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The European Society for Medical Oncology (ESMO) held a virtual consensus-building process on epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer in 2021. The consensus included a multidisciplinary panel of 34 leading experts in the management of lung cancer. The aim of the consensus was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where the available evidence is either limited or conflicting. The main topics identified for discussion were: (i) tissue and biomarkers analyses; (ii) early and locally advanced disease; (iii) metastatic disease and (iv) clinical trial design, patient's perspective and miscellaneous. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. • A virtual consensus on the management of EGFR-mutant NSCLC was organized by the ESMO, including 34 experts from 18 countries. • The experts compiled recommendations with supporting evidence on controversial topics about the EGFR-mutant lung cancer. • Recommendations were formulated for tissue and biomarkers analyses; early, locally advanced and metastatic disease; miscellaneous. [ABSTRACT FROM AUTHOR]

Targeting the epidermal growth factor receptor (EGFR) pathway has become standard practice for the treatment of advanced non-small-cell lung cancer. Compared with chemotherapy, egfr tyrosine kinase inhibitors (TKIS) have been associated with improved efficacy in patients with an EGFR mutation. Together with the increase in efficacy comes an adverse event (AE) profile different from that of chemotherapy. That profile includes three of the most commonly occurring dermatologic aes: acneiform rash, stomatitis, and paronychia. Currently, no randomized clinical trials have evaluated the treatments for the dermatologic aes that patients experience when taking egfr tkis. Based on the expert opinion of the authors, some basic strategies have been developed to manage those key dermatologic aes. Those strategies have the potential to improve patient quality of life and compliance and to prevent inappropriate dose reductions. [ABSTRACT FROM AUTHOR]

Based on the results of a multicenter, open-label, phase II study conducted among patients with previously treated, advanced NSCLC, the combination of everolimus 5 mg/day plus erlotinib 150 mg/day does not warrant further investigation in light of increased toxicity and lack of substantial improvement in disease stabilization compared with erlotinib monotherapy.Background Preclinical data suggest combining a mammalian target of rapamycin inhibitor with erlotinib could provide synergistic antitumor effects in advanced non-small-cell lung cancer (NSCLC). Patients and methods In this multicenter, open-label, phase II study, patients with advanced NSCLC that progressed after one to two previous chemotherapy regimens were randomized 1:1 to erlotinib 150 mg/day ± everolimus 5 mg/day. Primary end point was the disease control rate (DCR) at 3 months; secondary end points included progression-free survival (PFS) and safety. Results One hundred thirty-three patients received everolimus–erlotinib (n = 66) or erlotinib alone (n = 67). The DCR at 3 months was 39.4% and 28.4%, respectively. The probability for the difference in disease control at 3 months to be ≥15% was estimated to be 29.8%, which was below the prespecified probability threshold of ≥40%. Median PFS was 2.9 and 2.0 months, respectively. Grade 3/4 adverse events occurred in 72.7% and 32.3% of patients, respectively. Grade 3/4 stomatitis was observed in 31.8% of combination therapy recipients. Conclusions Everolimus 5 mg/day plus erlotinib 150 mg/day was not considered sufficiently efficacious per the predefined study criteria. The combination does not warrant further investigation based on increased toxicity and the lack of substantial improvement in disease stabilization. [ABSTRACT FROM AUTHOR]

Metastatic non-small-cell lung cancer (NSCLC) is the leading cause of cancer mortality in Canada. Although treatment outcomes in advanced disease remain modest, with paradigm shifts in the approach to treatment, they are steadily improving. Customizing treatment based on histology and molecular typing has become the standard of care. EGFR genotyping and pathology subtyping should be considered routine in new diagnoses of metastatic NSCLC. Treatment options for those with somatic EGFR activating mutations include gefitinib until progression, followed by standard chemotherapy. For patients with wild-type EGFR, or in patients whose EGFR genotype is unknown, platinum-based chemotherapy remains the firstline standard, with single-agent chemotherapy as an option for older patients and those who are unfit for platinum-doublet therapy. Patients with nonsquamous histology may receive treatment regimens incorporating pemetrexed or bevacizumab. In patients with squamous cell carcinoma, the latter agents should be avoided because of concerns about enhanced toxicity or decreased efficacy. Secondline chemotherapy is offered to a selected subgroup of patients upon progression and may include pemetrexed in non-squamous histology and docetaxel or erlotinib (or both) in all histologies. Currently, only erlotinib is offered as a third-line option in unselected nsclc patients after failure of first- and second-line chemotherapy. Maintenance therapy is emerging as a new option for patients, as are targeted therapies for particular molecular subtypes of nsclc, such as crizotinib in tumours harbouring the EML4-ALK gene rearrangement. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab provides clinical benefit in multiple solid tumours, but is associated with some increase in bleeding risk. Thrombotic events necessitating therapeutic anticoagulation (TA) are common in cancer. This report describes the safety of concurrent bevacizumab and TA in three large placebo-controlled clinical studies.Methods: Study 1 (metastatic colorectal cancer (mCRC)), study 2 (mCRC), and study 3 (advanced non-small cell lung cancer) were blinded phase III studies. Eligibility criteria excluded patients on TA. Patients on protocol treatment who developed thrombotic events requiring TA were permitted to continue bevacizumab or placebo under specified conditions. Adverse events in patients who received bevacizumab and TA concurrently were assessed using the NCI-CTCAE scale.Results: While experience is limited, venous thrombotic events were the most common reason for TA initiation in the three studies. Severe bleeding event rates for patients receiving TA in the bevacizumab-treated groups were similar in frequency to the placebo groups, ranging from 0 to 8% or 0 to 67 events per 100 patient-years. No severe pulmonary bleeding was reported in any of the TA-treated populations.Conclusions: These data suggest that bevacizumab did not increase the risk of severe bleeding in cancer patients who received TA. [ABSTRACT FROM AUTHOR]

We developed a decision aid (DA) for patients with metastatic non-small cell lung cancer (NSCLC), to better inform patients of their prognosis and treatment options, and facilitate involvement in decision-making. In a pilot study, 20 patients with metastatic NSCLC attending outpatient clinics at a major cancer centre, who had already made a treatment decision, reviewed acceptability of the DA. The median age of the patients was 61 years (range 37-77 years), 35% were male, 20% had a university education, and most (75%) had English as a first language. Most had received chemotherapy, with 65% currently on treatment. Patients were not anxious at baseline and had clear understanding of the goals and toxicity of chemotherapy in advanced NSCLC. After reviewing the DA, patients' anxiety decreased slightly (P=0.04) and knowledge scores improved by 25% (P<0.001). Most improvements in understanding were of prognosis with and without chemotherapy, although patients still believed advanced NSCLC to be curable. Patients rated the DA highly with respect to information clarity, usefulness and were positive about its use in practice, although 40% found the prognostic information slightly upsetting. The DA for advanced NSCLC is feasible, acceptable to patients and improves understanding of advanced NSCLC without increasing patient anxiety. [ABSTRACT FROM AUTHOR]

Tumours with sensitizing mutations in the EGFR gene constitute a distinct molecular subgroup of non-small-cell lung cancers (nsclcs) that benefit from precision medicine. First- and second-generation epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are recommended as upfront therapy for EGFR-mutated advanced nsclc and, compared with chemotherapy, have resulted in superior progression-free survival, improved tumour response rates, and improved quality of life. However, resistance inevitably develops, and the third-generation tki osimertinib has been approved to target the gatekeeper EGFR mutation T790M, which is responsible for resistance in 60% of cases. Multiple drivers of tki resistance have now been identified, and many new drugs are in development. With respect to this rapidly evolving field, our review highlights the current status of treatment options for patients with EGFR-mutated advanced nsclc, focusing especially on identified causes of resistance, challenges, and clinical trials aiming to improve outcomes in this patient population. [ABSTRACT FROM AUTHOR]

The article discusses the diagnosis of lung cancer in 2015. Some of the challenges facing clinicians given the recent advances in the field of lung cancer had been highlighted. The optimization of current lung cancer diagnostic efforts has been aimed so that patients can be provided with the most appropriate, timely, and efficient diagnostic testing that allows them to benefit from a growing number of novel therapies and that improves patient outcomes.

• Non-small cell lung cancer (NSCLC) patients with single organ metastases (SOM) tends to have better overall survival than those with multiple organ metastases (MOM). • NSCLC patients with SOM exhibit distinct metastasis patterns and molecular profiles compared to those with MOM. • NSCLC SOM treatments vary by metastatic site. Studies would be beneficial to identify tailored treatment plans to optimize outcomes for this group. • Future studies should include SOM as a distinct category for NSCLC cases in survival analysis and consider it as a stratification factor in clinical trials. There is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). This retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. Of 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47–0.66, p < 0.001). In NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future. [ABSTRACT FROM AUTHOR]

New drugs such as pemetrexed, the epidermal growth factor receptor (EGFRC) tyrosine kinase inhibitors, and the Alk inhibitor crizotinib have recently enabled progress in the management of advanced non-smallcell lung cancer (NSCLC). More drugs, especially Met inhibitors, will follow. However, the benefits of these agents are not uniform across the spectrum of NSCLC, and optimizing their utility requires some degree of subgrouping of nsclc by the presence or absence of certain biomarkers. The biomarkers of current or imminent value are EGFR and KRAS mutational status, ALK rearrangements, and MET immunohistochemistry. As a predictor of benefit for anti-egfr monoclonal antibodies, EGFR immunohistochemistry is also of potential interest. Some of the foregoing biomarkers (EGFR, ALK, MET) are direct drivers of the malignant phenotype. As such, they are, quite rationally, the direct targets of inhibitory drugs. However, KRAS, while definitely a driver, has resisted attempts at direct pharmacologic manipulation, and its main value might lie in its role as part of an efficient testing algorithm, because KRAS mutations appear to exclude EGFR and ALK mutations. The indirect value of KRAS in determining sensitivity to other targeted agents or to pemetrexed remains controversial. The other biomarkers (EGFR, ALK, MET) may also have indirect value as predictors of sensitivity to chemotherapy in general, to pemetrexed specifically, and to radiotherapy and molecularly targeted agents. These biomarkers have all enabled the co-development of new drugs with companion diagnostics, and they illustrate the paradigm that will govern progress in oncology in the immediate future. However, in nsclc, the acquisition of sufficient biopsy material remains a stubborn obstacle to the evolution of novel targeted therapies. [ABSTRACT FROM AUTHOR]

Purpose: Slow accrual to cancer clinical trials impedes the progress of effective new cancer treatments. Poor physician-patient communication has been identified as a key contributor to low trial accrual. Question prompt lists (QPLs) have demonstrated a significant promise in facilitating communication in general, surgical, and palliative oncology settings. These simple patient interventions have not been tested in the oncology clinical trial setting. We aimed to develop a targeted QPL for clinical trials (QPL-CT).Method: Lung, breast, and prostate cancer patients who either had (trial experienced) or had not (trial naive) participated in a clinical trial were invited to join focus groups to help develop and explore the acceptability of a QPL-CT. Focus groups were audio-recorded and transcribed. A research team, including a qualitative data expert, analyzed these data to explore patients' decision-making processes and views about the utility of the QPL-CT prompt to aid in trial decision making.Results: Decision making was influenced by the outcome of patients' comparative assessment of perceived risks versus benefits of a trial, and the level of trust patients had in their doctors' recommendation about the trial. Severity of a patient's disease influenced trial decision making only for trial-naive patients.Conclusion: Although patients were likely to prefer a paternalistic decision-making style, they expressed valuation of the QPL as an aid to decision making. QPL-CT utility extended beyond the actual consultation to include roles both before and after the clinical trial discussion. [ABSTRACT FROM AUTHOR]

The advent of personalized therapy for non-small-cell lung carcinoma (nsclc) has improved patient outcomes. Selection of appropriate targeted therapy for patients with nsclc now involves testing for multiple biomarkers, including EGFR. EGFR mutation status is required to optimally treat patients with NSCLC, and thus timely and accurate biomarker testing is necessary. However, in Canada, there are currently no standardized processes or methods in place to ensure consistent testing implementation. That lack creates challenges in ensuring that all appropriate biomarkers are tested for each patient and that the medical oncologist receives the results for making informed treatment decisions in a timely way. An expert multidisciplinary working group was convened to create consensus recommendations about biomarker testing in advanced NSCLC in Canada, with a primary focus on EGFR testing. Recognizing that there are biomarkers beyond EGFR that require timely identification, the expert multidisciplinary working group considered EGFR testing in the broader context of integration into complex lung biomarker testing. Primarily, the panel of experts recommends that all patients with nonsquamous nsclc, regardless of stage, should undergo comprehensive reflex biomarker testing at diagnosis with targeted next-generation sequencing. The panel also considered the EGFR testing algorithm and the challenges associated with the pre-analytic, analytic, and post-analytic elements of testing. Strategies for funding testing by reducing silos of single biomarker testing for EGFR and for optimally implementing the recommendations presented here and educating oncology professionals about them are also discussed. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitors (tkis) have dramatically improved the survival of patients with ALK-rearranged (ALK+) non-small-cell lung cancer (nsclc). Clinical trial data can generally compare drugs in a pair-wise fashion. Real-world collection of health utility data, symptoms, and toxicities allows for the direct comparison between multiple tki therapies in the population with ALK+ nsclc. Methods: In a prospective cohort study, outpatients with ALK+ recruited between 2014 and 2018, treated with a variety of tkis, were assessed every 3 months for clinico-demographic, patient-reported symptom and toxicity data and EQ-5D-derived health utility scores (hus). Results: In 499 longitudinal encounters of 76 patients with ALK+ nsclc, each tki had stable longitudinal hus when disease was controlled, even after months to years: the mean overall hus for each tki ranged from 0.805 to 0.858, and longitudinally from 0.774 to 0.912, with higher values associated with second- or third-generation tkis of alectinib, brigatinib, and lorlatinib. Disease progression was associated with a mean hus decrease of 0.065 (95% confidence interval: 0.02 to 0.11). Health utility scores were inversely correlated to multiple symptoms or toxicities: rho values ranged from -0.094 to -0.557. Fewer symptoms and toxicities were associated with the second- and third-generation tkis compared with crizotinib. In multivariable analysis, only stable disease state and baseline Eastern Cooperative Oncology Group performance status were associated with improved hus. Conclusions: There was no significant decrease in hus when patients with ALK+ disease were treated longitudinally with each tki, as long as patients were clinically stable. Alectinib, brigatinib, and lorlatinib had the best toxicity profiles and exhibited high mean hus longitudinally in the real-world setting. [ABSTRACT FROM AUTHOR]

Background Accurate classification of lung cancer subtypes has become critical in tailoring lung cancer treatment. Our study aimed to evaluate changes in diagnostic testing and pathologic subtyping of advanced non-small-cell lung cancer (nsclc) over time at a major cancer centre. Methods In a review of patients diagnosed with advanced nsclc at Princess Margaret Cancer Centre between 2007-2009 and 2013-2015, diagnostic method, sample type and site, pathologic subtype, and use of immunohistochemistry (ihc) staining and molecular testing were abstracted. Results The review identified 238 patients in 2007-2009 and 283 patients in 2013-2015. Over time, the proportion of patients diagnosed with adenocarcinoma increased to 73.1% from 60.9%, and diagnoses of nsclc not otherwise specified (nos) decreased to 6.4% from 18.9%, p < 0.0001. Use of diagnostic bronchoscopy decreased (26.9% vs. 18.4%), and mediastinal sampling procedures, including endobronchial ultrasonography, increased (9.2% vs. 20.5%, p = 0.0001). Use of ihc increased over time to 76.3% from 41.6% (p < 0.0001). Larger surgical or core biopsy samples and those for which ihc was performed were more likely to undergo biomarker testing (both p < 0.01). Conclusions Customizing treatment based on pathologic subtype and molecular genotype has become key in treating patients with advanced lung cancer. Greater accuracy of pathology diagnosis is being achieved, including through the routine use of ihc. [ABSTRACT FROM AUTHOR]

Background Multiple clinical trials for the treatment of advanced EGFR-mutated non-small-cell lung cancer (nsclc) have recently been reported. As a result, the treatment algorithm has changed, and many important clinical questions have been raised:■What is the optimal first-line treatment for patients with EGFR-mutated nsclc? ■What is preferred first-line treatment for patients with brain metastasis? ■What is the preferred second-line treatment for patients who received first-line first- or second-generation tyrosine kinase inhibitors (tkis)? ■What is the preferred treatment after osimertinib? &9632; What evidence do we have for treating patients whose tumours harbour uncommon EGFR mutations? Methods A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on practice recommendations for the treatment of advanced EGFR-mutated nsclc. Results The published overall survival results for osimertinib, combined with its central nervous system activity, have led to osimertinib becoming the preferred first-line treatment for patients with common EGFR mutations, including those with brain metastasis. Other agents could still have a role, especially when osimertinib is not available or not tolerated. Treatment in subsequent lines of therapy depends on the first-line therapy or on T790M mutation status. Treatment recommendations for patients whose tumours harbour uncommon EGFR mutations are guided mainly by retrospective and limited prospective evidence. Finally, the evidence for sequencing and combining tkis with chemotherapy, angiogenesis inhibitors, checkpoint inhibitors, and other new therapeutics is reviewed. Conclusions This Canadian expert consensus statement and algorithm were driven by significant advances in the treatment of EGFR-mutated nsclc. [ABSTRACT FROM AUTHOR]

Introduction Improving health-related quality of life (hrqol) is a key goal of systemic therapy in advanced lung cancer, although routine assessment remains challenging. We analyzed the impact of a real-time electronic hrqol tool, the electronic Lung Cancer Symptom Scale (elcss-ql), on palliative care (pc) referral rates, patterns of chemotherapy treatment, and use of other supportive interventions in patients with advanced non-small-cell lung cancer (nsclc) receiving first-line chemotherapy. Methods Patients with advanced nsclc starting first-line chemotherapy were randomized to their oncologist receiving or not receiving their elcss-ql data before each clinic visit. Patients completed the elcss-ql at baseline, before each chemotherapy cycle, and at subsequent follow-up visits until disease progression. Prospective data about the pc referral rate, hrqol, and use of other supportive interventions were collected. Results For the 95 patients with advanced nsclc who participated, oncologists received real-time elcss-ql data for 44 (elcss-ql arm) and standard clinical assessment alone for 51 (standard arm). The primary endpoint, the pc referral rate, was numerically higher, but statistically similar, for patients in the elcss-ql and standard arms. The hrqol scores over time were not significantly different between the two study arms. Conclusions The elcss-ql is feasible as a tool for use in routine clinical practice, although no statistically significant effect of its use was demonstrated in our study. Improving access to supportive care through the collection of patient-reported outcomes and hrqol should be an important component of care for patients with advanced lung cancer. [ABSTRACT FROM AUTHOR]

Cancer treatment and management have become increasingly economically burdensome. Consequently, to help with planning health service delivery, it is vital to understand the associated costs. Administrative databases can be used to help understand and generate real-world system-level costs. Using databases to generate costs can take one of two approaches: top-down or bottom-up. Top-down approaches disaggregate the total health care spending from a global health care budget by sector and provider. A bottom-up approach begins with individual-level health care use and its costs, which are then aggregated. [ABSTRACT FROM AUTHOR]

Most small cell lung cancer cases present as Stage IV (M1) or extensive stage (ES-SCLC), which are defined as tumor extending outside the hemithorax without a tolerable radiation portal. The CREST trial demonstrated improved local control with a modest overall survival (OS) benefit at the 2-year secondary endpoint of 14% survival with consolidative thoracic radiotherapy (CTRT) compared to 3% without CTRT. Low toxicity rates were also observed. This study reports our institutional ES-SCLC experience for patients treated with CTRT. A retrospective review was conducted on ES-SCLC patients treated with CTRT at our institution between 2014 and 2019. CTRT was defined as ≥30 Gy of thoracic radiotherapy. OS and tolerability of treatment were assessed in this population. Chemotherapy details were also captured. OS rate was determined using the Kaplan-Meier method and the time from start of CTRT to last date of follow-up or death. CTRT tolerability was determined using incidence and grade of esophagitis and radiation pneumonitis as per CTCAE v5. We identified 100 ES-SCLC patients treated with any thoracic RT at our institute, of which 45 received thoracic RT for palliative intent or with <30 Gy. The remaining 55 patients received ≥30 Gy CTRT and were included for analysis. The median age was 65.1 years (range 46.6-86.9) and 36 (65%) were male. The median follow-up for this sample was 0.8 (range 0.03-4.2) years. Median chemotherapy cycles were 6 (range 1-6), most receiving ≥4 cycles (87%) and completing chemotherapy prior to CTRT initiation (91%) with a minority concurrently receiving chemotherapy and CTRT (9%). Platinum chemotherapy was the most common (96%) with 2 patients receiving etoposide alone (4%). The most common CTRT regimens were 30 Gy in 10 fractions (80%) followed by 40 Gy in 15 fractions (9%) and 45 Gy in 30 twice-daily fractions (7%). Most patients (67%) were treated with IMRT/VMAT technique, while the remaining (33%) patients were treated with 3DCRT. The median survival time was 1.3 years with 1- and 2-year OS of 57.2% (CI 44.0 – 74.3%) and 26.1% (CI 12.9 – 52.7%), respectively. CTRT was well tolerated with no grade 4+ toxicities. The most common toxicity was esophagitis with 21 patients (39%), of which 15 were G1 (28%) and 6 were G2 (11%). Radiation pneumonitis was present in 5 patients (9.2%) with 1 G1 (2%), 3 G2 (6%), and 1 G3 (2%) cases. Consolidative TRT for ES-SCLC in this institutional series was at least as good as the reported CREST outcome with modest acute toxicities in this cohort. Disease burden at diagnosis, chemotherapy response, patterns of failure, and subsequent therapies will be further investigated. [ABSTRACT FROM AUTHOR]

The ROS1 kinase is an oncogenic driver in non-small-cell lung cancer (NSCLC). Fusion events involving the ROS1 gene are found in 1%–2% of NSCLC patients and lead to deregulation of a tyrosine kinase–mediated multi-use intracellular signalling pathway, which then promotes the growth, proliferation, and progression of tumour cells. ROS1 fusion is a distinct molecular subtype of NSCLC, found independently of other recognized driver mutations, and it is predominantly identified in younger patients (<50 years of age), women, never-smokers, and patients with adenocarcinoma histology. Targeted inhibition of the aberrant ROS1 kinase with crizotinib is associated with increased progression-free survival (PFS) and improved quality-of-life measures. As the sole approved treatment for ROS1-rearranged NSCLC, crizotinib has been demonstrated, through a variety of clinical trials and retrospective analyses, to be a safe, effective, well-tolerated, and appropriate treatment for patients having the ROS1 rearrangement. Canadian physicians endorse current guidelines which recommend that all patients with nonsquamous advanced NSCLC, regardless of clinical characteristics, be tested for ROS1 rearrangement. Future integration of multigene testing panels into the standard of care could allow for efficient and cost-effective comprehensive testing of all patients with advanced NSCLC. If a ROS1 rearrangement is found, treatment with crizotinib, preferably in the first-line setting, constitutes the standard of care, with other treatment options being investigated, as appropriate, should resistance to crizotinib develop. [ABSTRACT FROM AUTHOR]

Background Economic evaluations are an integral component of many clinical trials. Costs used in those analyses are based on the prices of branded drugs when they first enter the market. The effect of genericization on the costeffectiveness (ce) or cost-utility (cu) of an intervention is unknown because economic analyses are rarely updated using the costs of generic drugs. Methods We re-examined the ce or cu of regimens previously evaluated in Canadian Cancer Trials Group (cctg) studies that included prospective economic evaluations and where genericization has occurred or is anticipated in Canada. We incorporated the new costs of generic drugs to characterize changes in ce or cu. We also determined acceptable cost levels of generic drugs that would make regimens reimbursable in a publicly funded health care system. Results The four randomized controlled trials included (representing 1979 patients) were cctg br.10 (early lung cancer, adjuvant vinorelbine-cisplatin vs. observation, n = 172), cctg br.21 (metastatic lung cancer, erlotinib vs. placebo, n = 731), cctg co.17 (metastatic colon cancer, cetuximab vs. best supportive care, n = 557), and cctg ly.12 (relapsed or refractory lymphoma, gemcitabine-dexamethasone-cisplatin vs. cytarabine-dexamethasone-cisplatin, n = 619). Since the initial publication of those trials, the genericization of vinorelbine, erlotinib, cetuximab, and cisplatin has taken place or is expected in Canada. Costs of generics improved the ces and cus of treatment significantly. For example, genericization of erlotinib ($1460.25 per 30 days) resulted in an incremental cost-effectiveness ratio (icer) of $45,746 per life-year gained compared with $94,638 for branded erlotinib. Likewise, genericization of cetuximab ($275.80 per 100 mg) produced an icer of $261,126 per quality-adjusted life-year (qaly) gained compared with $299,613 for branded cetuximab. Decreases in the cost of generic cetuximab to $129.39 and $63.51 would further improve the icer to $150,000 and $100,000 per QALY respectively. Conclusions Genericization of a costly oncology drug can modify the ce and cu of a regimen significantly. Failure to revisit economic analyses with the costs of generics could be a missed opportunity for funding bodies to optimize value-based allocation of health care resources. At current levels, the costs of generics might not be sufficiently low to sustain publicly funded health care systems. [ABSTRACT FROM AUTHOR]

Background Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (NSCLC) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment. Methods An expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions. Results Treatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified. Conclusions In each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged. [ABSTRACT FROM AUTHOR]

Background Afatinib, an irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), is approved for first-line therapy in advanced EGFR mutation--positive non-small-cell lung cancer (NSCLC) and has previously demonstrated activity after failure of chemotherapy and reversible EGFR TKIS, with improved response and progression-free survival, compared with placebo. Outcomes in pretreated patients with advanced NSCLC receiving afatinib through a Canadian special access program (SAP) are reported here. Methods Patients with NSCLC progressing after at least 1 line of chemotherapy and an EGFR TKI were eligible to enrol in the SAP. Characteristics of patients from the two largest accruing Canadian centres were retrospectively reviewed, including demographics, disease and treatment data, and patient outcomes. Results The 53 patients who received afatinib (57% women, 51% never-smokers, 26% of East Asian ethnicity, and 66% with adenocarcinoma) had a median age of 59 years. EGFR mutations were documented in 25%, and EGFR wildtype in 8%. All patients had received prior EGFR TKI treatment, with 42% achieving a response. Patients took afatinib for a median of 2 months (range: 0-26 months); 17% required 1 or more dose reductions. Of 47 evaluable patients receiving afatinib, 10 experienced tumour shrinkage, and 11, stable disease. Median survival from afatinib initiation was 5 months (95% confidence interval: 2 months to 8 months). Grade 3 or greater diarrhea, rash, paronychia, and stomatitis were seen in 9%, 11%, 6%, and 4% of patients respectively. Conclusions In an unselected population of pretreated patients with advanced NSCLC after TKI failure, median survival with afatinib therapy was 5 months. Through a SAP, afatinib demonstrated activity in clinical practice, with manageable toxicity. [ABSTRACT FROM AUTHOR]

Purpose Advances in personalized medicine have produced novel tests and treatment options for women with breast cancer. Relatively little is known about the process by which such tests are adopted into oncology practice. The objectives of the present study were to understand the experiences of medical oncologists with multigene expression profile (GEP) tests, including their adoption into practice in early-stage breast cancer, and the perceptions of the oncologists about the influence of test results on treatment decision-making. Methods We conducted a qualitative descriptive study involving interviews with medical oncologists from academic and community cancer centres or hospitals in 8 communities in Ontario. A 21-gene breast cancer assay was used as the example of GEP testing. Qualitative analytic techniques were used to identify the main themes. Results Of 28 oncologists who were approached, 21 (75%) participated in the study [median age: 43 years; 12 women (57%)]. Awareness and knowledge of GEP testing were derived from several sources: international scientific meetings, participation in clinical studies, discussions with respected colleagues, and manufacturer-sponsored meetings. Oncologists observed that incorporating GEP testing into their clinical practice resulted in several changes, including longer consultation times, second visits, and taking steps to minimize treatment delays. Oncologists expressed divergent opinions about the strength of evidence and added value of GEP testing in guiding treatment decisions. Conclusions Incorporation of GEP testing into clinical practice in early-stage breast cancer required oncologists to make changes to their usual routines. The opinions of oncologists about the quality of evidence underpinning the test affected how much weight they gave to test results in treatment decision-making. [ABSTRACT FROM AUTHOR]

Background Although molecular testing has become standard in managing advanced nonsquamous non-small-cell lung cancer (NSCLC), most patients undergo minimally invasive procedures, and the diagnostic tumour specimens available for testing are usually limited. A knowledge translation initiative to educate diagnostic specialists about sampling techniques and laboratory processes was undertaken to improve the uptake and application of molecular testing in advanced lung cancer. Methods A multidisciplinary panel of physician experts including pathologists, respirologists, interventional thoracic radiologists, thoracic surgeons, medical oncologists, and radiation oncologists developed a specialty-specific education program, adapting international clinical guidelines to the local Ontario context. Expert recommendations from the program are reported here. Results Panel experts agreed that specialists procuring samples for lung cancer diagnosis should choose biopsy techniques that maximize tumour cellularity, and that conservation strategies to maximize tissue for molecular testing should be used in tissue processing. The timeliness of molecular reporting can be improved by pathologist-initiated reflex testing upon confirmation of nonsquamous NSCLC and by prompt transportation of specimens to designated molecular diagnostic centres. To coordinate timely molecular testing and optimal treatment, collaboration and communication between all clinicians involved in diagnosing patients with advanced lung cancer are mandatory. Conclusions Knowledge transfer to diagnostic lung cancer specialists could potentially improve molecular testing and treatment for advanced lung cancer patients. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab improved survival as first- and second-line therapy compared with chemotherapy in patients with highly programmed death ligand 1 (PD-L1) expressing advanced non-small cell lung cancer (NSCLC). We report the long-term safety and clinical activity of pembrolizumab as first-line therapy for patients with advanced NSCLC and the correlation between PD-L1 expression and efficacy. Patients and methods: In the open-label phase 1b KEYNOTE-001 trial, treatment-naive patients with advanced NSCLC whose tumors expressed PD-L1 (=1% staining, assessed using a prototype assay) were randomly assigned to intravenous pembrolizumab 2 or 10 mg/kg every 3 (Q3W) or 2 (Q2W) weeks. Response was assessed per central RECIST v1.1 every 9 weeks in all patients who received =1 pembrolizumab dose. Using pre-treatment tumor tissue, a clinical assay quantified the percentage of tumor cells expressing PD-L1 as tumor proportion score (TPS). Results: Between 1 March 2013 and 18 September 2015, 101 patients received pembrolizumab 2 mg/kg Q3W (n = 6), 10 mg/kg Q3W (n = 49), or 10 mg/kg Q2W (n = 46). Of these, 27 (26.7%) had TPS =50%, 52 (51.5%) had TPS 1%-49%, and 12 (11.9%) had TPS <1%. The objective response rate (ORR) was 27% (27/101, 95% CI 18-37) and median overall survival was 22.1 months (95% CI 17.1-27.2). In patients with PD-L1 TPS =50%, ORR, 12-month PFS, and 12-month OS were higher [14/27 (51.9%; 95% CI 32%-71%), 54%, and 85%, respectively] than the overall population [27/101 (26.7%; 95% CI 18.4%-36.5%), 35%, 71%]. Pembrolizumab was well tolerated, with only 12 (11.9%) patients experiencing grade 3/4 treatment-related adverse events and no treatment-related deaths. Conclusions: Pembrolizumab provides promising long-term OS benefit with a manageable safety profile for PD-L1-expressing treatment-naive advanced NSCLC, with greatest efficacy observed in patients with TPS = 50%. [ABSTRACT FROM AUTHOR]

Background: Early palliative care improves the quality of life (QoL) and satisfaction with care of patients with advanced cancer, but little is known about its effect on caregivers. Here, we report outcomes of caregiver satisfaction with care and QoL from a trial of early palliative care. Patients and methods: Twenty-four medical oncology clinics were cluster-randomised, stratified by tumour site (lung, gastrointestinal, genitourinary, breast and gynaecological), to early palliative care team referral, or to standard oncology care with palliative care only as needed. Caregivers of patients with advanced cancer (clinical prognosis of 6-24 months, Eastern Cooperative Oncology Group 0-2) in both trial arms completed validated measures assessing satisfaction with care (FAMCARE-19) and QoL [SF-36v2 Health Survey; Caregiver QoL-Cancer (CQoL-C)], at baseline and monthly for 4 months. We used a multilevel linear random-intercept mixed-effect model to test whether there was improvement in the intervention group relative to the control group over 3 and 4 months. Results: A total of 182 caregivers completed baseline measures (94 intervention, 88 control); 151 caregivers (77 intervention, 74 control) completed at least one follow-up assessment. Satisfaction with care improved in the palliative intervention group compared with controls over 3 months (P=0.007) and 4 months (P=0.02). There was no significant improvement in the intervention group compared with controls for CQoL-C (3 months: P=0.92, 4 months: P=0.51), Physical Component Summary of the SF-36v2 Health Survey (3 months: P=0.83, 4 months: P=0.20), or Mental Component Summary of the SF-36v2 Health Survey (3 months: P=0.87, 4 months: P=0.60). Conclusion: Early palliative care increased satisfaction with care in caregivers of patients with advanced cancer. [ABSTRACT FROM AUTHOR]

Background Despite its importance for patient outcomes, biomarker testing for lung cancer is not uniformly integrated into the Canadian health care system. To better understand current practice patterns for lung cancer biomarker testing, we assessed physician perspectives by specialty and region. Methods A national survey of Canadian lung cancer specialists was conducted to understand their perspectives on biomarker testing in lung cancer. The 11-item survey assessed the current practice and challenges of testing. The survey was sent to 375 specialists. Results The overall response rate for the survey was 36%. Nearly all specialists reported that knowing tumour genotyping results affects patient outcome and influences the treatment decision. Medical oncologists most commonly initiated molecular testing; however, most respondents suggested a shared model involving medical oncologists and pathologists. More than half of all responding specialists had the perception that fewer than 25% of test results are available for first-line treatment decisions. Identified barriers to routine testing for all lung cancer patients included cost, lack of funding, tissue availability, and sample quality. Conclusions There was clear agreement that biomarker testing is important in determining appropriate treatment for patients. There is a need for general consensus on who should initiate molecular testing. Clear clinical guidance for pathologists has to be established for molecular testing, including defining the population to be tested, the timing of testing, and the tests to be performed. Testing could be facilitated by including more information on diagnostic sample requisitions, such as clinical suspicion of primary lung cancer, cancer history, and other samples already collected. [ABSTRACT FROM AUTHOR]

Background Cost avoidance occurs when, because of provision of a drug therapy [drug cost avoidance (DCA)] or a pathology test [pathology cost avoidance (PCA)] during trial participation, health care payers need not pay for standard treatments or testing. The aim of our study was to estimate the total DCA and PCA for Canadian patients enrolled in relevant phase iii trials conducted by the NCIC Clinical Trials Group. Methods Phase iii trials that had completed accrual and resulted in DCA or PCA were identified. The PCA was calculated based on the number of patients screened and the test cost. The DCA was estimated based on patients randomized, the protocol dosing regimen, drug cost, median dose intensity, and median duration of therapy. Costs are presented in Canadian dollars. No adjustment was made for inflation. Results From 1999 to 2011, 4 trials (1479 patients) resulted in PCA and 17 trials (3195 patients) resulted in DCA. The total PCA was estimated at $4,194,849, which included testing for KRAS ($141,058), microsatellite instability ($18,600), and 21-gene recurrence score ($4,035,191). The total DCA was estimated at $27,952,512, of which targeted therapy constituted 43% (five trials). The combined PCA and DCA was $32,147,361. Conclusions Over the study period, trials conducted by the NCIC Clinical Trials Group resulted in total cost avoidance (PCA and DCA) of approximately $7,518 per patient. Although not all trials lead to cost avoidance, such savings should be taken account when the financial impact of conducting clinical research is being considered. [ABSTRACT FROM AUTHOR]

Objective Administrative data are used to describe the pancreatic cancer (PCC) population. The analysis examines demographic details, incidence, site, survival, and factors influencing mortality in a cohort of individuals diagnosed with PCC. Methods Incident cases of PCC diagnosed in Ontario between 1 January 2004 and 31 December 2011 were extracted from the Ontario Cancer Registry. They were linked by encrypted health card number to several administrative databases to obtain demographic and mortality information. Descriptive, bivariate, and survival analyses were conducted. Results During the period of interest, 9221 new cases of PCC (4548 in men, 4673 in women) were diagnosed, for an age-adjusted standardized annual incidence in the range of 8.6-9.5 per 100,000 population. Mean age at diagnosis was 70.3 ± 12.5 years (standard deviation). Five-year survival was 7.2% (12.8% for those <60 years of age and 3.6% for those >80 years of age). Survival varied by sex, older age, rural residence, lower income, site of involvement in the pancreas, and presence of comorbidity. Conclusions The mortality rate in PCC is exceptionally high. With an increasing incidence and a mortality positively associated with age, additional support will be needed for this highly fatal disease as demographics in Ontario continue to trend toward a higher proportion of older individuals. [ABSTRACT FROM AUTHOR]

Background Patient function is a key part of the clinical decision to offer chemotherapy and has, in earlier studies, been associated with chemotherapy toxicity. Objective testing might be more accurate than patient-reported or physician-assessed physical function, and thus might be a stronger predictor of chemotherapy toxicity in older adults. Methods Patients, 70 years of age and older, with thoracic or colorectal cancer were recruited. Three physical tests were performed before commencement of a new line of chemotherapy: grip strength, 4-m walk test, and the Timed Up and Go (TUG). Our pilot study explored the association between those tests and chemotherapy toxicity. Results The 24 patients recruited had a median age of 74.5 years (range: 70-84 years), and 54.2% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Median score on the Charlson comorbidity index was 1 (range: 0-4). Almost two thirds had metastatic disease, 70% were chemonaïve, and 83.3% were about to receive polychemotherapy. Patients had a mean tug of 13.2 ± 5.7 s and a mean gait speed of 0.74 ± 0.24 m/s; 50% had a grip strength test in the lowest 20th percentile. Grades 3-5 chemotherapy toxicities occurred in 34.7% of the patients; two thirds required a dose reduction or delay; and one third discontinued chemotherapy because of toxicity. Hospitalization attributable to chemotherapy was uncommon (12.5%). A trend toward increased severe chemotherapy toxicity with slower gait speed was observed (p = 0.049). Conclusions Abnormalities in objective markers of physical function are common in older adults with cancer, even in those deemed it for chemotherapy. However, those abnormalities were not associated with an increased likelihood of chemotherapy toxicity in the population included in this small pilot study. [ABSTRACT FROM AUTHOR]