Evolving Standards of Care in Melanoma and Non-Small Cell Lung Cancer

Source: Targeted Oncology , April 2019

The emerging role of immunotherapy in melanoma and non–small cell lung cancer (NSCLC) has had a transformative effect on how these 2 cancer types have been managed over the past few years. A new paradigm has evolved where immunotherapy is now not only a new modality but is the dominant therapeutic approach in this disease in progressively earlier lines of therapy, including unresectable, resectable, and adjuvant therapy.

Melanoma

First, it should be recognized that for many patients up-front surgical therapy on the primary tumor with or without some nodal dissection, such as a sentinel lymph node biopsy, is standard of care. However, regional or distant relapse still may occur, and this has led to the institution of adjuvant therapies. In some situations, the unresectable disease status must be treated with systemic therapy to treat distant risk or distant clinically apparent disease. The history of innovative systemic therapies beyond chemotherapy for melanoma began with the interferon story in the 1990s. Historically, the use of interferon as an adjuvant was based on the fact that metastatic melanoma was and is a deadly disease, and early intervention could lead to improved long-term cure rates. Furthermore, the prognostic factors for assessing risk of recurrence have evolved but are now becoming more clearly defined. Interestingly, numerically, most deaths still originate in patients with intermediate (stage II/III) disease. Interferon alpha-2B was used in different dosages and frequencies in a series of clinical trials. However, controversy has surrounded the interferon story in the adjuvant setting for several reasons. First, only ECOG 1684 showed an overall survival (OS) advantage, whereas other trials showed only a recurrence-free survival (RFS) advantage.¹ In addition, which dosage and/or schedule to use was also unclear. This is more important in the setting of an agent like interferon, in which toxicity is significant, including potential constitutional symptoms, myelosuppression, hepatotoxicity, chronic fatigue, and other neurologic/psychologic effects. More recently, interferon has been superseded by newer agents.