Adjuvant chemotherapy for early-stage non-small cell lung cancer: the past, the present and the future

Complete resection is mandatory in order to achieve a cure in patients with early-stage non-small cell lung cancer (NSCLC). However, despite complete resection, a substantial proportion of patients have disease recurrence, with distant metastases being the primary sites of failure. Recent trials have conclusively demonstrated the benefit of platinum-based adjuvant therapy in patients with resected stage IB and II NSCLC. The role of adjuvant chemotherapy in resected stage III NSCLC is less clear, with trials showing conflicting results. The role of targeted agents in this setting is being investigated. Gene expression profiling studies should help direct chemotherapy to those who would actually benefit from it, thereby saving others from unnecessary toxicity.     

Adjuvant chemotherapy for early-stage non-small cell lung cancer: the past,the present and the future

Complete resection is mandatory in order to achieve a cure in patients with early-stage non-small cell lung cancer (NSCLC). However, despite complete resection, a substantial proportion of patients have disease recurrence, with distant metastases being the primary sites of failure. Recent trials have conclusively demonstrated the benefit of platinum-based adjuvant therapy in patients with resected stage IB and II NSCLC. The role of adjuvant chemotherapy in resected stage III NSCLC is less clear, with trials showing conflicting results. The role of targeted agents in this setting is being investigated. Gene expression profiling studies should help direct chemotherapy to those who would actually benefit from it, thereby saving others from unnecessary toxicity.     

The 800-lb gorilla we all ignore: treatment of NSCLC in elderly and PS 2 patients

Patients with non-small cell lung cancer,NSCLC, typically have advanced disease on presentation. First-line palliative platinum-based doublet chemotherapy has emerged as the standard of care in fit, younger patients. However, patients with advanced age and/or impaired performance status have been relatively underrepresented in clinical trials. Retrospective analyses and the few existing prospective randomized trials in these populations have suggested a poorer overall prognosis, yet also provide evidence of benefit from systemic therapy. Toxicity is generally manageable, and in most cases, comparable to that of younger, healthier patients. There are clearly expanding roles for nonplatinum chemotherapy agents and newer targeted therapies, which have generally yielded decreased toxicity compared to platinum-based chemotherapy without sacrificing efficacy. Appropriate pretreatment assessment and proper patient selection is of paramount importance; it is imperative to treat patients who are most likely to garner benefit. In summary, data suggest that these relatively neglected populations of NSCLC patients can be safely treated, and can benefit from palliative systemic therapy. Single-agent chemotherapy is generally recommended over combination chemotherapy, although investigation of newer targeted therapies or alternative agents may allow for combination therapy in the near future. Further prospective investigation is absolutely warranted.     

Pembrolizumab for the first-line treatment of non-small cell lung cancer

Introduction: Platinum-based chemotherapy had long played a role as standard therapy for the first-line treatment of advanced or recurrent non-small cell lung cancer (NSCLC). However, immune checkpoint inhibitors such as pembrolizumab, a monoclonal antibody that prevents programmed death protein 1 (PD-1) receptor, have brought a paradigm shift in this field.

Areas covered: In this article, we review the relevant literatures and ongoing trials on the first-line treatment of pembrolizumab. Especially, in two pivotal phase III trials, KEYNOTE-024 and ?189, both pembrolizumab monotherapy and combined pembrolizumab plus chemotherapy significantly prolonged overall survival (OS) compared to the existing platinum-based chemotherapy. Currently, multiple trials with combination therapy of pembrolizumab and other agents have been conducted, and further evidences are expected to be created.

Expert opinion: Immune checkpoint inhibitors that block the PD-1/PD-L1 pathway are essential drugs for advanced or recurrent NSCLC, among which pembrolizumab becomes one of the standards of care in the first-line of NSCLC. For further improvement in efficacy of pembrolizumab, it is necessary to clarify the identification of biomarkers exclusive to PD-L1 expression, predictive factors for patients who benefit most from the agent.     

Duration of therapy in advanced, metastatic non-small-cell lung cancer

Advanced, metastatic non-small-cell lung cancer (NSCLC) remains a challenge to oncologists. There is little doubt that platinum-based combination chemotherapy improves survival and has a palliative effect by improved patients' symptoms and quality of life. Yet chemotherapy is not curative, is associated with toxicity, and can be costly. In most recent phase III trials, the median survival time is 8 to 10 months. Therefore, the optimal duration of therapy-one that balances survival and palliative effects against toxicity, cost, and intrusiveness on patients' lives-remains an important issue. Three recent randomized trials that addressed this in stage IIIB/IV NSCLC are reviewed. Two evaluated brief durations of first-line therapy (3 cycles in one, 4 in the other) versus longer-duration therapy (6 cycles and continuous therapy, respectively). No benefit in response rate, symptom relief, quality of life, or survival was noted for the longer-duration therapy. In addition, cumulative toxicities occurred more frequently in patients who received longer treatment durations. The third trial administered 4 cycles of first-line platinum-based therapy and then randomized responding patients to observation or 6 months of further therapy with vinorelbine. No survival benefit was noted for vinorelbine. There trials suggest that duration of first-line therapy in advanced, metastatic NSCLC should be brief (3 to 4 cycles). Prolonged therapy does not appear to improve survival and carries the risk of cumulative toxicity. Second-line therapy considered in those patients fit enough to receive it at the time of disease progression.     

Management of the elderly patient with advanced non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the most lethal of the common solid malignancies. It is predominantly a disease of the elderly with the median age at diagnosis 68 years. Unfortunately, the majority of patients present with advanced disease whereby palliation is the primary aim of treatment. The elderly have a long history of undertreatment and non-inclusion in clinical trials with regard to cancer. Elderly-specific studies demonstrate that chemotherapy provides both a survival and quality-of-life benefit in advanced NSCLC. Increasing emphasis is placed on the objective assessment of fitness for chemotherapy and the integration of molecularly targeted agents into treatment paradigms.     

The role of epidermal growth factor receptor in advanced non-small cell lung carcinoma

Chemotherapy is the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Over the past 20 years, advances in chemotherapy have shown minimal incremental improvement in the survival outcomes of patients with advanced NSCLC. With the identification of molecular and genetic alterations in lung cancer, several new potential rationally designed therapeutic targets have emerged. One of these is the epidermal growth factor receptor (EGFR) and member of the ErbB family of receptor tyrosine kinases. Several inhibitors, both antibodies directed at the extra-cellular portion of the receptor, and small molecule inhibitors directed at the tyrosine kinase domain of EGFR are in clinical development in lung cancer. This article will review the pre-clinical rationale and the clinical studies of EGFR inhibitors alone and/or in combination with chemotherapy that have been performed to date in advanced NSCLC.     

The role of epidermal growth factor receptor in advanced non‐small cell lung carcinoma

Chemotherapy is the standard of care for patients with advanced non‐small cell lung cancer (NSCLC). Over the past 20 years, advances in chemotherapy have shown minimal incremental improvement in the survival outcomes of patients with advanced NSCLC. With the identification of molecular and genetic alterations in lung cancer, several new potential rationally designed therapeutic targets have emerged. One of these is the epidermal growth factor receptor (EGFR) and member of the ErbB family of receptor tyrosine kinases. Several inhibitors, both antibodies directed at the extra‐cellular portion of the receptor, and small molecule inhibitors directed at the tyrosine kinase domain of EGFR are in clinical development in lung cancer. This article will review the pre‐clinical rationale and the clinical studies of EGFR inhibitors alone and/or in combination with chemotherapy that have been performed to date in advanced NSCLC.     

Molecular targeted therapy in lung cancer

Lung cancer continues to be the leading cause of cancer death worldwide, and nonsmall cell lung cancer(NSCLC) is the most common type of lung cancer. Despite many clinical trials of platinum-based chemotherapy in combination with various drugs, the median survival time of NSCLC patients remains poor. The overall 5-year survival rate is approximately 15%, and has improved only marginally over the last few decades despite the introduction of new therapeutic agents. A recent milestone in this field has been the development of molecular-targeting drugs, among which gefitinib and erlotinib targeting the epidermal growth factor receptor (EGFR) have improved the efficacy of therapy for NSCLC. Anti-angiogenetic drug, such as bevacizumab, had become clinical use in the treatment for NSCLC. Moreover, discovery of EML4-ALK made the marvelous progress in cancer research in NSCLC. In this review, we discuss about the development of molecular-targeting drugs, such as EGFR-TKI, anti-angiogenetic drug, and EMLA-ALK inhibitors.     

Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cancer

BACKGROUND: Erlotinib is an oral tyrosine kinase inhibitor, targeting the human epidermal receptor type 1/ epidermal growth factor receptor, recently approved by the US Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) after the failure of more than 1 or 2 previous chemotherapeutic regimens. OBJECTIVE: The purpose of this article is to summarize the development, pharmacology, pharmacokinetics, efficacy, and adverse effects of erlotinib. METHODS: A literature search was conducted with the MEDLINE and EMBASE (1999-2005) databases using the search terms non-small-cell lung cancer, erlotinib, and epidermal growth factor receptor inhibitor. Abstracts from the American Society of Clinical Oncology and documents submitted to the FDA also were reviewed. RESULTS: BR.21, a randomized, placebo-controlled, multinational Phase III trial demonstrated clinically and statistically improved overall survival in patients with advanced or metastatic NSCLC treated with erlotinib versus placebo as second-line therapy. The erlotinib group had a median survival of 6.7 months versus a median survival of 4.7 months in the placebo group (P < 0.001). The toxicity profile of erlotinib was moderately benign, with the most commonly documented adverse events requiring dose reductions including skin rash (12%) and diarrhea (5%). Interstitial lung disease and relative fatalities were reported infrequently (0.8%) in patients receiving erlotinib. Two randomized, placebo-controlled, multicenter Phase III trials conducted in patients with locally advanced and metastatic NSCLC showed no clinical benefit with first-line administration of erlotinib plus concurrent platinum-based chemotherapy. CONCLUSIONS: For patients with NSCLC in whom more than 1 or 2 previous chemotherapeutic regimens have failed, erlotinib is an effective therapy with significant overall survival benefits. The use of erlotinib as first-line therapy in combination with platinum-based chemotherapeutic regimens, however, has failed to demonstrate efficacy in the treatment of NSCLC.     

Ramucirumab for the treatment of advanced or metastatic non-small cell lung cancer

ABSTRACT

Introduction: On 12 December 2014, the U.S. Food and Drug Administration (FDA) approved ramucirumab for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy.

Areas covered: This review discusses the best treatment strategy for ramucirumab, a vascular endothelial growth factor receptor-2 inhibitor for patients with advanced NSCLC.

Expert opinion: The addition of ramucirumab to docetaxel in the treatment of patients with metastatic NSCLC who have progressed on or after platinum-based chemotherapy confers a 1.4-month improvement in overall survival, with an acceptable toxicity profile. The potential impact of the approval of the programmed death receptor-1 (PD-1)-blocking antibody nivolumab or pembrolizumab on the use of ramucirumab plus docetaxel in advanced NSCLC patient population is uncertain in clinical practice. In order to improve overall outcomes for patients with advanced NSCLC, both ramucirumab plus docetaxel and the PD-1-blocking antibody should be used in any treatment line.     

Advances in chemotherapy for non-small cell lung cancer

OBJECTIVES: To discuss the use of chemotherapy and targeted therapy for treating non-small cell lung cancer (NSCLC). DATA SOURCES: Published articles, book chapters, and research papers. CONCLUSION: Chemotherapy has improved both response and survival rates incrementally in patients with advanced NSCLC. Targeted therapy agents are now included in the treatment schema and are impacting overall survival in combination with chemotherapy for first-line therapy and as monotherapy for second- or third-line treatment. In recent years, chemotherapy has also shown efficacy in earlier stages of treatment, especially as adjuvant therapy after surgery. Additionally, elderly patients can tolerate platinum-based chemotherapy without significant toxicities; therefore, age should not be the only determining factor when deciding on treatment for an older person. IMPLICATION FOR NURSING PRACTICE: It is important for nurses to know and understand the background and rationale for many of the current treatments for NSCLC given today.     

恩度联合DP化疗方案治疗晚期非小细胞肺癌的临床研究

目的探讨恩度联合DP化疗方案(多西紫杉醇+顺铂)治疗晚期非小细胞肺癌患者的近期临床疗效,评价其临床应用的安全性和耐受性。方法 45例晚期非小细胞肺癌患者给予DP方案化疗同时联合恩度7.5 mg/m2,连用2周后暂停1周为1周期,至少完成2周期,观察近期疗效、疾病进展时间及不良反应。结果 45例患者中部分缓解18例(40.0%),稳定17例(37.8%),进展10例(22.2%),有效率为40.0%,临床受益率为77.8%。不良反应主要为骨髓抑制和胃肠反应,患者经对症处理后可以耐受。结论恩度联合含铂类DP化疗方案一线治疗晚期非小细胞肺癌是一种安全有效的方案。     

Robotic radical hysterectomy after neoadjuvant chemotherapy in locally advanced cervical cancer

Neoadjuvant platinum-based chemotherapy (NACT) plus radical hysterectomy and pelvic lymphadenectomy has been demonstrated to be a valid alternative to chemoradiation in patients with advanced cervical cancer. Several publications have reported on the feasibility of robot-assisted laparoscopy in early cervical cancer. Herein is reported the case of a woman with locally advanced cervical cancer that was successfully treated using neoadjuvant chemotherapy followed by total robotic type C1 radical hysterectomy (TRRH) plus pelvic lymphadenectomy. The success of this approach, which is not the standard of care in this disease, suggests that additional studies should be performed in a selected population.     

Chemotherapy for lung cancer

Chemotherapy is currently a primary treatment modality for small-cell lung cancer (SCLC). Combination chemotherapy of anticancer agents improves survival and mortality rather than chemotherapy with single agent. On the other hand, the role of chemotherapy in advanced non-small cell lung cancer(NSCLC) is still controversial. Several meta-analysis demonstrated a small but significant survival benefit of cisplatin-based chemotherapy. In the limited stage SCLC and locally advanced NSCLC, a combination of chemotherapy and thoracic irradiation was found to be superior to chemotherapy alone by several randomized trials and meta-analysis. Concurrent administration of anticancer agents with thoracic irradiation may be optimal treatment. In the last few years, several new agents have demonstrated antitumor activity against lung cancer and randomized trials of these drugs are now under way.     

Das kleinzellige Bronchialkarzinom

With about 20% of all lung cancers small cell lung cancer (SCLC) represents a major subset of this entity. Although therapeutic improvements did not receive as much attention as in non small cell lung cancer (NSCLC), many small steps of clinical progress have been achieved within the last 20 years. An optimal treatment should be based on an interdisciplinary treatment plan. The standard treatment in localized stages represents combined radiation and chemotherapy. Cisplatin and etoposide are in this concern considered as a gold standard. 3D-planned conformal radiotherapy should start as early as possible and should be applied concomitantly to chemotherapy and in certain cases even in a hyperfractionated treatment protocol. In very early stages surgical resection could be an option in selected cases. In advanced stages a platinum-based doublet offers high response rates. As already established in limited disease prophylactic cranial irradiation is now also indicated in extensive disease in case of any tumor remission. In the second line treatment and in patients with reduced performance status topotecan is recommended. Similar as in NSCLC pemetrexed might become an alternative treatment option in the second line setting. In the field of new targeted therapies bevacizumab achieved the most promising results. The present review highlights historical milestones and up-to-date trends in radiotherapy, chemotherapy and surgery. Furthermore, the role of experimental strategies and the management of certain special clinical situations are discussed.     

Front-line Therapy in Advanced Non–Small Cell Lung Cancer With Sensitive Epidermal Growth Factor Receptor Mutations: A Network Meta-analysis

PurposeSeveral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were firmly established as front-line treatment for non–small cell lung cancer (NSCLC) that harbored an activating EGFR mutation. Gefitinib or erlotinib was considered the standard of care. TKI-based combination therapy has been investigated and has shown encouraging results.MethodsThe PubMed and EMBASE databases, the Cochrane Central Register of Controlled Trials, and meeting abstracts were screened for relevant studies between January 2000 and February 2019. Prospective randomized controlled trials were included that investigated EGFR TKIs (alone or in combination) in untreated patients with NSCLC whose tumors had sensitive EGFR mutations. A frequentist random effects network meta-analysis model was conducted to assess objective response rate, progression-free survival, and overall survival. P-score was used to rank treatment effects.FindingsSeventeen trials involving 9 treatments and 4373 patients were included. Heterogeneity existed in the network analysis. For progression-free survival, the top 3 treatments were osimertinib, standard of care plus chemotherapy, and standard of care plus bevacizumab; corresponding p-scores were 0.88, 0.79, and 0.75, respectively. For overall survival, the top 3 treatments were standard of care plus chemotherapy, osimertinib, and dacomitinib; corresponding p-scores were 0.89, 0.85, and 0.64. TKI-based combination therapy caused more toxicity than a TKI alone.ImplicationsOsimertinib seemed to be a better option as upfront therapy for EGFR-mutant NSCLC in terms of efficacy and tolerability.     

Primary cytoreductive surgery for advanced ovarian cancer: is it the past, present, or future?

Ovarian cancer accounts for more deaths in the United States than all other gynecologic malignancies combined. This is largely due to the fact that no effective screening test has been identified thus far to facilitate early detection. As a result, two-thirds of women continue to be diagnosed with advanced stage III or IV disease. Historically, the standard of care has consisted of primary cytoreductive surgery-with an operative goal of achieving an optimal result with minimal residual disease-followed by adjuvant, platinum-based chemotherapy. However, data suggesting comparable efficacy of neoadjuvant chemotherapy and interval debulking has recently challenged this conventional dogma. The current decision-making on how to initially treat women with newly diagnosed advanced ovarian cancer has become increasingly controversial. This article focuses on whether primary cytoreductive surgery should remain the preferred method of management, or whether it is time for it to be superseded by neoadjuvant chemotherapy.     

Toripalimab in an advanced non-small cell lung cancer patient with poor general condition after multiline treatment: a case report

Several clinical trials have proven that immunotherapy can improve survival and benefit non-small cell lung cancer (NSCLC) patients. In patients who progress after chemotherapy, immune checkpoint inhibitor (ICI) monotherapy can prolong overall survival compared with patients receiving single-agent chemotherapy. A 61-year-old man diagnosed with advanced NSCLC and without driver variants received first-line chemotherapy but experienced recurrence. During subsequent treatment, the disease progressed rapidly, and his general condition deteriorated; therefore, toripalimab monotherapy was initiated. Surprisingly, he responded well, and symptoms were relieved after several treatment cycles despite pseudoprogression, shown in chest images. For driver gene-negative NSCLC patients who progress after chemotherapy and who develop poor performance status (PS), ICIs are an option to alleviate symptoms and improve survival. Furthermore, immunotherapy in patients with pseudoprogression may also provide a survival benefit.     

Neoadjuvant Chemotherapy in breast cancer

Neoadjuvant chemotherapy for breast cancer was originally used in locally advanced inoperable disease in order to achieve surgical resection. It was then extended to operable breast cancer with a view to downstaging tumors to facilitate breast-conserving surgery. Long-term results from randomized studies have shown no difference in disease-free or overall survival between neoadjuvant and adjuvant chemotherapy. The main benefit of neoadjuvant chemotherapy is its ability to downstage large tumors with a view to treatment by breast-conserving surgery. Since pathological complete response is thought to be main factor to achieve long-term survival, development of new agent or novel combination treatment is needed.