Stage 4 lung cancer treatment

Written by:     Dr. Julfikar Saif
                     Bachelor of medicine Bachelor of Surgery
                     Bangladesh.

Non small cell lung cancer is a term that includes adenocarcinoma of lung, squamous cell carcinoma of lung and large cell carcinoma of lung. It is considered to be stage IV when already tumor spreading to distant location or metastasis has taken place. 

Effective treatment is few and far between. Most of the patients are only offered palliative treatment. But indeed some appropriately selected patient with very limited and localised spreading might be offered curative treatment. But this is few and far between. Chemotherapy is the mainstay of treatment with newer options including immunotherapy, monoclonal antibody and gene specific therapy. 

The first line of treatment includes chemotherapy with platinum based doublets. Agents include cisplatin or carboplatin with paclitaxel or docetaxel or gemcitabine or vinorelbine which are given in 4-6 cycles. Instead of using combinations only a single agent may be used in the elderly with good performance status for 4-6 cycles.

First line chemotherapy for squamous cell carcinoma includes paclitaxel protein bound with carboplatin or a regimen which includes the monoclonal antibody necitumumab with gemcitabine and cisplatin. If patient is eligible that means if they have a non-squamous cancer, no history of coughing up blood, single brain metastasis which is treated, can be treated with another monoclonal antibody Bevacizumab-based  regimens which includes different combinations of 1 or more traditional chemotherapeutic agents carboplatin, cisplatin, docetaxel, paclitaxel, gemcitabine and pemetrexed continued for 4-6 cycles and bevacizumab till disease progression occurs. 

If EGFR (epidermal growth factor receptor) immunehistochemistry is positive then regimen of cisplatin plus vinorelbine for 4-6 cyles with cetuximab another monoclonal antibody which will again be continued even after the cycles until disease progression occurs. Newer drugs for first line treatment of stage IV NSCLC in patients whose tumor EGFR exon 19 deletion or exon 21 substitution mutation have been FDA approved. 

They are the tyrosine kinase inhibitors erlotinib, afatinib, gefatinib which will be taken orally daily until disease progression occurs.

Treatment for anaplastic lymphoma kinase (ALK) positive stage IV tumor  is crizotinib which is an protein kinase inhibitor. If the patient is refractory or intolerant to crizotinib, certinib or alectinib can be used. 

Tumors with high PD-L1 expression [Tumor Proportion Score (TPS) ≥50%)] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor might be treated with monoclonal antibody pembrolizumab until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. If the patient responds then after 4-6 cycles of chemotherapy maintainance chemotherapy may be used until toxicity or disease progression occurs with increased survival and disease free interval noticed if the agent is switched to a different one.

When first line chemotherapeutics fail then second line chemotherapeutics are reccomended. The options include Nivolumab until disease progression or unacceptable toxicity or Docetaxel for 4-6 cycles with ramucirumab. Pembrolizumab until disease progression or unacceptable toxicity  in tumors that are PD-L1 positive; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving it. Erlotinib can be used in EGFR mutations and squamous NSCLC which progressed despite platinum based first line chemotherapy can be treated by afatinib. 

If disease further progresses then third line chemotherapeutics are used. Options include erlotinib for EGFR mutation or gene amplification, ramucirumab for EGFR or ALK-1 mutation , Pembrolizumab  for those tumors which express PDL1 and nivolumab for both squamous and non squamous NSCLC that progressed with platinum based chemotherapy.  But inspite of all these treatment modalities according to National Cancer Institute’s SEER database of USA the 5year survival of this stage stands at around 1% with median survival of 8months currently. Most of the regimens are still in clinical trial and patients are encouraged to attend these trials so that new headways can be made.