Brief Report on Global Clinician Practices in the First-Line Management of Metastatic Non-Small Cell Lung Cancer.

INTRODUCTION: In the dynamic landscape of metastatic NSCLC (mNSCLC) management, marked by several frontline options and the integration of next generation sequencing (NGS) for informed decision-making, barriers persist despite advancements. This includes challenges in clinical trial recruitment. To gain global insights into clinicians' practices, we conducted a survey on their testing and management approaches for patients with mNSCLC. METHODS: The survey, conducted from July 12 to August 20, 2023, utilized multiple-choice questions and qualitative research questions, employing the Likert Scale for comprehensive insights. RESULTS: A total of 127 individuals responded, with 72% affiliated with academic health systems, and 55% practicing in the USA. Regarding testing practices, 93% consistently ordered NGS for non-squamous histology, while 54% did so for squamous cell histology. Concurrent tissue and liquid biopsies were routinely ordered by 28%, while 39% reported ordering both testing platforms concurrently for select cases only. Respondents cited logistical barriers, such as insufficient tissue and lack of infrastructure, as the most common hindrance to molecular testing (76%), followed by reimbursement challenges (56%) and concerns about delayed turnaround time (50%). While most respondents were confident in interpreting NGS results, 22% lacked confidence. Concerning treatment decisions, 72% preferred awaiting molecular testing results before initiating systemic therapy. Less than 50% routinely referred patients for clinical trials in the frontline setting for mNSCLC. For patients with disease expressing high PD-L1 levels, most oncologists preferred pembrolizumab monotherapy. For disease with low PD-L1 expression, a platinum doublet chemotherapy regimen combined with pembrolizumab was favored. In disease cases with negative PD-L1 expression, a platinum doublet chemotherapy regimen with pembrolizumab was preferred. Key factors influencing oncologists' preferred immune checkpoint inhibitor (ICI) included experience with one ICI over another, preferred status per national guidelines, availability of trial data with a significant follow-up period, and consideration of drug cost. CONCLUSION: Although this study demonstrates an improved awareness and adoption of ordering NGS for the management of mNSCLC, it underscores the persistence of various barriers that must be addressed to improve upon the quality of care for patients diagnosed with mNSCLC.

Clinical Trials for Patients With Cancer.

This JAMA Oncology Patient Page explains clinical trials and what patients should consider regarding enrollment.

The Democratization of Hematology-Oncology Medical Education during the COVID-19 Pandemic.

Like many other aspects of hematology-oncology training, medical education experienced rapid changes throughout the COVID-19 pandemic that continue until today. We discuss some of the most transformative areas within medical education, including, but not limited to, educational philosophy; use of virtual resources; inter-institutional connections, shifts in clinical training; changes in recruitment practice; and attention to equity and diversity. Moreover, we add our own experiences to complement the limited literature addressing these topics. We conclude by highlighting some of the benefits of this unprecedented transformation in democratizing medical education that we hope endure beyond the pandemic.

Clinical outcomes of immunotherapy continued beyond radiographic disease progression in older adult patients with advanced non­small cell lung cancer.

Immunotherapy is an effective and generally well-tolerated treatment strategy for older adult patients (aged ≥70 years) with advanced non-small cell lung cancer (NSCLC). Unfortunately, most patients who receive immunotherapy eventually exhibit disease progression during treatment. The present study reports on a subset of older adult patients with advanced NSCLC who could effectively continue immunotherapy beyond radiographic disease progression due to perceived clinical benefit. Local consolidative radiotherapy may be used in select older adult patients to prolong the duration of immunotherapy they receive, with a particular consideration of their preexisting co-morbidities, performance status and tolerance of potential toxicities associated with combined modality therapy. However, prospective research is needed to determine which patients benefit most from the addition of local consolidative radiotherapy, including whether type of disease progression (i.e., sites of progression, pattern of progression) and/or extent of consolidation offered (i.e., complete or incomplete) impact clinical outcomes. Further research is also warranted to determine which patients would most benefit from the continuation of immunotherapy beyond documented radiographic disease progression.

The Multidisciplinary Cancer Conference.

This JAMA Oncology Patient Page explains multidisciplinary cancer conferences and their benefits.

Lung Cancer Treatment Advances in 2022.

The therapeutic landscape of lung cancer treatment is changing rapidly, and new data was presented at the recently concluded American Society of Clinical Oncology 2022 (ASCO22) meeting. We highlight studies of clinical relevance that represent significant updates in the current management of non-small cell lung cancer (SCLC) and small cell lung cancer (NSCLC). We summarize the updates in early-stage NSCLC, mutated and non-mutated advanced NSCLC as well as small cell lung cancer (SCLC), and discuss these advances in the context of the current clinical standard of care.

Clinical Effectiveness and Safety of Anti-PD-(L)1 Therapy Among Older Adults With Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: As a result of the approval of several immune checkpoint inhibitors (ICIs) for the treatment of non-small cell lung cancer (NSCLC), many older adults are being treated with ICIs. Older adults are underrepresented in most pharmaceutical clinical trials. Therapy outcomes in this population with ICIs is particularly important since, age related factors may have an influence on the immune system. METHODS: We utilized the MD Anderson Cancer Center Gemini Team's Lung Cancer Database to retrospectively study patients ≥70 years of age with advanced NSCLC treated with anti-PD-(L)1 monotherapy to look at the clinical outcomes. RESULTS: 179 patients met the inclusion criteria for this retrospective analysis. There were 106 men and 73 women. The median age of the cohort was 74.9 years, and overall survival was 20.6 months. 27.6% of all patients had an objective response to therapy. In 33 patients who had radiological progression, treatment continued beyond progression due to clinical benefit. In this group, 6 patients had subsequent improvement in radiologic assessment. Age groups were not significantly associated with differences in clinical outcomes. CONCLUSIONS: This study suggests that anti-PD-(L)1 monotherapy is effective and well tolerated among older adults with advanced NSCLC. While pseudoprogression is rare, treatment beyond progression may provide clinical benefit in a subset of patients and warrants further investigation.

Narrative review of the emerging role of molecular biomarkers in guiding the definitive management of unresectable non-small cell lung cancer.

The addition of PD-L1 targeting consolidation therapy to previously standard of care concurrent chemoradiation for locally advanced, unresectable non-small cell lung cancer resulted in dramatic improvements in clinical outcomes. However, in contrast to patients with metastatic disease, the application of immunotherapies is not currently guided by molecular characteristics of patient tumors. Furthermore, despite increasing awareness of predictive and/or prognostic genomic alterations in patients with locally advanced disease, the utility of targeted therapies, such as those aimed at alterations in EGFR or ALK, remains unclear in this subset of patients. As a result, patients with unresectable, locally advanced non-small cell lung cancer are treated uniformly according to histology, regardless of other molecular features despite the potential for treatment-associated risks without a clear benefit. Here, we first discuss the advantages of utilizing molecular biomarkers to guide treatment of non-small cell lung cancer based on treatment outcomes in the metastatic setting. Next, we review preclinical and retrospective clinical data that supports potential further personalization of these treatment strategies in earlier stages of disease. Finally, we discuss some of the ongoing clinical trials attempting to address these hypotheses prospectively.

Medical Hematology/Oncology Fellows' Perceptions of Online Medical Education During the COVID-19 Pandemic.

In response to the COVID-19 social distancing guidelines, residency and fellowship programs transitioned to virtual instruction to deliver didactics and continue with medical education. The efficacy of such a fully online learning environment, however, remains unknown. To investigate its impact on medical education, this study surveyed hematology/oncology fellows at The University of Texas MD Anderson Cancer Center on their attitudes regarding the online-based lecture program. Fellows were emailed a 19-question survey with questions on demographics, ease of technical access to the online platform, level of comfort with participation, knowledge acquisition, wellness, and COVID-19-specific coverage. A free-text question soliciting ways to improve upon online learning was also included. The response rate was 71% (30/42). Most respondents reported easy/very easy accessibility to the online environment. Seventy-seven percent of the participants did not experience a technical issue. Seventy percent felt comfortable/very comfortable with participating in the conference. Thirty-seven percent felt comfortable/very comfortable with actively offering an answer to questions during the interactive board review session. Eighty-seven percent would have been more willing to offer an answer during the board review session if an anonymous poll format was utilized. Sixty-three percent felt they learned the same amount as they typically do during an in-person session. Thirty-three percent reported they were less focused as compared with an in-person session. One hundred percent of the participants had their questions answered, either at all times (87%) or sometimes (13%). Sixty percent experienced a change in social interactions as compared with an in-person session. Fifty-four percent reported that it was easy/very to balance online attendance despite personal/family commitments. One hundred percent appreciated the flexibility of the online learning environment. Ninety percent felt safer at home attending these lectures compared with receiving these lectures in-person during the COVID-19 pandemic. Overall, most fellows felt comfortable with the transition to a fully online learning environment. Strategies to encourage active participation, enhance social interaction, and provide additional flexibility are still needed.

Advanced Non-Small Cell Lung Cancer: Sequencing Agents in the EGFR-Mutated/ALK-Rearranged Populations.

Personalized therapy based on actionable molecular markers has completely transformed the therapeutic landscape in advanced non-small cell lung cancer (NSCLC). In less than 15 years, multiple molecular targets, led by EGFR and anaplastic lymphoma kinase (ALK), have been identified, and myriad oral tyrosine kinase inhibitors (TKIs) are now available to target these oncogenic drivers, with the expectation that the majority of patients will respond to treatment and that progression-free survival (PFS) will exceed 10 to 30 months, far better than we observed historically with chemotherapy alone. As a result, prognosis has improved dramatically in this subset of patients. Osimertinib has largely displaced first- and second-generation EGFR TKIs, including gefitinib, erlotinib, and afatinib, in the management of EGFR-mutated NSCLC. PFS now exceeds 18 months, and central nervous system penetrance is enhanced. Dacomitinib has the distinction of being the first EGFR TKI to demonstrate a survival advantage compared with older TKIs. Recent data suggest therapeutic additivity, if not synergy, for the concurrent use of chemotherapy, as well as monoclonal antibodies targeting angiogenesis, with EGFR TKIs. Alectinib and brigatinib, very specific ALK inhibitors, have proven superior to the erstwhile standard crizotinib in treatment-naive ALK+ NSCLC; PFS now routinely exceeds 2 to 3 years. In addition, these newer agents have far superior central nervous system penetration. As a result, many patients with ALK+ advanced NSCLC with brain metastases, even some who are symptomatic, can defer or indefinitely avoid brain irradiation. Mechanisms of resistance in ALK are complicated, with multiple new agents being developed in this arena. Although many patients with molecular targets can reasonably expect to live 5 years or more, the emergence of molecular resistance is virtually inevitable. In this regard, systemic platinum-based chemotherapy is the final common therapeutic pathway for virtually all patients with oncogenic drivers. Standard regimens include pemetrexed and carboplatin, as well as the E4599 regimen, combination solvent-based paclitaxel, carboplatin, and bevacizumab. Checkpoint inhibitors, as single agents, have not yielded much benefit, even in those with high levels of PD-L1 expression. However, in a subanalysis of patients with ALK and EGFR mutations enrolled in IMpower150, the addition of atezolizumab to the E4599 regimen led to a major overall survival benefit (hazard ratio < 0.40). In the absence of systemic chemotherapy, combining checkpoint inhibitors with TKIs in this setting remains investigational; several studies have demonstrated untoward pulmonary and hepatic toxicity.

Palliative Care Referrals for Advanced Non-small-cell Lung Cancer (NSCLC): Patient and Provider Attitudes and Practices.

BACKGROUND: Early palliative care (PC) improves quality of life and prolongs survival for patients with metastatic non-small cell lung cancer (NSCLC). Despite these benefits, patient- and provider-specific barriers lead to underutilization of PC. To investigate these barriers, this 2 part study surveyed United States oncologists and patients with NSCLC. PATIENTS AND METHODS: Oncologists in the International Association for the Study of Lung Cancer membership directory were surveyed on referral practice and attitudes regarding the role of PC for patients with NSCLC. Patients with advanced NSCLC at the Vanderbilt Ingram Cancer Center were surveyed separately regarding their understanding of PC and factors influencing them to seek referral. RESULTS: Of 279 oncologists, 93 responded. Eighty-three percent believe definitive evidence exists supporting early PC; however, in practice, oncologists only refer an average of 19% of patients at diagnosis. Reasons for not referring included lack of symptoms (56%), belief that oncologists can manage PC independently (46%), not wanting to burden patients with appointments (41%), concern that referral may not be well received (38%), and long wait times (20%). Of 100 patients with NSCLC, 64% were unfamiliar with PC. Six percent had seen a PC provider. Ninety-eight percent of patients would accept referral if recommended by their oncologist. Patients desired referral for uncontrolled pain (95%), weak support system (86%), other cancer-related symptoms (85%), goals of care discussion (76%), and depression/anxiety (76%). CONCLUSION: Although most oncologists acknowledge benefits of early PC for patients with metastatic NSCLC, a minority of patients are referred. Few patients with NSCLC are familiar with PC, but most are interested in referral.

Metastatic Soft Tissue Sarcomas: A Review Of Treatment and New Pharmacotherapies.

Soft tissue sarcomas represent a group of heterogeneous mesenchymal tumors that occur rarely in adults. While a variety of histological subtypes exist, some of the most common are leiomyosarcoma and liposarcoma. For eligible patients, standard first-line treatment of metastatic disease has typically comprised anthracycline-containing regimens. While traditional cytotoxic chemotherapy has been the mainstay of treatment in metastatic soft tissue sarcoma, emerging targeted and novel therapies are creating new frontiers of treatment for a variety of histological subtypes. Olaratumab (Lartruvo, Eli Lilly) in combination with doxorubicin represents a new potential first-line treatment option. Second-line therapy is often histology-driven, and novel treatment options include trabectedin (Yondelis, Janssen) and eribulin (Halaven, Eisai). This review discusses the diagnosis, role of chemotherapy in unresectable and metastatic disease, and role of emerging therapies in the treatment of metastatic soft tissue sarcoma.

Background and rationale of the eXalt3 trial investigating X-396 in the treatment of ALK+ non-small-cell lung cancer.

Despite significant advancements in the treatment of anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer (NSCLC) since the advent of crizotinib, the development of acquired resistance and poor CNS efficacy have necessitated the search for novel and more robust therapies. Ensartinib (X-396) is a novel second-generation ALK-tyrosine kinase inhibitor (TKI) that holds much clinical promise. Preclinical data have demonstrated increased potency of the drug as compared with crizotinib and other second-generation ALK-TKI therapies such as alectinib and ceritinib. This review highlights the first- and second-generation ALK inhibitors approved for the treatment of ALK-positive NSCLC and discusses the clinical trial protocol for the eXalt3 trial (NCT02767804) comparing the efficacy and safety of ensartinib to crizotinib in patients diagnosed with ALK-positive NSCLC who are naive to prior ALK-TKI treatment.