Time on Treatment and Survival Outcomes for Patients Treated With First-line Osimertinib vs. Other Tyrosine Kinase Inhibitors, for EGFR Mutation-positive Metastatic Non-small Cell Lung Cancer: Real-world Experience Data.

BACKGROUND/AIM: In this observational study, we analyzed the time on treatment (ToT) and overall survival (OS) of patients with metastatic non-small cell lung cancer (mNSCLC) in a 2.7-million-member public health provider in Israel. PATIENTS AND METHODS: Newly diagnosed patients with mNSCLC who initiated first-line tyrosine kinase inhibitor (TKI) therapy between Jan 2017-Dec 2020 were identified from the National Cancer Registry and Maccabi Healthcare Services database. Outcomes were assessed at a minimum of 23 months of follow-up (cutoff: 30th November 2022). All analyses compared first-line treatment osimertinib vs. standard TKIs (erlotinib, afatanib or gefitinib). RESULTS: A total of 165 patients (59% female, median age 68 years) were identified, including 58% smokers, 95% with adenocarcinomas, 33% with brain metastases, and 62%/15%/23% with 0-1/2-4/unknown performance status (PS). Of these, 77 (47%) were treated with standard TKI drugs and 88 (53%) with osimertinib as first-line treatment. The median duration of follow-up was 33.6 months (95%CI=29.9-37.3) and 58.5 months (95%CI=52.5-64.4) for patients who received osimertinib and standard TKIs, respectively. The median ToT (in months) was significantly (p<0.0001) longer with osimertinib (17.6; 95%CI=13.71-23.9) vs. standard TKIs (9.40; 95%CI=7.17-12.1). The 24-month survival rate was 58.0% among patients who received osimertinib and 50.6% among those who received standard TKI therapy (p=0.18). From second-line treatment initiation, 43.8% of those who received second-line osimertinib and 17.7% of those that received other second-line treatment were still alive at 24 months. CONCLUSION: Compared to standard TKIs, first-line osimertinib treatment was associated with a significantly longer ToT, and a longer OS. Our cohort also included patients with PS 2-4 who would not necessarily be included in clinical trials, allowing analysis of a real-world population.

Real-world outcomes of patients with metastatic endocrine-responsive breast cancer receiving palbociclib-based combinations.

Aim: To describe treatment journey and clinical outcomes after palbociclib initiation in HR+/HER2- breast cancer patients across multiple lines. Materials & methods: Adult patients (n = 559) were identified in a population-based study between January 2018 and June 2020. Results: Median follow-up time was 41.2 months. The starting dose was 125 mg for more than 85% of patients, and a third had dose reduction. Median time on treatment was 30.5 months for palbociclib + aromatase inhibitors for patients that received first-line treatment after metastatic diagnosis, and 12.6 months for palbociclib + fulvestrant across multiple lines, and longer for patients that had a dose reduction during treatment. At 48 months, 59.3 and 27.3% of patients were still alive, respectively. Subsequent lines resulted in median time on treatment of 4.4-7.7 months in both groups. Conclusion: Time on treatment for palbociclib was comparable to data from clinical trials, and follow-up allowed us to examine subsequent treatment after initial treatment failure. Dose reduction was common in the real-world setting and did not adversely affect efficacy.

We used healthcare data from Israel to study the outcomes of adults (mostly women) who had breast cancer that spread (metastatic) and who started treatment with anticancer medications in the form of palbociclib in combination with either aromatase inhibitors (as first treatment after metastatic disease diagnosis) or fulvestrant (after having been treated with a different medication) between January 2018 and June 2020. Patients treated with palbociclib with aromatase inhibitors (52%) were on average 63 years old, and most had medium to high socioeconomic status (63%) and functioned independently (60%). Patients were treated on average for 30.5 months, and just over a third switched to a different treatment after their disease worsened. Four years after starting treatment, 59% of patients were still alive. Patients treated with palbociclib and fulvestrant, after having been treated with a different medication (48%), were on average 66 years old, and 61% had medium to high socioeconomic status and 50% functioned independently. These patients were treated on average for 12.6 months, and over two-thirds switched to a new treatment. Four years after starting this treatment, 27% of patients were still alive. Overall, most patients included in this study started treatment with the recommended dose of palbociclib (125 mg), and a third had to change to a lower dose to continue treatment (probably due to side effects). Clinical trial registration: NCT04671615 (ClinicalTrials.gov).

Real-world study of PD-L1 testing patterns and treatment distribution in patients with metastatic non-small-cell lung cancer in Israel.

Aim: We describe PD-L1 testing patterns and first-line treatment for patients with metastatic non-small-cell lung cancer in a 2.3 million-member state-mandated health service in Israel. Materials & methods: Newly diagnosed stage IV non-small-cell lung cancer patients initiating systemic anticancer treatment from 1 January 2017 until 31 December 2018 were identified from the national cancer registry and Maccabi Healthcare Service database and followed until 30 June 2019. Results: The cohort consisted of 410 patients; 58% males, median age 68 years, 70% current/former smokers, 81% adenocarcinoma, 14% had brain metastases, and Eastern Cooperative Oncology Group performance status was 46/17/37% for 0-1/2-4/unknown, respectively. A total of 80% tested for PD-L1 expression, of which 47% had tumor proportion score (TPS) ≥ 50%. A total of 95% with TPS ≥ 50% and no known tumor aberrations (including EGFR mutations, and translocations in ALK and ROS1) received first-line PD-1/PD-L1-inhibitor monotherapy, and 80% of untested/TPS < 50% received platinum doublets. Conclusion: Fast uptake of testing was observed, and treatment patterns showed high adherence to guidelines.

Lay abstract We describe PD-L1 testing patterns in a cohort of 410 patients with stage IV non-small-cell lung cancer. All patients were newly diagnosed and newly treated in the years 2017 and 2018. In this cohort, 58% were males, average age was 68 years and 70% were current or former smokers. In this, 80% were tested for PD-L1 expression and 95% of those with a tumor score of >50% and no other tumor receptor mutations received first-line PD-1/PD-L1-inhibitor monotherapy (most receiving pembrolizumab). Moreover, 80% of those untested for PD-L1 or with a low tumor proportion score (<50%) received chemotherapy. After introduction in 2017, a fast uptake of PD-L1 testing was observed, and treatment patterns showed high adherence to guidelines.

Real World Analysis of Small Cell Lung Cancer Patients: Prognostic Factors and Treatment Outcomes.

In this observational study, we assessed treatment patterns and prognostic factors in patients with small cell lung cancer (SCLC) in a large state-mandated healthcare organization in Israel. Methods: All incident cases with histologically confirmed SCLC who initiated systemic anti-cancer treatment between 2011 and 2017 were identified. Treatment patterns and overall survival (OS) were evaluated for each line of therapy. Results: A total of 235 patients were identified (61% male, median age 64 years, 95% ever smokers, 64% had extensive stage). The first-line treatment was platinum-etoposide regimen for 98.7% of the cohort. The second and third-line regimen were given to 43% and 12% of patients, respectively. Mean OS for extensive and limited stage patients was 9.1 and 23.5 months respectively. In a multivariable model, increased risk for mortality was observed among patients with an ECOG performance status (PS) of 2 compared to a PS of 0-1 for the extensive stage patients (Hazard ratio (HR) = 1.63, 95% confidence ratios (CI): 1.00-2.65); and for males compared to females for the limited stage patients (HR = 2.17; 95% CI: 1.12-4.20). Regarding all 2nd line patients in a multivariable model incorporating relevant confounding factors, demonstrated a significantly better outcome with platinum-based regimens compared to topotecan. Median survival after initiation of 2nd line in platinum-sensitive patients was longer (p = 0.056) for those re-challenged with platinum-based regimen (n = 7): 6.8mo (6.1-not reported (NR)), compared with those switched to a different treatment (n = 27): 4.5 mo (2.6-6.6) for extensive stage patients, and a non-significant difference was also observed for limited stage patients. Conclusion: To our knowledge, this is one of the largest real-world studies of SCLC patients. OS for SCLC patients was similar to that reported in clinical trials. PS for extensive stage patients and sex for limited stage patients were significant correlates of prognosis. Re-challenge of the platinum-based doublet was associated with longer OS compared to switching treatment in extensive stage patients.

Does high-dose gestational folic acid increase the risk for autism? The birth order hypothesis.

There has been a dramatic increase in the incidence of autism spectrum disorder (ASD) in recent decades but the causes have not been elucidated. To date, numerous studies have shown that the FDA-recommended doses of folic acid (400 mcg/d) render a protective effect against ASD. Yet, a recent prospective study has claimed that while self-reported folic acid supplementation was associated with decreased risk of ASD, very high levels of maternal plasma folate levels (<60.3 nmol/L) were associated with 2.5 time increased risk of ASD. This study has led to high levels of public anxiety because many women use high dose folic acid to prevent neural tube defects. We hypothesize that because ASD children have been documented to be much more likely to be first or second born, and women consume significantly more folic acid during their first and second pregnancies, the claim that high dose folic acid causes ASD is based on a previously unrecognized birth order bias. This article presents evidence for the wrong claim that high dose folic acid causes ASD. The question whether high exposure level of folic acid is associated with increased risk of ASD is not merely a theoretical issue, because many women at increased risk for NTD in their offspring need substantially higher daily doses of folic acid (1 mg, or 5 mg), than the FDA-recommended 400 mcg daily.

Non-adherence with bisphosphonates among patients with osteoporosis: impact on fracture risk and healthcare cost .

Osteoporosis-related fractures at the spine and hip have a substantial impact on mortality, morbidity, and quality of life in older adults worldwide. Adherence to bisphosphonates is essential for effective treatment and fracture prevention. Nevertheless, numerous studies from various populations and study designs clearly indicated that adherence and persistence are poor with more than 50% of patients discontinuing therapy within one year. This is primarily explained by mild adverse effects, dosing regimens, and costs. Studies have also shown that good adherence is associated with reduced osteoporosis-related and non-related healthcare costs as soon as 2 years from therapy initiation. Nonetheless, we found only little improvement in adherence rates over the years. In light of the importance of medication adherence and the limited success of previous programs, other than reducing dosing frequency, new directions should be explored to engage patients and care givers in order to improve adherence and prevent fractures.