Real-World Pattern of Treatment and Clinical Outcomes of EGFR-Mutant Non-Small Cell Lung Cancer in a Single Academic Centre in Quebec

The discovery of EGFR tyrosine kinase inhibitors (TKI) for the treatment of EGFR mutant (EGFRm) metastatic NSCLC is regarded as a landmark in lung cancer. EGFR-TKIs have now become a standard first-line treatment for EGFRm NSCLC. The aim of this retrospective cohort study is to describe real-world patterns of treatment and treatment outcomes in patients with EGFRm metastatic NSCLC who received EGFR-TKI therapy outside of clinical trials. One hundred and seventy EGFRm metastatic NSCLC patients were diagnosed and initiated on first-line TKI therapy between 2004 and 2018 at the Peter Brojde Lung Cancer Centre in Montreal. Following progression of the disease, 137 (80%) patients discontinued first-line treatment. Moreover, 80/137 (58%) patients received second-line treatment, which included: EGFR-TKIs, platinum-based, or single-agent chemotherapy. At the time of progression on first-line treatment, 73 patients were tested for the T790M mutation. Moreover, 30/73 (41%) patients were found to be positive for the T790M mutation; 62/80 patients progressed to second-line treatment and 20/62 were started on third-line treatment. The median duration of treatment was 11.5 (95% CI; 9.62–13.44) months for first-line treatment, and 4.4 (95% CI: 1.47–7.39) months for second-line treatment. Median OS from the time of diagnosis of metastatic disease was 23.5 months (95% CI: 16.9–30.1) and median OS from the initiation of EGFR-TKI was 20.6 months (95% CI: 13.5–27.6). We identified that ECOG PS ≤ 2, presence of exon 19 deletion mutation, and absence of brain metastases were associated with better OS. A significant OS benefit was observed in patients treated with osimertinib in second-line treatment compared to those who never received osimertinib. Overall, our retrospective observational study suggests that treatment outcomes in EGFRm NSCLC in real-world practice, such as OS and PFS, reflect the result of RCTs. However, given the few observational studies on real-world treatment patterns of EGFR-mutant NSCLC, this study is important for understanding the potential impact of EGFR-TKIs on survival outside of clinical trials. Further real-world studies are needed to characterize patient outcomes for emerging therapies, including first-line osimertinib use and combination of osimertinib with chemotherapy and potential future combination of osimertinib and novel anticancer drug, outside of a clinical trial setting.     

Epidermal growth factor receptor mutations detected by denaturing high‐performance liquid chromatography in nonsmall cell lung cancer

BACKGROUND:

Somatic mutations in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to EGFR‐tyrosine kinase inhibitors (EGFR‐TKI) in patients with nonsmall cell lung cancer (NSCLC).

METHODS:

The authors tested the possibility that nucleotide sequencing may be poorly suited for detection of mutations in tumor samples and found that denaturing high‐performance liquid chromatography (dHPLC) was an efficient and more sensitive method for screening.

RESULTS:

These results suggested that some reports based on standard DNA sequencing techniques may have underestimated mutation rates. In the present report, the authors examined the relationship between the presence and type of EGFR mutations detected by dHPLC and various clinicopathologic features of NSCLC, including response to therapy with EGFR‐TKI. Among 251 patients with advanced disease, 100 individuals received EGFR‐TKI. Those whose tumors harbored a detectable EGFR kinase mutation were much more likely to have a partial response (PR) or stable disease (SD) with EGFR‐TKI therapy than patients whose tumor contained no mutation (80% vs 35%; P = .001). Among the individual genotype subgroups, the frequency of a PR or SD was significantly different between patients with an exon 19 deletion compared with those with no detectable mutation (86% vs 35%; P < .001). Furthermore, patients whose tumors expressed an exon 19 mutant EGFR isoform exhibited a trend toward better EGFR‐TKI response (86% vs 67%; P = .171) and improved survival compared with patients whose tumors expressed an exon 21 mutation.

CONCLUSIONS:

Our findings warrant confirmation in large prospective trials and exploration of the biological mechanisms of the differences between mutation types. Cancer 2010. © 2010 American Cancer Society.     

Montreal prognostic score: estimating survival of patients with non-small cell lung cancer using clinical biomarkers

Background:

For evidence-based medical practice, well-defined risk scoring systems are essential to identify patients with a poor prognosis. The objective of this study was to develop a prognostic score, the Montreal prognostic score (MPS), to improve prognostication of patients with incurable non-small cell lung cancer (NSCLC) in everyday practice.

Methods:

A training cohort (TC) and a confirmatory cohort (CC) of newly diagnosed patients with NSCLC planning to receive chemotherapy were used to develop the MPS. Stage and clinically available biomarkers were entered into a Cox model and risk weights were estimated. C-statistics were used to test the accuracy.

Results:

The TC consisted of 258 patients and the CC consisted of 433 patients. Montreal prognostic score classified patients into three distinct groups with median survivals of 2.5 months (95% confidence interval (CI): 1.8, 4.2), 8.2 months (95% CI: 7.0, 9.4) and 18.2 months (95% CI: 14.0, 27.5), respectively (log-rank, P<0.001). Overall, the C-statistics were 0.691 (95% CI: 0.685, 0.697) for the TC and 0.665 (95% CI: 0.661, 0.670) for the CC.

Conclusion:

The MPS, by classifying patients into three well-defined prognostic groups, provides valuable information, which physicians could use to better inform their patients about treatment options, especially the best timing to involve palliative care teams.     

The Impact of COVID-19 on the Diagnosis and Treatment of Lung Cancer at a Canadian Academic Center: A Retrospective Chart Review

The large burden of COVID-19 on health care systems worldwide has raised concerns among medical oncologists about the impact of COVID-19 on the diagnosis and treatment of lung cancer patients. In this retrospective cohort study, we investigated the impact of COVID-19 on lung cancer diagnosis and treatment before and during the COVID-19 era. New lung cancer diagnoses decreased by 34.7% during the pandemic with slightly more advanced stages of disease, there was a significant increase in the utilization of radiosurgery as the first definitive treatment, and a decrease in both systemic treatment as well as surgery compared to the pre-COVID-19 era. There was no significant delay in starting chemotherapy and radiation treatment during the pandemic compared to pre-COVID-19 time. However, we observed a delay to lung cancer surgery during the pandemic time. COVID-19 seems to have had a major impact at our lung cancer center on the diagnoses and treatment patterns of lung cancer patients. Many oncologists fear that they will see an increase in newly diagnosed lung cancer patients in the coming year. This study is still ongoing and further data will be collected and analyzed to better understand the total impact of the COVID-19 pandemic on our lung cancer patient population.     

An exploratory comparative analysis of tyrosine kinase inhibitors or docetaxel in second-line treatment of EGFR wild-type non-small-cell lung cancer: a retrospective real-world practice review at a single tertiary care centre

Background

Treatment for advanced non-small-cell lung cancer (nsclc), especially in patients with wild-type EGFR, remains limited. Recently, erlotinib, a tyrosine kinase inhibitor (tki) targeting EGFR mutation, was approved as second-line treatment in EGFR wild-type nsclc. Despite evidence of better overall survival (os) with chemotherapy than with tki in second-line treatment, data on the use of tki in the real-life clinical setting remain limited. The present practice review of tki use for second- and third-line treatment in EGFR wild-type nsclc also compares clinical outcomes for tki and single-agent docetaxel as second-line treatment.

Methods

Our retrospective cohort study included patients with EGFR wild-type nsclc treated at the Jewish General Hospital (Montreal, QC) between 2003 and 2013. Patients received a tki (erlotinib or gefitinib) in the second and third line or docetaxel in the second line. For each group, we determined os, disease control rate, progression-free survival (pfs), and event-free survival (efs).

Results

The tki group included 145 patients, with 92 receiving second-line treatment. In the control group, 53 patients received docetaxel as second-line therapy. In the tki group, os was 6.0 months; pfs, 2.7 months; and efs, 3.0 months. Comparing second-line treatments, os was 5.3 and 5.0 months respectively (p = 0.88), pfs was 2.5 and 1.8 months respectively (p = 0.041), and efs was 3.0 and 1.7 months respectively (p = 0.009).

Conclusions

In our study cohort, second-line therapy for EGFR wild-type nsclc with tki (compared with docetaxel) was associated with statistically better pfs and efs and noninferior os. Those findings raise the question of whether efs should also be considered when choosing second-line treatment in this patient population.     

Prevalence of emotional distress in newly diagnosed lung cancer patients

Goals of work

Distress is defined by the National Comprehensive Cancer Network as a multifactorial unpleasant emotional experience of a psychological, social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer. We investigated the prevalence and associated symptoms of distress in newly diagnosed lung cancer patients.

Patients and methods

Between November 2005 and July 2007, 98 newly diagnosed lung cancer patients completed an assessment. The Distress Thermometer (DT) and Edmonton Symptom Assessment Scale (ESAS) were used as screening tools.

Main results

Fifty (51%) patients reported clinically significant distress (≥4) on the DT. Of those, 26 (52%) patients reported high levels of depression, nervousness, or both on ESAS. The remaining 24 (48%) patients had elevated levels of distress but no significant depression or nervousness. A correlation between the DT and the total ESAS score was observed (Pearson correlation?=?0.46). The ten items of the ESAS together explained 46% of the variability in DT scores. The depression and nervousness ESAS items were significant predictors of DT score (p?<?0.01 for both items). However, once the two psychosocial items, depression and nervousness, were removed from the total ESAS score, leaving only physical symptoms and the sleeplessness item, the predictive power of the model decreased to R²?=?0.12.

Conclusions

The prevalence of distress in lung cancer patients is high. The DT appears to discriminate between physical and emotional distress. This easily measured score may determine which patients require further intervention for emotional distress.     

Screening for depressive symptoms in patients with unresectable lung cancer

Introduction Early identification of psychological distress and depression is important to optimise the quality of life in patients with advanced non-small cell lung cancer (NSCLC). The prevalence of depression may vary, depending on the time since diagnosis of cancer, results of the treatment and the prognosis. The purpose of this study was to compare the efficacy of a self-administered screening tool (Hospital Anxiety and Depression Scale (HADS)) with a health professional administered tool (Montgomery–Asberg Depression Rating Scale (MADRS)) and to explore the variability of major affective symptoms in patients with unresectable lung cancer during the initial 7–8 weeks of chemotherapy treatment for their illness. Material and methods Patients with newly diagnosed unresectable lung cancer were screened on four occasions for anxiety and depressive symptoms simultaneously using the self-rated HADS and the MADRS administered by a psycho-oncologist or a trained research associate. The first assessment was done within 1 week of diagnosis and was repeated on 3 occasions during the initial 2 cycles of chemotherapy. Results Forty-nine patients, aged 38–82 years (median age 63 years) were enrolled. All patients had advanced NSCLC (stages 3A, 3B and 4) and 61% (30 patients) had an ECOG performance status (PS) of 1 or greater. The point prevalence of depression measured by an interviewer using the MADRS at visits 1–4 was 49%, 51%, 47%, and 41%, respectively. The point prevalence of self-reported depression (HADS) was significantly (p < 0.001) lower at each assessment point (18%, 20%, 6%, 12%) compared to health professional detected depression (MADRS). Although MADRS and HADS showed very strong (Pearson’s correlation = 0.8) and significant (p < 0.001) correlation, the concordance rate in identifying the same cases of depression was only 54%. Clinical implication and conclusion The prevalence of depression among advanced lung cancer patients is high and varies very little during the first 2 cycles of chemotherapy. Among a variety of tools available for the screening of depression, a semi-structured interview is more effective at identifying clinically significant depression than a self-administered questionnaire.     

The predictive value of pre-treatment inflammatory markers in advanced non-small-cell lung cancer

Background

Accurate prediction of outcome in advanced non-small-cell lung cancer (nsclc) remains challenging. Even within the same stage and treatment group, survival and response to treatment vary. We set out to determine the predictive value of inflammatory markers C-reactive protein (crp) and white blood cells (wbcs) in patients with advanced nsclc.

Patients and Methods

Patients were assigned a prognostic index (pi):

• 0 for crp 10 mg/L or less and wbcs 11×10⁹/L or less,
• 1 if one of the two markers was elevated, and
• 2 if both markers were elevated.

We then used chest computed tomography (ct) imaging to evaluate response after 2 cycles of chemotherapy treatment.

Results

Of 134 patients, 46 had a pi of 0; 60, a pi of 1; and 28, a pi of 2. Disease progressed in 41 patients. Progression was significantly more frequent among patients with a pi of 2 (p = 0.008). Median survival was 20.0 months for the pi 0 group, 10.4 months for the pi 1 group, and 7.9 months for the pi 2 group (p < 0.001). The pi was the only significant prognostic factor for survival even after adjustment for performance status, smoking, and weight loss (hazard ratio: 1.57; 95% confidence interval: 1.2 to 2.14; p = 0.004).

Conclusions

Inflammatory state correlates significantly with both chemotherapy response and survival in stage iv nsclc. The pi may provide additional guidance for therapeutic decision-making.