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Drug therapy for non-small cell lung cancer

General

Chemotherapy for non-small cell lung cancer is used as adjuvant treatment after curative surgery and in combination with radical radiation therapy. It will also often be relevant in palliative situations.

Adjuvant chemotherapy

Adjuvant chemotherapy has been shown to increase survival after surgery for patients with stage II and stage III cancer, but this effect is not seen for patients in stage IA. Benefit may be seen in stage IB cancers more than 4 cms in maximal dimension. Five year survival increases by 5-15% in absolute figures. Chemotherapy can be given in combination with curative radiation therapy (concomitantly). Neoadjuvant chemotherapy is usually not given for non-small cell lung cancer, except in some cases of Pancoast syndrome (apical lung tumors invading the thoracic wall).

Palliative chemotherapy

At the time of diagnosis, 70% of patients with non-small lung cancer are in a palliative stage. In patients of this group, platinum-based chemotherapy may relieve symptoms or delay the appearance of such, and thereby improve quality of life. Furthermore, palliative chemotherapy prolongs survival for some months. A prerequisite is that the patient is in good general health, i.e. performance status (PS) 0-2. Response to palliative conventional chemotherapy is expected in about 3 of 10 patients in first-line situations and in 1 of 10 by second-line treatment. At present it is not possible to predict whether a patient will benefit from chemotherapy.

Patients with activating mutations in the gene that codes for epidermal growth factor receptor (EGFR), about 10% of all, should be offered peroral treatment with tyrosin kinase inhibitors, such as erlotinib, gefitinibor or afatinib. Such therapy has shown significantly better efficacy than conventional chemotherapy. The response rate are approximately 70% in patients positive for this mutation. Time to disease progression is on average about one year.

About 5% of the patients with non-small cell lung cancer have changes in the ALK gene.
The ALK inhibitors have shown effectiveness in these patients similar to patients treated with EGFR inhibitors mentioned above. Crizotinib is an oral ALK inhibitor and approved as second line treatment in ALK-positive patients.

EGFR-mutation status should also be analyzed in conjunction with histopathological diagnostics whenever a NSCLC of non-squamous cell carcinoma subtype.

Predictive factors

The most important predictive factor for chemotherapy effect, except for the TNM stage, is performance status. The risk of serious side effects increases in patients with a performance status of 3 or 4. In these cases, chemotherapy is not recommended. Norwegian data indicates that performance status 2 has the greatest benefit from treatment in terms of improved quality of life, since symptom relief exceeds side effects to a greater degree than in those with better general health condition. Tyrosin protein kinase inhibitors have a different side effect-profile than conventional chemotherapeutics, and can be tried out in mutation-positive patients with performance status 3.

Chemotherapy in elderly patients with non-small cell lung cancer

Over half of patients with non-small cell lung cancer are older than 65. However, elderly patients are underrepresented in clinical studies and the evidence for chemotherapy in this group is therefore limited. Functional level, comorbidity with polypharmacy, socioeconomic and cognitive factors, as well as nutritional status, can vary significantly among this heterogeneous patient group. The decision to administer chemotherapy should be based on a total geriatric assessment of these factors. Patients in good general health status (PS 0-2) with normal organ function may benefit from platinum-based doublet chemotherapy. Elderly patients of a reduced general health condition are offered monotherapy with a newer drug such as vinorelbine, gemcitabine, pemetrexed (only non-squamous carcinoma), docetaxel or, in mutation-positive patients, tyrosine kinase inhibitors.

Indications

  • Postoperative chemotherapy – patients in stage II and III who have been operated. 
  • Chemotherapy in combination with curative radiation treatment - patients in stages IIIa and IIIb who can receive curative radiation treatment.
  • Palliative chemotherapy – patients with stage IV.

Goal

  • For postoperative chemotherapy and chemotherapy given in combination with curative radiation therapy, the goal is to increase the probability of curing the disease.  
  • Relieve symptoms and ailment, and prolong life, in palliative treatment.

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