Immunotherapy in older patients with non-small cell lung cancer: Young International Society of Geriatric Oncology position paper.

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population.

Making Checkpoint Inhibitors Part of Treatment of Patients With Locally Advanced Lung Cancers: The Time Is Now.

The PACIFIC trial of durvalumab administered for 1 year to patients with stage III lung cancers has set a new standard of care. PACIFIC established the role of immune checkpoint inhibitors (ICIs) for individuals with inoperable and unresectable locally advanced lung cancers that achieve disease control from concurrent chemoradiation. For patients with resectable and operable disease, ICIs administered before surgery, either alone (JHU/MSK, LCMC3, and NEOSTAR) or in combination with chemotherapy (Columbia/MGH and NADIM), have yielded high rates of major pathologic response in resection specimens, an outcome measure that correlates with improved progression-free survival and overall survival. These results have brought forth the dilemma of how to choose the optimal local therapy-either definitive concurrent chemoradiation or surgery-to use with an ICI for patients with stage III lung cancers that are both operable and resectable. Here, we review the data that support the use of each local therapy. Recent successes have also raised the possibility that using ICIs in patients with earlier stages of lung cancer will enhance curability. Randomized trials are underway; however, until they read out, physicians must choose between local and systemic therapies on the basis of the information we have today. Research demonstrates that using surgery, radiation, chemotherapy, and ICIs improve all efficacy outcomes and curability. All modalities should be considered in every patient with locally advanced lung cancer. It is imperative that a multimodality discussion that includes the possible addition of ICIs takes place to choose the best modality and sequence of therapies for each patient.

Safety of pembrolizumab for the treatment of melanoma.

INTRODUCTION: The immune checkpoint inhibitor pembrolizumab is the first anti-programmed-death-1 (PD-1) drug licensed by the FDA. It has been approved for the treatment of advanced melanoma, thanks to its positive results in terms of efficacy and its favorable toxicity profile. However, it is not exempt from side effects. In general, these are usually mild and easily manageable but there are pembrolizumab-induced immune-related adverse events (irAEs) that can be severe. Therefore, the understanding, diagnosis and management of those side effects are essential for the optimal care of patients treated with pembrolizumab. AREAS COVERED: In this article, the safety and efficacy of pembrolizumab in melanoma are extensively reviewed as well as its mechanism of action and the role of the PD-1 pathway in cancer. Also, its profile of side effects is compared with other immune checkpoint inhibitors such as ipilimumab and nivolumab. EXPERT OPINION: Pembrolizumab is generally a well-tolerated drug but irAEs are not infrequent. However, these are usually mild and easily manageable in most cases. Early diagnosis and correct management of side effects induced by immune checkpoint inhibitors such as pembrolizumab should be areas of further work in forthcoming years.