The National Comprehensive Cancer Network (NCCN) publishes annual clinical practice guidelines for various malignancies that are recognized and followed by clinicians worldwide. Recently released non-small cell lung cancer (NSCLC) guidelines, 2014 V4 edition, focuses on the section on systemic therapy for advanced or metastatic NSCLC, and the guidelines make clear recommendations for first, second, and third-line therapy for advanced disease.
Advanced disease.
Drug regimens that provide the greatest benefit and have acceptable toxicity for both physicians and patients should be the starting treatment regimen for patients with advanced lung cancer.
Staging, weight loss, status score, and gender can predict survival.
Platinum-based chemotherapy regimens can prolong survival, improve symptoms, and produce a better quality of life compared to supportive therapy.
The histology of NSCLC is important in the selection of systemic therapy.
The new drug/platinum combination for suitable patients can lead to a stable level of the following indicators: overall remission rate of about 25-35%, time to disease progression of 4-6 months, median survival of 8-10 months, 1-year survival of 30%-40%, and 2-year survival of 10%-15%.
Patients of any age with poor physical status (score 3-4) do not benefit from cytotoxic therapy unless they are EGFR mutation-positive patients treated with erlotinib.
First-line treatment
Bevacizumab + chemotherapy or chemotherapy alone can be used in patients with advanced or recurrent NSCLC with PS 0-1. Bevacizumab needs to be used until disease progression.
Cetuximab + vincristine/cisplatin is an option for patients with status score 0-1 (Level of Evidence 2B).
Erlotinib is recommended as first-line therapy for patients with EGFR mutations and should not be used as first-line therapy for patients with negative EGFR mutations or unknown mutation status.
Afatinib can be used in patients with EGFR mutations.
Crizotinib can be used in patients with ALK rearrangements.
For patients with non-squamous cancers, cisplatin/pemetrexed offers better efficacy and reduced toxicity than cisplatin/gicitabine.
For patients with squamous carcinoma, cisplatin/gicitabine provides better efficacy than cisplatin/pemetrexed.
A two-drug regimen is preferred, with a third cytotoxic agent increasing remission rates but not benefiting survival.
Monotherapy or platinum-based combination regimens are reasonable options for PS 2 or elderly patients.
Combinations of cisplatin or carboplatin with: paclitaxel, docetaxel, gemcitabine, etoposide, vincristine, vincristine, pemetrexed, and albumin-bound paclitaxel are effective.
New drug/non-platinum combinations are a reasonable choice when there are data showing tolerable activity and toxicity (e.g., gemcitabine/docetaxel, gemcitabine/vincristine).
Maintenance therapy
Continued maintenance therapy refers to the continuation of at least one of these agents after 4-6 cycles of first-line therapy with no disease progression. Switching maintenance therapy means starting a different drug than the first-line regimen after 4-6 cycles of first-line therapy with no disease progression.
Continued maintenance: Bevacizumab and cetuximab in combination with chemotherapy should be continued until disease progression or unacceptable toxicity occurs, as numerous clinical trials support this use.
Continuation of bevacizumab therapy after 4-6 cycles of platinum-based two-drug chemotherapy and bevacizumab therapy (Level of Evidence 1)
Continuation of cetuximab therapy after 4-6 cycles of cisplatin, vincristine, and cetuximab (Level of Evidence 1)
Continuation of pemetrexed therapy after 4-6 cycles of cisplatin and pemetrexed chemotherapy for patients with a histologic type other than squamous cell carcinoma (Level of Evidence 1)
Continuation of bevacizumab + pemetrexed therapy after 4-6 cycles of bevacizumab, pemetrexed, and cisplatin/carboplatin for patients with histologic types other than squamous cell carcinoma
Continuation of gemcitabine therapy after 4-6 cycles of platinum-based two-drug chemotherapy (Level of Evidence 2B)
Switching to maintenance: Two studies showed a progression-free survival and overall survival benefit from starting pemetrexed or erlotinib therapy in patients with progression-free disease after first-line chemotherapy.
Initiation of pemetrexed therapy after 4-6 cycles of first-line platinum-based two-drug chemotherapy for patients with histologic types other than squamous cell carcinoma (Level of Evidence 2B)
Initiation of erlotinib therapy after 4-6 cycles of first-line platinum-based two-drug chemotherapy (Level of Evidence 2B)
Start docetaxel therapy after 4-6 cycles of first-line platinum-based two-drug chemotherapy for patients with squamous cell carcinoma (Level of Evidence 2B)
Second-line therapy
For patients with disease progression during or after first-line therapy, single-agent docetaxel, pemetrexed, or erlotinib are all available as second-line agents.
Docetaxel is superior to vincristine or isocyclophosphamide
In patients with adenocarcinoma and large cell carcinoma, pemetrexed is considered comparable to docetaxel with less toxicity
Erlotinib is superior to best supportive care
Afatinib is available for patients with EGFR mutations
Ceritinib is available for patients with ALK rearrangement who have disease progression with crizotinib or are intolerant to crizotinib
Third-line therapy
Options for PS 0-2 patients include docetaxel, pemetrexed (non-squamous), erlotinib, or gemcitabine (Level of Evidence 2B), if not already in use
Note: If not otherwise noted, the recommendation level is 2A.