Recent advances in clinical diagnosis and treatment of squamous lung cancer Ma Zhongxia, Chest Tumor Lung Cancer Treatment Center, South Hospital, Chenzhou First People’s Hospital
Composition ratio of squamous carcinoma
Adenocarcinoma accounts for 60% of all lung cancer types and is the most common; lung squamous carcinoma accounts for 20%; small cell lung cancer drops to 13%.
Pathological diagnosis
In addition to morphology, squamous carcinoma is characterized by positive immunohistochemical staining for P40 and P63, whereas adenocarcinoma is positive for NapsinA and TTF-1. The diagnosis of “non-specific” or large cell carcinoma is rarely made when the morphology is observed on the basis of HE-stained sections in combination with immunohistochemistry. Only a sufficient number of specimens are available to allow the pathologist to make a more accurate diagnosis and provide more comprehensive information.
Multiple molecular tests are available for squamous lung cancer
Current NCCN guidelines recommend multiple genetic tests for some squamous carcinomas: those who have never smoked or those whose specimens are too small to diagnose squamous carcinoma with confidence by morphology.
If KRAS mutations are detected in the specimen, squamous carcinoma can basically be ruled out and is most likely adenocarcinoma.
FTFR1, PI3K and PTEN are the most studied molecules, and some related drugs have been developed.
An article by Schildhaus published in Clinical Cancer Research in February this year found that 3% of squamous carcinomas have high levels of MET amplification, suggesting that crizotinib is sensitive and could potentially be a therapeutic agent for some patients with squamous lung cancer.
Two new drugs for squamous lung cancer
In the past few months, two drugs have been approved for squamous lung cancer. nivolumab (OPDIVO) was approved by the FDA for advanced or metastatic squamous lung cancer on March 4, 2015, three months earlier than expected. the FDA approval was based on a phase III clinical trial: CheckMate-017.
The CheckMate-017 trial
272 previously treated advanced or metastatic squamous lung cancers were randomized to either (1) the humanized IgG4 monoclonal antibody nivolumab 3 mg/kg IV every 2 weeks s (n = 135) arm, or (2) docetaxel 75 mg/m2 IV every 3 weeks (n = 137).
Survival in the nivolumab-treated group was prolonged by 3 months compared with the docetaxel control group (9.2 vs 6 months).
The NCCN released the 5th edition of its 2015 clinical practice guidelines for non-small cell lung cancer on March 9, and the highlight of the latest update is the addition of the PD-1 inhibitor nivolumab (Opdivo) as an option for progression after first-line therapy for advanced squamous cancer.
Another recent approval is for ramucirumab (ramucirumab), an antibody to the vascular endothelial growth factor receptor 2, in combination with docetaxel.
How to choose
Some experts prefer first-line options of cisplatin and gemcitabine. Of course, a paclitaxel-combined platinum regimen is also an option.
However, after progression on first-line chemotherapy, nivolnmab is recommended as the preferred choice because it beat docetaxel in the head-to-head study described above.
Some experts suggest that the order of treatment options for advanced squamous cancer should be: cisplatin in combination with gemcitabine in first line, nivolumab after progression, and docetaxel + ramolutumab in third place.
This leaves an open question: is docetaxel + ramolutumab better than nivolumab alone? Given that nivolumab benefits patients regardless of which line it is used in, it seems more reasonable to choose it as second line and to prepare docetaxel + ramolutumab as third line.
Summary
Overall, we have made many advances in squamous carcinoma, both in terms of collaborating with pathologists and molecular pathologists to better diagnose and molecularly characterize squamous carcinoma, and in terms of rationalizing the use of these two new drugs that have suddenly joined the “team” to develop a rational first-line and follow-up treatment plan for patients.