Best Practices in Treatment Selection for Patients with Advanced NSCLC

Abstract

Worldwide, lung cancer is the most prevalent form of cancer, and its non-small-cell subtype constitutes up to 85% of cases. Overall, lung cancer is the most common cause of cancer-related death in the United States for both sexes, and its 5-year survival rate is 17%. It is a heterogeneous disease characterized by a variety of biomarkers and differing histologies. Non-small-cell lung cancer may be squamous or nonsquamous in nature and fueled by a number of oncodrivers. Obtaining sufficient tissue during biopsy to perform thorough biomarker testing is a challenge but essential for the modern, targeted therapeutic environment. Although platinum-based doublets still play a major role in first-line treatment, novel therapeutic agent targeting BRAF, EGFR, ALK, and ROS1, as well as agents targeting the T790M mutation, may offer options for patients whose disease fails to respond to initial therapy or relapses following an initial response. The emergence of immunotherapy as second-line standard therapy has changed the treatment paradigm. Some patients will have more favorable outcomes in the first-line setting with immunotherapy. However, managing lung cancer has become more complex than it was 15 years ago when the challenge of treatment was seen as being only binary, ie, small-cell vs non-small-cell disease.

An Update on Predictive Biomarkers for Treatment Selection in Non-Small Cell Lung Cancer

“…Nonsquamous histology has been shown to be a predictive factor in the use of pemetrexed chemotherapy [ 12 ]. Several clinical trials have demonstrated that pemetrexed, when given as a single agent or combined with a platinum analog, provided survival benefit in patients with nonsquamous NSCLC, but showed only some activity in squamous cell patients [ 7 , 13 , 14 ]. For advanced stage squamous cell NSCLC patients, platinum combined with paclitaxel, docetaxel, gemcitabine or vinorelbine are currently the standard treatment options [ 15 ].…”

“…Several candidate predictive biomarkers may also potentially be useful to identify patients for emerging targeted therapy approaches. These include RET rearrangements and MET alterations [ 14 , 16 , 20 ]. MET is considered a strong candidate given its response to crizotinib, currently a treatment for ALK - and ROS1 -rearranged lung cancers [ 14 , 25 ], however, MET alterations are uncommon, occurring in approximately 5% of NSCLC.…”

Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway

“…In 2015, an estimated 73,330 new lung cancer cases and 61,020 new lung cancer mortalities were reported in China [ 2 ]. Lung cancer is divided into two major histological types: SCLC (small-cell lung cancer) and NSCLC, with the latter accounting for 85% of all lung cancers [ 3 ]. NSCLC includes adenocarcinoma, squamous cell carcinoma, and large cell lung cancer.…”

Therapeutic cancer vaccine: phase I clinical tolerance study of Hu-rhEGF-rP64k/Mont in patients with newly diagnosed advanced non-small cell lung cancer

“…Second-line chemotherapy may include pemetrexed in non-squamous cancer and docetaxel or erlotinib (or both) in all types of NSCLC. NSCLC management has positively evolved from the emergence of immunotherapy, currently positioned as second line therapy [ 18 ]. Antitumor activity, long lasting response and survival increases in advanced NSCLC patients has been demonstrated with the use of anti-PD-1 passive immunotherapy [ 19 ], leading to regulatory approval of an anti-PD-1 drug, nivolumab (Opdivo; Bristol-Myers Squibb) [ 20 ] for the treatment of metastatic squamous non–small-cell lung cancer (NSCLC) in patients who have progressed on a platinum-based chemotherapy.…”