcinoma may be used for disease progression despite continuation maintenance therapy
• Immunohistochemistry (IHC) testing for PD-L1 expression may be done prior to initiation of therapy

• Consider 1st-line treatments for PD-L1 expression-positive (<1%) adenocarcinoma, large cell NSCLC NOS or squamous cell carcinoma patients negative for actionable molecular markers without contraindications to PD-L1/PD-1 inhibitors

• Pembrolizumab + Pemetrexed + Carboplatin or Cisplatin combination is the preferred regimen if without contraindications to Pembrolizumab
• Atezolizumab + Carboplatin  + Paclitaxel + Bevacizumab, Atezolizumab + Carboplatin + albumin-bound Paclitaxel, Nivolumab + Ipilimumab + Pemetrexed + (Carboplatin or Cisplatin), or Nivolumab + Ipilimumab combination may be used
• Bevacizumab-based regimens (Bevacizumab + Pemetrexed + Carboplatin or Cisplatin, Bevacizumab + Carboplatin + Paclitaxel) are only recommended for patients with adenocarcinoma, large cell, NSCLC NOS
  • Criteria for receiving Bevacizumab + chemotherapy: Non-squamous NSCLC and absence of hemoptysis
  • Bevacizumab should be given until disease progression but should be used cautiously in patients with risk of thrombocytopenia and bleeding
• Carboplatin-based combinations (Carboplatin plus either albumin-bound Paclitaxel, Docetaxel, Etoposide, Gemcitabine, Paclitaxel, or Pemetrexed)) are recommended for patients intolerant to Cisplatin and Pembrolizumab combination therapy regimens and those with comorbidities
  • Albumin-bound Paclitaxel combined with Carboplatin for patients with advanced NSCLC with PS 0-1 is preferred by the NCCN panel over standard Paclitaxel due to its lesser neurotoxicity and better response rate
• Cisplatin-based combinations (Cisplatin plus either Paclitaxel, Docetaxel, Gemcitabine, Etoposide, or Pemetrexed) are recommended for patients with non-squamous and squamous cell NSCLC with PS of 0-1 
• Gemcitabine-based combinations (Gemcitabine + Docetaxel or Vinorelbine) are recommended for patients with contraindications to platinum-based doublets
• Platinum-based regimens have been shown superior in patients with advanced and non-treatable disease with 6-12 weeks improvement in median survival and 10-15% improvement in 1-year survival rates

Recommended Regimens for Adenocarcinoma, Large Cell, NSCLC NOS (Advanced or Metastatic NSCLC or NSCLC NOS) with PS 2 without Druggable Targets    

• Single agent therapy or platinum-based combination regimens are alternative treatment options for patients with PS 2 with advanced/metastatic NSCLC
  • Recommended monotherapies include Gemcitabine, Pemetrexed, or taxanes (eg Docetaxel, albumin-bound and standard Paclitaxel)
  • Carboplatin-based combinations (Carboplatin + albumin-bound Paclitaxel, Docetaxel, Etoposide, Gemcitabine, Paclitaxel, or Pemetrexed) and Gemcitabine-based combinations (Gemcitabine + Docetaxel or Vinorelbine) are alternative therapeutic options

• Pembrolizumab + Carboplatin + Paclitaxel or albumin-bound Paclitaxel combinations are the preferred options if without contraindications to Pembrolizumab
• Nivolumab + Ipilimumab or Nivolumab + Ipilimumab + Paclitaxel + Carboplatin combination may also be considered
• Carboplatin-based combinations (Carboplatin plus either albumin-bound Paclitaxel, Docetaxel, Gemcitabine, or Paclitaxel) are recommended for patients intolerant to Cisplatin and Pembrolizumab combination therapy regimens and those with comorbidities
  • Combination with albumin-bound Paclitaxel, Docetaxel, Gemcitabine, or Paclitaxel may be used
  • Albumin-bound Paclitaxel combined with Carboplatin for patients with advanced NSCLC with PS 0-1 is preferred by the NCCN panel over standard Paclitaxel due to its lesser neurotoxicity and better response rate
• Cisplatin-based combinations (Cisplatin plus either Paclitaxel, Docetaxel, Gemcitabine, or Etoposide) are recommended for patients with PS of 0-1
  • Cisplatin + Pemetrexed regimen has been shown more effective and with reduced toxicity as compared with Cisplatin + Gemcitabine regimen; Cisplatin + Gemcitabine has superior efficacy in patients with squamous histology compared to Cisplatin + Pemetrexed
• Gemcitabine-based combinations (Gemcitabine + Docetaxel or Vinorelbine) are recommended for patients with contraindications to platinum-based doublets
• Platinum-based regimens have been shown superior in patients with advanced and non-treatable disease, with 6-12 weeks improvement in median survival and 10-15% improvement in 1-year survival rate 

• Single agent therapy or platinum-based combination regimens are alternative treatment options for patients with PS 2 with advanced/metastatic NSCLC
  • Recommended monotherapies include Gemcitabine, or taxanes (eg Docetaxel, albumin-bound and standard Paclitaxel)
  • Carboplatin-based combinations (Carboplatin + albumin-bound Paclitaxel, Docetaxel, Etoposide, Gemcitabine, or Paclitaxel) and Gemcitabine-based combinations (Gemcitabine + Docetaxel or Vinorelbine) are alternative therapeutic options

Subsequent Therapy

• For patients with disease progression despite Osimertinib therapy, may continue treatment with Osimertinib if asymptomatic or symptomatic only if the lesion is located in the brain or with an isolated systemic lesion; if with multiple lesions, may consider systemic therapy options for adenocarcinoma or squamous cell carcinoma
• For asymptomatic patients positive for T790M mutation, may initiate Osimertinib treatment; may continue present therapy with Erlotinib (with or without Ramucirumab or Bevacizumab) or Afatinib or Gefitinib or Dacomitinib therapy if T790M mutation-negative
• For symptomatic patients positive for T790M mutation and with brain metastasis, may initiate Osimertinib treatment or may continue present therapy with Erlotinib (with or without Ramucirumab or Bevacizumab) or Afatinib or Gefitinib or Dacomitinib therapy if T790M mutation-negative
  • May consider Osimertinib in patients with progressive CNS or leptomeningeal disease, regardless of T790M status
• For symptomatic patients with systemic metastasis positive for T790M mutation but lesions are isolated, may opt to continue present therapy, continue Erlotinib (with or without Ramucirumab or Bevacizumab) or Afatinib or Gefitinib or Dacomitinib therapy if T790M mutation-negative
  • For oligoprogressive disease, continue same TKI with local ablative therapy (eg SBRT)
• For symptomatic patients with systemic metastasis positive for T790M mutation but with multiple lesions or with progressive disease despite chemotherapy, initiation of Osimertinib treatment (if Osimertinib-naive) may be considered
  • If T790M mutation negative, may consider treatment for adenocarcinoma or squamous cell carcinoma
• Afatinib + Cetuximab is an option for patients who progressed despite treatment with TKI and chemotherapy
• Combination of Erlotinib with Bevacizumab or its biosimilar may be considered in patients with non-squamous NSCLC if without any recent history of hemoptysis

• Management is the same as in patients with EGFR EXON 19 deletion or L858R mutations

• Recommended treatment options for patients with PS 0-2 with disease progression after 1st-line therapy include Amivantamab-vmjw and Mobocertinib
• If still with disease progression despite completion of Amivantamab-vmjw or Mobocertinib therapy, treatment using agents for adenocarcinoma and/or squamous cell carcinoma may be considered in patients with PS 0-2

• Sotorasib is the recommended treatment for patients with PS 0-2 with disease progression after 1st-line therapy
• If still with disease progression despite completion of Sotorasib therapy, treatment using agents for adenocarcinoma and/or squamous cell carcinoma may be considered in patients with PS 0-2

• May continue Crizotinib therapy, or may initiate Alectinib or Brigatinib or Ceritinib therapy, or may consider local therapy in asymptomatic patients with history of Crizotinib treatment
• For asymptomatic patients previously given Alectinib, Brigatinib, Ceritinib or Lorlatinib, may consider local therapy or may continue Alectinib or Brigatinib or Ceritinib or Lorlatinib therapy
• For symptomatic patients with brain involvement, may consider local therapy for limited lesions, or may initiate Ceritinib or Alectinib or Brigatinib therapy if Crizotinib was previously given, or may continue Alectinib or Brigatinib or Ceritinib or Lorlatinib therapy if previously given
  • If with disease progression despite subsequent treatment, consider initiation of Lorlatinib therapy or 1st line treatments for adenocarcinoma and squamous cell carcinoma
• For symptomatic patients with systemic involvement, may consider local therapy or may continue Crizotinib therapy in patients with isolated lesions previously given Crizotinib or may continue Alectinib or Brigatinib or Ceritinib or Lorlatinib therapy if previously given
  • If with disease progression despite subsequent treatment, consider initiation of Lorlatinib therapy or 1st-line treatments for adenocarcinoma and squamous cell carcinoma
• For symptomatic patients with systemic involvement but with multiple lesions, may initiate Ceritinib or Alectinib or Brigatinib therapy if Crizotinib was previously given, or may consider treatment for adenocarcinoma or squamous cell carcinoma
  • May consider treatment with Lorlatinib if still with disease progression despite treatment with Alectinib or Brigatinib or Ceritinib
• For symptomatic patients with systemic involvement but with limited metastases previously given Alectinib or Brigatinib or Ceritinib or Lorlatinib, may consider treatment with Lorlatinib if still with disease progression or Lorlatinib-naive; if with multiple lesions, may consider treatment with Lorlatinib if not given previously or may consider treatment for adenocarcinoma or squamous cell carcinoma

• Consider 1st line treatments for adenocarcinoma, and squamous cell carcinoma if disease progression occurs despite initial treatment with Dabrafenib + Trametinib, Dabrafenib monotherapy, or Vemurafenib therapy for treatment-naive patients, or 1st-line treatments for adenocarcinoma and/or squamous cell carcinoma if progression occurs during 1st-line systemic therapy
• Dabrafenib + Trametinib combination therapy may also be considered if disease progresses despite using 1st-line treatments for adenocarcinoma and/or squamous cell carcinoma

• For asymptomatic patients and symptomatic patients with limited metastases previously given Entrectinib, Crizotinib, or Ceritinib, may consider local therapy or may continue Entrectinib, Crizotinib, Ceritinib, or Lorlatinib therapy
• For symptomatic patients with brain involvement, may consider local therapy for limited lesions, or may initiate Entrectinib therapy if Crizotinib or Ceritinib was previously given
• If with disease progression despite subsequent treatment, consider 1st-line treatments for adenocarcinoma and squamous cell carcinoma
• For symptomatic patients with systemic involvement but with multiple lesions, may initiate Lorlatinib therapy if Entrectinib, Crizotinib, or Ceritinib was previously given, or may consider treatment for adenocarcinoma or squamous cell carcinoma

• Consider 1st-line treatments for adenocarcinoma and squamous cell carcinoma if disease progression occurs despite treatment with Larotrectinib or Entrectinib therapy
• Larotrectinib or Entrectinib therapy may also be considered if disease progresses despite using 1st-line treatments for adenocarcinoma and/or squamous cell carcinoma

• Consider 1st-line treatments for adenocarcinoma and squamous cell carcinoma if disease progression occurs despite treatment with Capmatinib, Tepotinib or Crizotinib
• Capmatinib or Tepotinib therapy may also be considered if disease progresses despite using 1st-line treatments for adenocarcinoma and/or squamous cell carcinoma
  • Crizotinib therapy may also be considered
• If mutation was discovered during 1st-line chemotherapy and disease progressed despite completion of 1st-line treatments, therapy using 1st-line agents for adenocarcinoma and/or squamous cell carcinoma may be considered

• Consider 1st-line treatments for adenocarcinoma and squamous cell carcinoma if disease progression occurs despite treatment with Selpercatinib, Pralsetinib, or Cabozantinib
• Selpercatinib or Pralsetinib therapy may also be considered if disease progresses despite using 1st-line treatments for adenocarcinoma and/or squamous cell carcinoma
  • Cabozantinib therapy may also be considered
• If mutation was discovered during 1st-line chemotherapy and disease progressed despite completion of 1st-line treatments, therapy using 1st-line agents for adenocarcinoma and/or squamous cell carcinoma may be considered

• For patients previously given anti-PD1 or anti-PD-L1 agents as 1st-line therapy, treatment with standard platinum doublet chemotherapy should be considered if a single agent immunotherapy was given, or standard 2nd-line options if combined chemo-immunotherapy as 1st-line therapy was used
  • Pembrolizumab may only be given in PD-L1 expression-positive patients

• Nivolumab, Pembrolizumab, and Atezolizumab are among the preferred therapy for patients with PS 0-2 with disease progression despite 1st-line systemic therapy if no prior exposure to anti-PD1/L1
• Docetaxel or Gemcitabine or Pemetrexed or albumin-bound Paclitaxel, or Ramucirumab + Docetaxel are indicated as 2nd-line or beyond therapy for patients with PS of 0-2
• Nintedanib + Docetaxel may be considered in patients with PS 0-2 and early disease progression (within 9 months after initiation of therapy)

• Nivolumab, Pembrolizumab, or Atezolizumab are indicated as preferred therapy for patients with PS 0-2
• Docetaxel or Gemcitabine or albumin-bound Paclitaxel or Ramucirumab + Docetaxel are indicated as 2nd-line or beyond therapy for patients with PS of 0-2

Maintenance Therapy

• Given after 4-6 cycles of chemotherapy for PS 0-2 patients with tumor response or disease that did not progress

Continuation Maintenance Therapy

• Utilizes at least 1 of the agents given as 1st-line treatment
• The following may be considered in patients with adenocarcinoma, large cell, NSCLC NOS negative for rearrangements or mutations
  • Monotherapy with Gemcitabine or Pemetrexed or Bevacizumab or Atezolizumab
  • Combination therapy with (Bevacizumab or Pembrolizumab) + Pemetrexed or Atezolizumab + Bevacizumab or Nivolumab + Ipilimumab
• For patients with squamous cell NSCLC negative for rearrangements or mutations, monotherapy with Pembrolizumab or Gemcitabine, or combination therapy with Nivolumab + Ipilimumab may be considered

Switch Maintenance Therapy

• Utilizes other agents not part of the 1st-line regimen
• Eg Pemetrexed, Docetaxel
  
  • Pemetrexed used after 1st-line chemotherapy showed advantage in progression-free and overall survival
  • Pemetrexed may be started after 4-6 cycles of 1st-line platinum-doublet chemotherapy in patients with histologies other than squamous cell carcinoma
  • Docetaxel may be started after 4-6 cycles of 1st-line platinum-doublet regimen in patients with squamous cell carcinoma

Postoperative Therapy

• Platinum-based chemotherapy is recommended for patients with PS of 0-1 who underwent complete resection for NSCLC stage II-IIIA

Investigational Agents for Genetic Alterations

• Ado-trastuzumab emtansine and Fam-trastuzumab deruxtecan-nxki are recommended for use in patients with metastatic ERBB2 (HER2) mutations

Initial Therapy

• Single-agent or combination chemotherapy may be used in managing patients with SCLC
• Eg Cisplatin/Carboplatin + Etoposide, Irinotecan + Cisplatin/Carboplatin, Carboplatin + Etoposide + Atezolizumab, Cisplatin/Carboplatin + Etoposide + Durvalumab
• Cisplatin + Etoposide is the preferred regimen for patients with LD SCLC
  • Dose of Cisplatin may be reduced or may be replaced with Carboplatin if not tolerated
• For patients with ED SCLC, preferred regimens include Carboplatin + Etoposide + Atezolizumab, Carboplatin + Etoposide + Durvalumab and Cisplatin + Etoposide + Durvalumab
  • Alternative regimens include Carboplatin/Cisplatin + Etoposide and Carboplatin/Cisplatin + Irinotecan 
• Etoposide + Cisplatin regimen is the most commonly used initial combination chemotherapy in both limited disease (LD) and extensive disease (ED)
  
  • More effective and less toxic than alkylator + anthracycline-based regimens
  • Simultaneous use with thoracic radiotherapy is the recommended management for patients with LD but causes increased risk of esophagitis and pulmonary toxicity

• Carboplatin may be substituted to Cisplatin to decrease vomiting, neuropathy and nephropathy
  
  • Should only be given to patients with LD if Cisplatin is poorly tolerated or contraindicated

• Maintenance or consolidation chemotherapy used beyond the standard 4-6 cycles produced minimal prolongation of duration of response without improvement in survival and poses greater risk of toxicity
  • Agents used for maintenance therapy in ED SCLC patients include Atezolizumab and Durvalumab, to be based on what was used during treatment initiation

Subsequent Therapy

• Provides important palliation in patients with SCLC but the effect depends on the time from initial therapy to relapse
• If the interval is <3 month, effect of regimen is ≤10%, which indicates a refractory SCLC; if >3 months, expected effect is approximately 25%
• Bendamustine, Cyclophosphamide + Doxorubicin + Vincristine (CAV), Docetaxel, Etoposide (oral), Gemcitabine, Irinotecan, Lurbinectedin, Nivolumab, Temozolomide, Topotecan, Paclitaxel, Pembrolizumab, and Vinorelbine are treatment options in patients with PS of 0-2 that has disease that relapsed in ≤6 months
  • Topotecan and Lurbinectedin are the preferred agents for subsequent therapy
  • Immune checkpoint inhibitors (eg Nivolumab, Pembrolizumab) should not be used if there is disease progression during maintenance therapy with Atezolizumab or Durvalumab
• In patients that has disease that relapsed for >6 months, the original regimen should be used, or Lurbinectedin may be given