TREATMENT OVERVIEW
Lung cancer treatments are based on various factors, including tumor operability, the patient’s performance status, and the stage of the disease, which is determined by primary tumor size (T), regional lymph node involvement (N), and presence of distant metastasis (M).1,7
Operable tumors, which are generally T1-2 (less than 7 cm) and have no lymph node involvement, are initially treated with a lobectomy and mediastinal lymph node dissection, followed by adjuvant chemotherapy, radiation, or both. These patients can also receive neoadjuvant chemotherapy or chemoradiotherapy preoperatively to increase the chances of achieving a complete response. Depending on the extent of the disease, adjuvant treatment involves chemotherapy with or without radiotherapy (RT). Most first-line chemotherapy regimens are platin-based combination therapies because they have been shown to prolong survival and improve quality of life. Patients with progressive disease or poor performance status primarily receive palliative symptom management.1,7
Continue Reading
Non-small cell lung cancer (NSCLC) Resectable tumors with limited lymph node involvement are generally treated with surgery and neoadjuvant, adjuvant chemotherapy with or without RT. More invasive tumors, including those with more lymph node involvement, require chemoradiation treatments.1
Treatment for NSCLC depends on the histology of the tumor, especially in metastatic (advanced) disease. Adenocarcinomas, large cell carcinomas, and NSCLCs not otherwise specified should be tested for EGFR mutations and presence of anaplastic lymphoma kinase (ALK) receptors. Squamous cell carcinomas, however, are only tested in specific populations. Certain medications are added to treatment regimens if the patient is EGFR mutation positive (eg, erlotinib [Tarceva] and afatinib [Gilotrif]) or ALK positive (eg, crizotinib [Xalkori])1 (Table 1).
Table 1. NCCN recommended NSCLC treatments1
| Treatment | Chemotherapy options |
| Neoadjuvant/adjuvant | • Carboplatin + paclitaxel • Cisplatin + either vinorelbine, etoposide, vinblastine, gemcitabine, docetaxel, or pemetrexed |
| Concurrent chemotherapy and RT | Cisplatin + either etoposide or vinblastine |
| Sequential chemotherapy and RT | • Carboplatin + paclitaxel • Cisplatin + vinblastine |
| Systemic therapy for advanced disease: First line | • Afatiniba • Bevacizumab + carboplatin + paclitaxel • Carboplatin + paclitaxel • Cetuximab + cisplatin + vinorelbine • Cisplatin + either gemcitabine, docetaxel, vinorelbine, or pemetrexed • Crizotinib • Erlotinibb |
| Systemic therapy for advanced disease: Second line | • Docetaxel • Erlotinib • Pemetrexed |
| Systemic therapy for advanced disease: Third line | Erlotinibb |
| aAfatinib was approved after the 2013 NCCN guidelines update, and so is not currently included in the guidelines. bThis is a new FDA -approved indication for erlotinib. Key: NCCN , National Comprehensive Cancer Network; NSCLC , non-small cell lung cancer; RT , radiotherapy. |
|
Updates in treating NSCLC Among the numerous treatment updates in 2013, two new medications recently received FDA approval. Afatinib was approved as a first-line treatment option for metastatic NSCLC in July.9 Erlotinib was also approved for the first-line treatment of metastatic NSCLC in May; this is in addition to its previous indications, which were only for the maintenance and second/third-line treatment of NSCLC, as well as first-line treatment of pancreatic cancer. Erlotinib is not recommended for use in combination with platinum-based chemotherapy.8
Erlotinib reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signaling. Erlotinib’s binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations is higher than its affinity for the wild-type receptors that appear on normal cells.8
Unlike erlotinib, afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4), and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling. Afatinib inhibits autophosphorylation and in vitro proliferation of cell lines expressing wild-type EGFR, or those expressing selected EGFR exon 19 deletion mutations or exon 21 (L858R) mutations. Afatinib also inhibits in vitro proliferation of cell lines overexpressing HER2.9
Erlotinib’s and afatinib’s mechanism of actions can be quantified by each of their clinical efficacy trials. In a randomized, open-label clinical trial conducted in Europe, researchers concluded the median progression free survival (PFS) for erlotinib-treated patients was 9.7 months (n=86; 95% confidence interval [CI] 8.7-12.9; P<.0001) compared with 5.2 months for chemotherapy-treated patients (n=88; 95% CI 4.6-6; P<.0001).10 Table 2 is a summary of the observed adverse events.
Table 2. Observed adverse effects experienced by patients taking erlotinib (Tarceva)8
| Adverse effect | Percent of patients (N=84) |
| Back pain | 19% |
| Conjunctivitis | 18% |
| Cough | 48% |
| Diarrhea | 62% |
| Dry Skin | 21% |
| Dyspnea | 45% |
| Paronychia | 14% |
| Pruritus | 16% |
| Rash | 85% |
| Rhinorrhea | 18% |
Afatinib also demonstrated positive results in a clinical trial. In a randomized, multicenter, open label trial, the researchers found the median PFS was 11.1 months (n=230; 95% CI 9.6-13.6; P=.001) for afatinib-treated patients, compared with 6.9 months for patients undergoing treatment with pemetrexed/cisplatin (n=115; 95% CI 5.4-8.2; P=.001).11 Table 3 is a summary of the observed adverse events.
Table 3. Observed adverse effects experienced by patients taking afatinib (Gilotrif)9
| Adverse effect | Percent of patients (N=229) |
| Conjunctivitis | 11% |
| Decreased Appetite | 29% |
| Diarrhea | 96% |
| Dry Skin | 31% |
| Epistaxis | 17% |
| Paronychia | 58% |
| Pruritus | 21% |
| Rash | 90% |
| Rhinorrhea | 11% |
| Stomatitis | 71% |
