IASLC Thoracic Oncology E-Book

Harvey Pass, David Ball, Giorgio Scagliotti

• Publisher: Elsevier
• Year: 2017
• ISBN:
  9780323527842
• Edition: 2
• Topic: Medizin
• Subtopic: Onkologie

Global experts, in conjunction with the International Association for the Study of Lung Cancer, bring you up to date with today's best approaches to lung cancer diagnosis, treatment, and follow-up. IASLC Thoracic Oncology, 2nd Edition, keeps you abreast of the entire scope of this fast-changing field, from epidemiology to diagnosis to treatment to advocacy. Written in a straightforward, practical style for the busy clinician, this comprehensive, multidisciplinary title is a must-have for anyone involved in the care of patients with lung cancer and other thoracic malignancies.

• Offers practical, relevant coverage of basic science, epidemiology, pulmonology, medical and radiation oncology, surgery, pathology, palliative care, nursing, and advocacy.
• Provides authoritative guidance from the IASLC – the only global organization dedicated to the study of lung cancer.

• Includes new content on molecular testing, immunotherapy, early detection, staging and the IASLC staging system, surgical resection for stage I and stage II lung cancer, and stem cells in lung cancer.
• Features a new full-color design throughout, as well as updated diagnostic algorithms.

Section IX

Chemotherapy and Targeted Agents for Lung Cancer

Outline

44. Frontline Systemic Therapy Options in Nonsmall Cell Lung Cancer

45. Systemic Options for Second-Line Therapy and Beyond

46. Maintenance Chemotherapy for Nonsmall Cell Lung Cancer

47. Pharmacogenomics in Lung Cancer: Predictive Biomarkers for Chemotherapy

48. New Targets for Therapy in Lung Cancer

49. Management of Toxicities of Targeted Therapies

50. Immunotherapy and Lung Cancer

51. Adjuvant and Neoadjuvant Chemotherapy for Early-Stage Nonsmall Cell Lung Cancer

52. Treatment of Extensive-Stage Small Cell Lung Cancer

44

Frontline Systemic Therapy Options in Nonsmall Cell Lung Cancer

Suresh S. Ramalingam, Rathi N. Pillai, Niels Reinmuth, and Martin Reck

Keywords

ALK; biomarkers; chemotherapy; cisplatin; EGFR; immune checkpoint inhibition; PD-1; pemetrexed

Summary of Key Points

• The determination of tumor histology in nonsmall cell lung cancer (NSCLC) has become essential in treatment decision-making due to differential efficacy and toxicities seen with newer therapies.

• International Association for the Study of Lung Cancer (IASLC) guidelines recommend testing all patients with lung adenocarcinoma for both EGFR mutations and ALK rearrangements.

• Further molecular profiling of both adenocarcinoma and squamous cell lung cancers has identified novel driver mutations that are being investigated as potential targets of new therapies.

• Platinum doublet chemotherapy is the established standard first-line therapy in patients with advanced or metastatic NSCLC.

• The duration of platinum-based first-line therapy should be four to six cycles.

• Triple drug chemotherapy in NSCLC does not improve survival and often results in increased toxicity.

• ERCC1 and RRM1 have not been useful as predictive biomarkers for selection of chemotherapy based on prospective randomized clinical trials.

• Bevacizumab has been approved in combination with chemotherapy for the first-line therapy of patients with advanced NSCLC with nonsquamous histologies. Other antiangiogenic therapies in NSCLC have been disappointing.

• Patients with activating mutations in EGFR benefit from upfront therapy with EGFR tyrosine kinase inhibitors.

• Patients with ALK rearrangements can be successfully treated with ALK inhibitors, such as crizotinib.

• For patients with tumor PDL-1 expression >50%, pembrolizumab, an immune checkpoint inhibitor, is superior to platinum-based chemotherapy.

• Elderly patients with advanced NSCLC benefit from combination chemotherapy; selection of appropriate patients is vital.

• Patients with borderline performance status can also benefit from combination chemotherapy; patient selection requires careful consideration of comorbidities.

Lung cancer presents at an advanced stage at the time of diagnosis in the majority of patients. The overall goals of treatment for advanced stage disease are palliation and improvement in survival. Local treatment modalities such as radiotherapy and surgery play a limited role and are implemented primarily for symptom control. Systemic therapy remains the principal therapeutic modality for advanced stage nonsmall cell lung cancer (NSCLC). Until the late 1990s, treatment of advanced lung cancer followed the straightforward algorithm of platinum-based combination therapy, irrespective of histologic subtype, without any option for further lines of treatment. With the introduction of so-called third-generation cytotoxic drugs, the treatment of NSCLC changed and overall survival improved to approximately 8 months for patients with a good performance status. In the past two decades, there has been a gradual shift in therapy from the use of systemic chemotherapy in all patients, to the current approach in which histology and molecular status play a key role in treatment selection (Fig. 44.1). This has been made possible by greater insights into lung cancer biology, the availability of novel therapeutic agents, and the increasing focus on identification of biomarkers to guide therapy.¹ As a result, while a cure from advanced NSCLC still remains elusive, a significant subset of patients has long-term survival and an improved quality of life.

Prognostic Factors in Nonsmall Cell Lung Cancer

The assessment of prognosis is an important factor affecting the selection of appropriate treatment for each individual patient. The variables that are associated with prognosis can be grouped into categories: tumor-related, such as primary site, histology, and extent of disease; patient-related, such as performance status, comorbidity, and sex; and environmental factors, such as nutrition and the choice and quality of treatment.

Clinical Factors

Performance status and comorbid conditions are amongst the most important prognostic factors. Moreover, these determinants are also of utmost importance for the selection of therapy, as outlined later. The systematic determination of comorbidities is an essential component to preselect appropriate chemotherapy regimens and to provide the best supportive care.

In addition to noncancer-related comorbidities, patients also suffer from symptoms related to the primary tumor, mediastinal spread, or paraneoplastic syndromes. Moreover, lung cancer commonly produces systemic effects such as anorexia, weight loss, weakness, and profound fatigue. In a study of 12,428 NSCLC patients in the international staging database of the International Association for the Study of Lung Cancer (IASLC), performance status, age, and gender appeared to be independent prognostic factors for survival in addition to clinical stage.² In advanced NSCLC, some routine laboratory tests (mainly white blood cells and hypercalcemia) were also found to be significant prognostic variables. Nowadays, the clear majority of lung cancer cases are diagnosed in patients aged >65 years.³ Age at diagnosis is another important factor that needs to be considered for therapy decision making. Often, increasing age is accompanied by multiple comorbidities, which further limit therapeutic options and outcome of the patient.

Fig. 44.1 Treatment algorithm for treatment-naive NSCLC. ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; IASLC, International Association for the Study of Lung Cancer; NSCLC, nonsmall cell lung cancer.

Ethnicity

While lung cancer remains a leading cause of mortality for all races, recent research has focused on ethnic variations in this disease. One of the most striking disparities seen is the difference in lung cancer risk and survival for African and Asian ethnicities. For example, the epidermal growth factor receptor (EGFR) mutation rate differs considerably between various ethnicities. Epidemiologic research has focused on behavioral, cultural, and socioeconomic factors that may influence risk, although no clear link has been established.⁴ Access to care is also variable among various ethnic groups and remains an important barrier to the delivery of optimal therapy.

Tumor Stage

The anatomic extent of the disease, as described by the TNM classification, is the most important prognostic factor in NSCLC. The seventh edition of the TNM classification that came into effect in 2010 derived from the analysis of the largest database ever generated for this purpose, with data from 46 sources in more than 19 countries around the world and with information about patients treated with all modalities of care.^5,6 An important change involved the recognition that patients with extrathoracic disease have a slightly less favorable outcome compared with patients with metastatic spread confined to the thorax, even within the stage IV category. This has resulted in the division of stage IV to M1a and M1b based on the presence or absence of extrathor...