On September 25, 2024, the Food and Drug Administration sanctioned osimertinib (Tagrisso, AstraZeneca Pharmaceuticals) for adult patients with locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC) whose condition has remained stable during or after concurrent or sequential platinum-based chemoradiation therapy and whose tumors exhibit EGFR exon 19 deletions or exon 21 L858R mutations, as identified by an FDA-approved assay.
Efficacy and Safety
The efficacy was assessed in LAURA (NCT03521154), a double-blind, randomized, placebo-controlled trial involving 216 adult patients with locally advanced, unresectable stage III NSCLC characterized by EGFR exon 19 deletions or exon 21 L858R mutations who had not experienced progression during or after definitive platinum-based chemoradiation within 42 days preceding study randomization. Patients were randomized in a 2:1 ratio to receive either osimertinib 80 mg orally once daily or a placebo until disease progression or intolerable toxicity occurred.
The primary effectiveness endpoint was progression-free survival (PFS) evaluated by blinded independent central review. Supplementary efficacy outcome measures encompassed overall survival (OS). Osimertinib exhibited a statistically significant enhancement in progression-free survival (PFS) relative to placebo, with a hazard ratio of 0.16 (95% CI: 0.10, 0.24; p-value <0.001). The median progression-free survival (PFS) was 39.1 months (95% confidence interval [CI]: 31.5, not estimable [NE]) in the osimertinib group and 5.6 months (95% CI: 3.7, 7.4) in the placebo group.
Although overall survival data were preliminary in this investigation, with only 36% of the pre-specified fatalities reported for the final analysis, no indication of harm was detected.
The prevalent side events, including laboratory abnormalities (≥20%), were lymphopenia, leukopenia, interstitial lung disease/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal discomfort, cough, and COVID-19 infection.
The advised dosage of osimertinib is 80 mg administered once daily, with or without food, until disease progression or intolerable toxicity occurs.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
