Clinical Benefit of Tyrosine Kinase Inhibitors in Advanced Lung Cancer with EGFR-G719A and Other Uncommon EGFR Mutations.

The optimal management of advanced non-small cell lung cancer (NSCLC) with noncanonical epidermal growth factor receptor (EGFR) mutations (i.e., exon 19 deletion and exon 21 L858R) is constrained by the heterogeneous behavior of individual uncommon mutations and limited prospective clinical data in this setting. Despite encouraging results with osimertinib from a recently published phase II trial from South Korea, afatinib remains the only currently approved drug for patients with tumors harboring uncommon EGFR mutations (i.e., S768I, L861Q, and/or G719X). When used at the standard dose of 40 mg daily, afatinib is associated with significant rates of treatment-related adverse events, leading to frequent dose reductions and treatment discontinuations. We report a case of a woman with advanced NSCLC harboring EGFR-G719A mutation treated with afatinib (at an off-label pulse dose strategy that merits further evaluation in prospective studies) with sustained partial response for 20 months with manageable expected toxicities. Subsequent disease progression was mediated by off-target pan-EGFR inhibitor (including osimertinib)-resistant KRAS mutation and not by acquisition of EGFR-T790M. We further present the current state of evidence in the literature behind use of first-, second-, and third-generation tyrosine kinase inhibitors and summarize the evolving spectrum of activity ascribed to osimertinib (and newer EGFR inhibitors with a more favorable therapeutic window and intracranial penetration) in this population of patients with advanced NSCLC and uncommon EGFR mutations. KEY POINTS: Uncommon EGFR mutations characterize a heterogeneous group of patients with advanced non-small cell lung cancer (NSCLC). Afatinib is the only currently U.S. Food and Drug Administration-approved drug for management of advanced NSCLC with uncommon EGFR mutations (S768I, L861Q, and/or G719X). Afatinib treatment at 40 mg daily is associated with high rates of adverse events and dose reductions; alternative strategies including pulse intermittent dosing should be evaluated prospectively. Osimertinib (with favorable safety profile and intracranial penetration) has shown promising results in this population in a phase II trial from South Korea; additional trials are ongoing.

Twelve tips for teaching oncology to non-oncologists.

Background: Teaching subspecialty care to trainees who are not pursuing that subspecialty poses many challenges. These challenges are amplified in the teaching of oncology to non-oncologists because there are more new therapies emerging in oncology than in any other discipline, and there are few oncologic issues managed by generalists without consultation. Concurrently, there is an increasing need for generalists to manage many aspects of care for patients with cancer.Aim: To provide 12 tips for oncologists to use to educate trainees on their oncology rotations.Method: The tips provided are based upon the available literature and the authors' own experience.Results: The 12 tips presented offer specific strategies for oncologists to enhance their teaching by selection of appropriate content and enhancing delivery. Focus is placed on aspects of oncology that trainees are likely to encounter as a generalist or non-cancer subspecialist. While oncology is used as the case study, these strategies are adaptable to any subspecialty area.Conclusion: Oncologists and other subspecialists can be core medical educators.

Clinical and laboratory features of autoimmune hemolytic anemia associated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICPis) are a novel class of immunotherapeutic agents that have revolutionized the treatment of cancer; however, these drugs can also cause a unique spectrum of autoimmune toxicity. Autoimmune hemolytic anemia (AIHA) is a rare, but often severe, complication of ICPis. We identified 14 patients from nine institutions across the United States who developed ICPi-AIHA. The median interval from ICPi initiation to development of AIHA was 55 days (interquartile range [IQR], 22-110 days). Results from the direct antiglobulin test (DAT) were available for 13 of 14 patients: 8 patients (62%) had a positive DAT and 5 (38%) had a negative DAT. The median pretreatment and nadir hemoglobin concentrations were 11.8 g/dL (IQR, 10.2-12.9 g/dL) and 6.3 g/dL (IQR, 6.1-8.0 g/dL), respectively. Four patients (29%) had a preexisting lymphoproliferative disorder, and two (14%) had a positive DAT prior to initiation of ICPi therapy. All patients were treated with glucocorticoids, with three requiring additional immunosuppressive therapy. Complete and partial recoveries of hemoglobin were achieved in 12 (86%) and 2 (14%) patients, respectively. Seven patients (50%) were rechallenged with ICPis, and one (14%) developed recurrent AIHA. Clinical and laboratory features of ICPi-AIHA were similar in DAT positive and negative patients. ICPi-AIHA shares many clinical features with primary AIHA; however, a unique aspect of ICPi-AIHA is a high incidence of DAT negativity. Glucocorticoids are an effective first-line treatment in the majority of patients with ICPi-AIHA, and most patients who are rechallenged with an ICPi do not appear to develop recurrence of AIHA.

Clinical coaching: Evolving the apprenticeship model for modern housestaff.

Feedback is one of the core components of teaching in the clinical setting. Traditionally, this activity has emphasized observations made by senior physicians and delivered to medical trainees. However, the optimal approach to feedback remains uncertain, and the literature abounds with trainee-perceived inadequacies in feedback content, quality, and impact. Moreover, given the multiplicity of demands on trainees and their physician mentors, we propose that medical trainees themselves-specifically, medical residents-are poised to serve as unique adjunct effectors of feedback. We propose a model of "clinical coaching" for residents as teachers, with emphasis on the active roles of both the feedback "giver" and "recipient". We define "clinical coaching" as "a helping longitudinal relationship between coach and apprentice that provides continuing feedback on and assistance with improving performance." Here, "coach" is the more experienced trainee (e.g. supervising resident), and "apprentice" is the less experienced trainee (e.g. intern or medical student). By working to better recognize and prepare residents for this vital role, we propose to encourage efforts to optimize the structure, execution, and impact of feedback in the contemporary climate of medical education.

Growing Pains: a Simulation-Based Curriculum for Improving the Transition to Hematology/Oncology Fellowship.

Trainee exposure to clinical oncology during residency training is heterogeneous and often modest. The steep learning curve upon entry into fellowship can result in undue stress for fellows and their patients. Simulation-based training has been shown to be superior to classical didactic approaches. We have introduced several innovative simulation-based workshops into the curriculum for the Johns Hopkins Hematology/Oncology Fellowship Training Program in order to address this unmet need. During the first months of training, fellows were engaged in activities emphasizing essential clinical and procedural skills. Specific workshops included the following: (1) chemotherapy writing, (2) cadaveric and simulation-based bone marrow biopsy and intrathecal chemotherapy administration, and (3) simulation-based communication skills training. All first-year fellows in our program participated in these exercises. Pre- and post-workshop surveys were administered to assess knowledge, attitudes, and behaviors; additional distant post-workshop evaluations were disseminated to assess the durability/impact of the curricula and for program evaluation. Overall, participating fellows indicated that the workshops improved patient care and comfort with procedures and patient-centered communication. Continued implementation of these workshops was recommended for program improvement. To the best of our knowledge, ours is amongst the first oncology fellowship training programs to systematically implement simulation-based curricula into our schema for fellowship training. We hypothesize that proactively introducing fellows to these high-yield activities will translate into improved patient care and reduced stress for trainees. Additional investigation into the long-term impact of such curricula remains an area of ongoing need.

Management of Treatment Resistance in Patients With Advanced Epidermal Growth Factor Receptor-Mutated Lung Cancer: Personalization, Parsimony, and Partnership.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.Patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer represent a distinct subgroup of individuals who can experience initially tolerable and durable effects with first-line EGFR-directed tyrosine kinase inhibitors. Unfortunately, acquired treatment resistance and cancer progression within the CNS are inevitable during the disease course and present a challenging transition in the care continuum. Next-line therapies generally require combinations of drugs and afford nuanced differences in clinical outcomes relative to the treatment experience, toxicity profile, and quality of life. Therapeutic stratification and modulation thus require further personalization and partnership with patients to identify key clinical, molecular, and human-specific factors to best guide optimal care.

Defining the Educational Needs for a Community-Based Hematology/Oncology Career: A National Needs Assessment.

PURPOSE: Little is known about the specific needs during training for hematology/oncology providers practicing in community-based settings. We conducted a national survey of hematologists/oncologists employed in community or academic-community hybrid settings to delineate their educational needs. METHODS: An electronic questionnaire was developed and distributed nationally through professional organizations. We primarily assessed whether survey participants received any specific training during fellowship for community-based practice. Participants were also surveyed regarding training experiences that might have affected their preparation. Relative risk (RR) and 95% CI were calculated using modified Poisson regression to identify factors associated with receiving training specifically for community-based settings. RESULTS: Of 125 participants from across 25 states, 63% were male and 58% identified as White. Less than half (41.6%, binomial 95% CI, 32.8 to 50.7) received any training in a community-based setting. Participants identified rotations in community settings (47%), direct mentorship from community-based physicians (40%), and longitudinal clinic in a community setting (36%) as experiences that would have been valuable. Specific curricula of interest included medical operations and administration (63%), health policy (35%), and quality improvement (27%). Respondents in clinical practice for <10 years were more likely to have received any training specifically for a community-based career (RR, 2.13 [95% CI, 1.18 to 3.86]). CONCLUSION: Our study demonstrates substantial unmet needs as they relate to deliberately training fellows destined for community-based careers. Prospective design of clinical training and curricula emphasizing longitudinal exposures to and key aspects of health care delivery in the community setting are paramount to achieving optimal goal-concordant hematology/oncology training during fellowship.

The Impact of On-Target Resistance Mediated by EGFR-T790M or EGFR-C797S on EGFR Exon 20 Insertion Mutation Active Tyrosine Kinase Inhibitors.

Introduction: Mechanisms of resistance to EGFR exon 20 insertion mutation active inhibitors have not been extensively studied in either robust preclinical models or patient-derived rebiopsy specimens. We sought to characterize on-target resistance mutations identified in EGFR exon 20 insertion-mutated lung cancers treated with mobocertinib or poziotinib and evaluate whether these mutations would or would not have cross-resistance to next-generation inhibitors zipalertinib, furmonertinib, and sunvozertinib. Methods: We identified mechanisms of resistance to EGFR exon 20 insertion mutation active inhibitors and then used preclinical models of EGFR exon 20 insertion mutations (A767_V769dupASV, D770_N771insSVD, V773_C774insH) plus common EGFR mutants to probe inhibitors in the absence/presence of EGFR-T790M or EGFR-C797S. Results: Mobocertinib had a favorable therapeutic window in relation to EGFR wild type for EGFR exon 20 insertion mutants, but the addition of EGFR-T790M or EGFR-C797S negated the observed window. Zipalertinib had a favorable therapeutic window for cells driven by EGFR-A767_V769dupASV or EGFR-D770_N771insSVD in the presence or absence of EGFR-T790M. Furmonertinib and sunvozertinib had the most favorable therapeutic windows in the presence or absence of EGFR-T790M in all cells tested. EGFR-C797S in cis to all EGFR mutations evaluated generated dependent cells that were resistant to the covalent EGFR tyrosine kinase inhibitors mobocertinib, zipalertinib, furmonertinib, sunvozertinib, poziotinib, and osimertinib. Conclusions: This report highlights that poziotinib and mobocertinib are susceptible to on-target resistance mediated by EGFR-T790M or -C797S in the background of the most prevalent EGFR exon 20 insertion mutations. Furmonertinib, sunvozertinib, and to a less extent zipalertinib can overcome EGFR-T790M compound mutants, whereas EGFR-C797S leads to covalent inhibitor cross-resistance-robust data that support the limitations of mobocertinib and should further spawn the development of next-generation covalent and reversible EGFR exon 20 insertion mutation active inhibitors with favorable therapeutic windows that are less vulnerable to on-target resistance.

A Real-World Study of Patient Characteristics and Clinical Outcomes in EGFR Mutated Lung Cancer Treated with First-Line Osimertinib: Expanding the FLAURA Trial Results into Routine Clinical Practice.

Osimertinib is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) that is used for first-line therapy in EGFR mutated non-small cell lung cancer (NSCLC) based on the results of the randomized FLAURA trial (ClinicalTrials.gov number NCT02296125). We performed a retrospective analysis of baseline characteristics and clinical outcomes in 56 real-world patients treated with osimertinib. In total, 45% of patients were determined to be FLAURA-eligible and 55% were FLAURA-ineligible based on the published inclusion/exclusion criteria of the aforementioned trial. For clinical outcomes, the median osimertinib time to treatment discontinuation (TTD) for all patients was 16.9 months (95% CI: 12.6-35.1), whereas the median TTD was 31.1 months (95% CI: 14.9-not reached) in the FLAURA-eligible cohort and the median TTD was 12.2 months (95% CI: 8.1-34.6 months) in the FLAURA-ineligible cohort. Re-biopsy at acquired resistance disclosed both on- and off-target mechanisms. The most common therapies following osimertinib included local therapies followed by post-progression osimertinib, platinum-doublet chemotherapy with or without osimertinib, and osimertinib combinatory targeted therapies. The median overall survival for all patients was 32.0 months (95% CI: 15.7-not reached), the median survival was not reached for the FLAURA-eligible cohort, and it was 16.5 months for the FLAURA-ineligible cohort. Our data support the use of osimertinib in real-word settings and highlight the need for designing registration trials that are more inclusive of patient/disease characteristics seen in routine clinical practice. It is yet to be determined if the use of evolving first-line EGFR inhibitor combination strategies (either platinum-doublet chemotherapy plus osimertinib or amivantamab plus lazertinib) will similarly translate from clinical trials to real-word settings.

Targeting the immune system in the treatment of non-small-cell lung cancer.

OPINION STATEMENT: Non-small-cell lung cancer (NSCLC) remains the most common cause of cancer-related death worldwide. Traditional cytotoxic agents and their attendant toxicities have remained the mainstay of systemic therapy for this disease, until now. With the identification of novel molecular and immune cancer-specific aberrancies, molecular agents and immunotherapies have garnered increasing attention as attractive targets, with the potential for improved outcomes while mitigating systemic toxicities seen with traditional cytotoxic agents. Despite a longstanding interest in immunotherapy for the treatment of NSCLC, results of prior studies of therapeutic vaccines have failed to show durable or convincingly meaningful clinical responses. However, newer trials of therapeutic vaccines and checkpoint inhibitors have yielded more promising results. In particular, the checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed death-1 (PD-1) pathway have shown meaningful clinical responses with manageable toxicities. Large phase III studies are underway, the results of which have the potential to revolutionize the way in which we care for patients with NSCLC. More studies also are needed to investigate the potentially synergistic effects of traditional and immune-based therapies. Given their unique antineoplastic effects, novel immune-specific clinical endpoints also are actively being investigated.

Massive Thymic Hyperplasia Masquerading as Cancer: A Case Report and Review of the Literature.

A 34-year-old woman presenting with abdominal pain, chest pressure, weight loss, and tachycardia was found to have an 11.4-cm anterior mediastinal mass associated with intrathoracic lymphadenopathy on chest computed tomography (Fig. 1A). Core needle biopsy was concerning for a type B1 thymoma. During this patient's initial workup, she was found to have both clinical and laboratory evidence of Graves' thyroiditis, raising diagnostic suspicion for thymic hyperplasia rather than thymoma. The case discussed here highlights the unique challenges that arise in the evaluation and management of thymic masses and serves as a prudent reminder that both benign and malignant disorders may present with mass-like changes.

EGFR exon 20 insertion mutations and ERBB2 mutations in lung cancer: a narrative review on approved targeted therapies from oral kinase inhibitors to antibody-drug conjugates.

Background and Objective: This review will provide an overview of EGFR and ERBB2 mutations in non-small-cell lung cancer (NSCLC) with a focus on recent clinical approvals. Methods: We obtained data from the literature in accordance with narrative review reporting guidelines. Key Content and Findings: EGFR mutations are present in up to 15-20% of all NSCLCs; amongst these, 10% correspond to kinase domain insertions in exon 20. Structurally similar, ERBB2 (HER2) mutations occurs in 1-4% of NSCLCs, mostly consisting of insertions or point mutations. The majority of EGFR exon 20 insertions occur within the loop following the regulatory C-helix and activate the kinase domain of EGFR without generating a therapeutic window to gefitinib, erlotinib, afatinib, dacomitinib or osimertinib. Mobocertinib represents a novel class of covalent EGFR inhibitors with a modest therapeutic window to these mutants and induces anti-tumor responses in a portion of patients [at 160 mg/day: response rate of <30% with duration of response (DoR) >17 months and progression-free survival (PFS) of >7 months] albeit with mucocutaneous and gastrointestinal toxicities. The bi-specific EGFR-MET antibody amivantamab-vmjw has modest but broad preclinical activity in EGFR-driven cancers and specifically for EGFR exon 20 insertion-mutated NSCLC has response rates <40% and PFS of <8.5 months at the cost of both infusion-related plus on-target toxicities. Both drugs were approved in 2021. The clinical development of kinase inhibitors for ERBB2-mutated NSCLC has been thwarted by mucocutaneous/gastrointestinal toxicities that preclude a pathway for drug approval, as the case of poziotinib. However, the activation of ERBB2 has allowed for repurposing of antibody-drug conjugates (ADCs) that target ERBB2 with cytotoxic payloads. The FDA approved fam-trastuzumab deruxtecan-nxki in 2022 for NSCLC based on response rate of >55%, DoR >9 months, PFS >8 months and manageable adverse events (including cytopenias, nausea and less commonly pneumonitis). Other therapies in clinical development include sunvozertinib and zipalertinib, among others. In addition, traditional cytotoxic chemotherapy has some activity in these tumors. Conclusions: The approvals of mobocertinib, amivantamab, and trastuzumab deruxtecan represent the first examples of precision oncology for EGFR exon 20 insertion-mutated and ERBB2-mutated NSCLCs.

ALK Deletion Exons 2 to 19: Case Report of a Rare ALK Inhibitor-Responsive Lung Cancer Driver Oncogene.

ALK internal deletions of nonkinase domain exons occur in 0.01% of lung cancers with ALK genomic aberrations. We report a lung adenocarcinoma with a previously undescribed somatic ALK deletion of exons 2 to 19 with dramatic and sustained (>23 mo) response to alectinib. Our and other reported cases with ALK nonkinase domain deletions (between introns and exons 1-19) can display positive results in nonsequencing-based lung cancer diagnostic tests (such as immunohistochemistry) used to screen for more common ALK rearrangements. This case report emphasizes that "ALK-driven" lung cancers should be expanded to encompass those harboring not only ALK rearrangements with other genes but also ALK nonkinase domain deletions.

EGFR exon 19 insertion EGFR-K745_E746insIPVAIK and others with rare XPVAIK amino-acid insertions: Preclinical and clinical characterization of the favorable therapeutic window to all classes of approved EGFR kinase inhibitors.

BACKGROUND: The epidermal growth factor receptor (EGFR)-K745_E746insIPVAIK and others with XPVAIK amino-acid insertions are exon 19 insertion mutations, which, at the structural modeling level, resemble EGFR tyrosine kinase inhibitor (TKI)-sensitizing mutants. An important unmet need is the characterization of therapeutic windows plus clinical outcomes of exon 19 XPVAIK amino-acid insertion mutations to available EGFR TKIs. METHODS: We used preclinical models of EGFR-K745_E746insIPVAIK and more typical EGFR mutations (exon 19 deletion, L858R, L861Q, G719S, A763_Y764insFQEA, other exon 20 insertion mutations) to probe representative 1st (erlotinib), 2nd (afatinib), 3rd generation (osimertinib), and EGFR exon 20 insertion active (mobocertinib) TKIs. We also compiled outcomes of EGFR exon 19 insertion mutated lung cancers-from our institution plus the literature-treated with EGFR TKIs. RESULTS: Exon 19 insertions represented 0.3-0.8% of all EGFR kinase domain mutation in two cohorts (n = 1772). Cells driven by EGFR-K745_E746insIPVAIK had sensitivity to all classes of approved EGFR TKIs when compared to cells driven by EGFR-WT in proliferation assays and at the protein level. However, the therapeutic window of EGFR-K745_E746insIPVAIK driven cells was most akin to those of cells driven by EGFR-L861Q and EGFR-A763_Y764insFQEA than the more sensitive patterns seen with cells driven by an EGFR exon 19 deletion or EGFR-L858R. The majority (69.2%, n = 26) of patients with lung cancers harboring EGFR-K745_E746insIPVAIK and other mutations with rare XPVAIK amino-acid insertions responded to clinically available EGFR TKIs (including icotinib, gefitinib, erlotinib, afatinib and osimertinib), with heterogeneous periods of progression-free survival. Mechanisms of acquired EGFR TKI resistance of this mutant remained underreported. CONCLUSIONS: This is the largest preclinical/clinical report to highlight that EGFR-K745_E746insIPVAIK and other mutations with exon 19 XPVAIK amino-acid insertions are rare but sensitive to clinically available 1st, 2nd, and 3rd generation as well as EGFR exon 20 active TKIs; in a pattern that mostly resembles the outcomes of models with EGFR-L861Q and EGFR-A763_Y764insFQEA mutations. These data may help with the off-label selection of EGFR TKIs and clinical expectations of outcomes when targeted therapy is deployed for these EGFR mutated lung cancers.

Training Hematologists/Oncologists for the Academic-Community Hybrid: Creating a Fellowship Framework for the Future.

PURPOSE: Conventional hematology/oncology fellowship training is designed to foster careers in academic practice through intensive exposure to clinical and laboratory research. Even so, a notable proportion of graduating fellows opt to pursue a clinically focused career outside the realm of academic medicine. Given the corresponding shortage of oncologists in nonurban and rural settings, improving the representation of hematologists/oncologists in the community setting is a national priority. METHODS: We reviewed current national challenges and changing models of cancer care delivery in the context of the traditional academic training model along with trends in practice patterns for recent hematology/oncology graduates. We defined the Academic-Community hybrid (ACH) and how it supports the evolution in contemporary models of cancer care. We then drew on the authors' experiences to formulate an innovative goal-concordant training paradigm for fellows seeking careers in the ACH model. RESULTS: The ACH hematology/oncology fellowship training pathway emphasizes and optimizes professional development domains including clinical care, patient safety and quality improvement, business and operations, cancer care equity and community access, healthy policy and alignment with professional organizations, and medical education. CONCLUSION: This novel hematology/oncology training model provides a paradigm for optimizing preparedness for practice in an increasingly complex cancer care delivery environment while addressing workforce shortages and health disparities.

Moving From Theory to Practice in Oncology Education When Virtual Is Your Reality.

Evidence-based education is crucial for meeting the evolving needs of learners in the oncology workforce, given the growing demand for well-trained providers and the rapidly changing complexities of cancer care. With the onset of the severe acute respiratory syndrome coronavirus 2 pandemic, innovative means of delivering educational content in a virtual setting have become a necessary reality. Knowledge of learning science can be translated into concrete, pragmatic methods for using evidence-based education in a virtual world and affords important opportunities for innovation and inclusion across a broad network of educators and learners. We offer key insights and tools to promote attention to and agility with teaching in virtual settings to meet the needs of contemporary educators and learners.

Oncology Fellows' Clinical Discussions, Perceived Knowledge, and Formal Training Regarding Medical Cannabis Use: A National Survey Study.

PURPOSE: Evidence suggests that patients with cancer frequently use cannabis with medicinal intent and desire clinical guidance from providers. We aimed to determine whether oncology training adequately prepares fellows to discuss medical cannabis. METHODS: A national survey study was conducted from January to March 2021. A questionnaire assessing oncology fellows' practices regarding cannabis recommendations in cancer care and their knowledge of its effectiveness and risks compared with conventional care for cancer-related symptoms was developed and sent to 155 US-based oncology training programs to distribute to trainees. RESULTS: Forty programs from 25 states participated; of the 462 trainees across these programs, 189 responded (response rate of 40%). Of the participants, 52% were female; 52% were White, 33% Asian, and 5% Hispanic. Fifty-seven percent reported that they discussed medical cannabis with more than five patients in the preceding year; however, only 13% felt sufficiently informed to issue cannabis-related clinical recommendations. Twenty-four percent reported having received formal training regarding medical cannabis. Oncology fellows who reported having received prior training in medical cannabis were significantly more likely to discuss cannabis with patients (risk ratio: 1.37, 95% CI 1.06 to 1.75; P = .002) and feel sufficiently informed to discuss cannabis recommendations (risk ratio: 5.06; 95% CI, 2.33 to 10.99; P < .001). Many viewed the botanical as a useful adjunctive therapy that was at least as effective as conventional treatments for anorexia/cachexia (72%), nausea/vomiting (45%), and pain (41%). CONCLUSION: Most oncology trainees not only reported engaging in discussions regarding medical cannabis with patients but also considered themselves insufficiently informed to make cannabis-related clinical recommendations. The discrepancy between the frequency of cannabis inquiries/discussions at the patient level and comfort/knowledge at the trainee provider level represents an unmet curricular need with implications for both graduate medical education and patient care.

Complete pathologic response to short-course neoadjuvant alectinib in mediastinal node positive (N2) ALK rearranged lung cancer.

OBJECTIVES: Neoadjuvant therapy prior to surgical resection for locally advanced lung cancer has evolved to incorporate systemic cytotoxic chemotherapy +/- immunotherapy +/- radiotherapy. The role of neoadjuvant precision therapies remains understudied. MATERIALS AND METHODS: We report cases with major and complete pathologic responses to off-label neoadjuvant alectinib. RESULTS: A case with stage IIIA (cT1b cN2 cM0) EML4-ALK variant 3a/b lung adenocarcinoma received 6 weeks of alectinib followed by R0 left upper lobectomy with complete pathological response (ypT0 ypN0). Another case with stage IIIA (cT3 cN2 cM0) EML4-ALK variant 2 received 12 weeks of alectinib followed by R0 right middle lobectomy with a major pathologic response (ypT1a ypN0) but systemic recurrence 12 months post-operatively. CONCLUSION: Ongoing clinical trials are evaluating the role of both neoadjuvant and adjuvant ALK-directed therapy. Our cases support the completion of ongoing trials (ALINA: NCT03456076 and ALNEO: NCT05015010), and highlight the ability of second generation ALK inhibitors to induce major and complete pathologic responses in the neoadjuvant setting plus the likely role of long-term adjuvant kinase inhibitor therapy to prevent radiographic/clinical recurrence.