Tagrisso (osimertinib)

Osimertinib dose reduction in the first-line setting was not associated with inferior OS, suggesting that appropriate dose modification helps maintain PS. Transition to BSC after progression, rather than initial dose intensity, was associated with poor prognosis.

This report of a patient with the rare p.(Cys797Ala) EGFR acquired mutation highlights the role of molecular modelling and IHC for phosphorylated proteins as tools to functionally characterize variants of unknown significance and help clinical decisions.

Patients with EGFR-mutant LUSC or LUAS had shorter overall survival on first-line osimertinib compared with those with EGFR-mutant LUAD...Combined EGFR and MET inhibition suppressed tumor growth in patient-derived xenograft models of LUSC transformation. Together, these findings highlight Rb pathway inactivation as a promoter of LUSC transformation in EGFR-mutant lung cancer and identify MET signaling as a therapeutic vulnerability that may suppress plasticity in this setting and extend response to targeted therapy.

Furthermore, we introduce a positive correlation between compound selectivity for IMPDH2 and the ability to synergize with Osimertinib: the standard of care for EGFR-mutant non-small cell lung cancer. Overall, our results suggest that specifically blocking IMPDH2 is an effective therapeutic strategy for BM by overcoming the immune suppressive effects that have hindered the clinical development of pan-IMPDH inhibitors in the past. An IMPDH2 specific therapy could be coadministered with primary tumor standard of care treatments to provide a safe and interceptional approach for BM.

Small interfering RNA (siRNA)-mediated knockdown of DAAM1 enhances sensitivity to osimertinib, providing functional support for this causal prediction. Overall, CauFinder enables actionable target nomination and testable hypotheses for intervening in disease-relevant state transitions using observational transcriptomic data.

This paper reported a case of concurrent SCLC transformation and ALK fusion occurring after Osimertinib treatment, suggesting that the two can coexist as dual drug resistance mechanisms. Re-biopsy combined with genetic testing is essential for identifying drug resistance mechanisms and guiding individualized therapy..

In this review, we highlight a case example that illustrates key treatment considerations, including balancing efficacy, toxicity, and patient preferences when selecting the optimal palliative therapy. We discuss key treatment considerations for EGFR PACC mutated NSCLC to inform the use of afatinib (the only approved therapy with an indication that includes two EGFR PACC mutations, G719X and S768I), osimertinib, or combination therapies in the upfront setting; limitations of the available data; and ongoing clinical trials specific to the EGFR PACC mutation subgroup that may further refine our understanding of treatment for patients with these tumors.

After propensity score matching (n=412), these differences persisted for treatment duration (12.9 vs. 6.8 months), CNS-rPFS (24.9 vs. 14.5 months), and OS (25.6 vs. 14.6 months), all P<0.001. In real-world practice, osimertinib is associated with longer first-line treatment duration, improved CNS control, and longer survival compared with gefitinib among EGFR-positive mNSCLC patients with brain metastases.

The patient was then initiated on combination therapy with carboplatin (area under the curve 5), pemetrexed (500 mg/m2), and osimertinib (80 mg), completing six cycles. Although limited to a single case, our findings support the growing interest in combining systemic and local therapies in EGFR-mutant non-small cell lung cancer and offer a potential framework for adapting these strategies to molecularly analogous tumors. Longer-term follow-up and further studies are needed to refine patient selection and optimize treatment intensity.

Osimertinib after definitive CRT had an acceptable and manageable safety/tolerability profile, with no new safety findings, supporting osimertinib as the new standard of care in this setting. LAURA clinical trial registration number: NCT03521154.

We evaluated AXL-mRNA overexpression in CTC fractions of NSCLC patients under osimertinib treatment (Group A, n = 39), (collected in the context of a multicenter Phase II clinical study (ClinicalTrials.gov number: NCT02771314) or immunotherapy (Group B, n = 116) at different time points collected in the context of a prospective, multicenter study (ClinicalTrials.gov number: NCT04490564)...In Group B, AXL-mRNA overexpression in CTC fractions was detected in 8/116 (6.9%) samples before immunotherapy, in 8/71 (11.3%) after three or four cycles, while no AXL transcripts were detected at PD. Our results indicate that AXL-mRNA overexpression in CTC fractions deserve to be further evaluated through larger clinical studies as a potential biomarker for anti-AXL targeted therapies in NSCLC.