the Food and Drug Administration approved osimertinib (Tagrisso, AstraZeneca Pharmaceuticals) for adult patients with locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC) whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

AstraZeneca’s Tagrisso (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy has been approved in the European Union (EU) for the 1st-line treatment of adult patients with advanced epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose tumours have exon 19 deletions or exon 21 (L858R) mutations.

On February 16, 2024, the Food and Drug Administration approved osimertinib (Tagrisso, AstraZeneca Pharmaceuticals LP) with platinum-based chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer (la/mNSCLC) whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

AstraZeneca’s Tagrisso (osimertinib) has been approved in the European Union (EU) for the adjuvant treatment of adult patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumour resection with curative intent. Tagrisso is indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 (L858R) mutations.

Tagrisso (osimertinib) was approved for an indication extension…The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has authorised a licence extension for AstraZeneca’s Tagrisso (osimertinib), allowing it to be used in Great Britain as a monotherapy for the adjuvant treatment after complete tumour resection in adult patients with stage IB-IIIA non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.

AstraZeneca’s Tagrisso (osimertinib) has been approved in China for the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC)...Tagrisso is indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 (L858R) mutations.

AstraZeneca Pharma India has received import and market permission in Form CT-20 (subsequent New Drug Approval) from the Drugs Controller General of India for osimertinib 40mg/80mg film coated tablets (Tagrisso)….Osimertinib 40mg/80mg film coated tablets as monotherapy is now approved for additional indication for the adjuvant treatment after complete tumour resection in patients with non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.

AstraZeneca said Thursday the Ministry of Food and Drug Safety approved Tagrisso (ingredient: osimertinib) as an adjuvant treatment after complete tumor resection in early-stage epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer patients....with either an exon 19 deletion or exon 21 L858R substitutions.

AstraZeneca Canada today announced that Health Canada has approved Tagrisso (osimertinib) for the first-line treatment of patients with locally advanced (not amenable to curative therapies), or metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations (either alone or in combination with other EGFR mutations).

TAGRISSO is a kinase inhibitor indicated...as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

Recommendation 4.2....Patients with resected stage III NSCLC with EGFR exon 19 deletion or exon 21 L858R mutation may be offered adjuvant osimertinib after platinum-based chemotherapy (Type: Evidence based; benefit outweighs harm; Evidence quality: moderate; Strength of recommendation: strong).

Osimertinib is indicated for the adjuvant treatment after complete tumour resection in adult patients with stage IB-IIIA NSCLC whose tumours have EGFR exon 19 deletions or exon 21 L858R substitution mutations [I, A].

Adjuvant osimertinib is recommended for patients with sensitizing EGFR (Ex19del or L858R) mutations...

The NCCN NSCLC Panel recommends osimertinib as a preferred first-line therapy option for patients with metastatic NSCLC who have sensitizing EGFR mutations based on the phase 3 trial and FDA approval….The presence of EGFR exon 19 deletions or exon 21 L858R mutations is predictive of treatment benefit from EGFR tyrosine kinase inhibitor (EGFR TKI) therapy (eg, osimertinib)...

Eligible patients (aged ≥18 years [≥20 in Japan and Taiwan], WHO PS 0/1 with completely resected EGFRm (ex19del/L858R) stage IB, II or IIIA [AJCC/UICC 7th edition] NSCLC; adjuvant chemotherapy allowed) were randomized 1:1 to osimertinib 80 mg once daily or placebo until disease recurrence...Adjuvant osimertinib demonstrated an unprecedented, highly statistically significant and clinically meaningful OS benefit in patients with EGFRm stage IB–IIIA NSCLC after complete tumor resection, with or without adjuvant chemotherapy.

Overall, 682 patients with stage IB-IIIA (American Joint Committee on Cancer/Union for International Cancer Control, seventh edition) EGFR-mutated (exon 19 deletion/L858R) NSCLC were randomly assigned 1:1 (stratified by stage, mutational status, and race) to receive osimertinib 80 mg once-daily or placebo for 3 years....These updated data demonstrate prolonged DFS benefit over placebo, reduced risk of local and distant recurrence, improved CNS DFS, and a consistent safety profile, supporting the efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC.

In the double-blind phase III FLAURA study, 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion: Ex19del or p.Leu858Arg: L858R) advanced NSCLC were randomly assigned at a 1:1 ratio to receive either osimertinib or a comparator EGFR-TKI (gefitinib or erlotinib). The primary end point, median PFS, was significantly prolonged with osimertinib relative to comparator EGFR-TKI [18.9 vs. 10.2 months; hazard ratio (HR) for disease progression or death, 0.46; 95% confidence interval (95% CI), 0.37–0.57; P < 0.001].

ADAURA enrolled adult pts with completely resected stage IB/II/IIIA NSCLC, EGFRm (Ex19del/L858R)...At DCO, stage II-IIIA DFS HR was 0.16 (95% CI: 0.08, 0.31, p<0.0001; maturity 40%); stage I-IIIA DFS HR was 0.18 (95% CI: 0.10, 0.33, p<0.0001; maturity 27%). ADFS benefit with osimertinib vs PBO was observed in all pre-specified subgroups of theChina cohort with sufficient events for analysis.

ADAURA is a phase III, double-blind, placebo-controlled study that randomized (1:1) 682 patients with completely resected non-squamous...NSCLC with EGFR exon 19 deletions (del) or L858R mutations (alone or in combination with other EGFR mutations) to receive 80 mg of osimertinib or placebo for up to 3 years....The benefit with osimertinib was seen consistently across all predefined subgroups: type of EGFR mutation (HR 0.12 in exon 19 del, HR 0.35 in L858R), race (HR 0.22 in Asians, HR 0.17 in non-Asians), disease stage (HR 0.39 in stage IB, HR 0.17 in stage II and HR 0.12 in stage IIIA)...

AstraZeneca’s Tagrisso (osimertinib) has been recommended for marketing authorisation in the European Union for the adjuvant treatment of adult patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumour resection with curative intent. If approved, Tagrisso will be indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 (L858R) mutations.

Thirty adults with confirmed EGFRm (ex19del/L858R) locally advanced/metastatic NSCLC, WHO PS 0/1, with no prior therapy for advanced disease, received osimertinib 80 mg QD, and either cisplatin 75 mg/m2 (n=15) or carboplatin AUC5 (n=15), plus pemetrexed 500 mg/m2 every 3 weeks (Q3W)...Osimertinib plus platinum/pemetrexed chemotherapy was generally well tolerated; no new safety signals were identified.

Eligible pts: ≥18 years (Japan/Taiwan: ≥20), WHO PS 0/1, primary non-squamous stage IB/II/IIIA NSCLC, confirmed EGFRm (ex19del/L858R)...2-year DFS rate was 90% with osimertinib vs 44% with PBO….Adjuvant osimertinib is the 1st targeted agent in a global trial to show a statistically significant and clinically meaningful improvement in DFS in pts with stage IB/II/IIIA EGFRm NSCLC...

In this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group)....The median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P=0.046).

FLAURA was a randomized (1:1), double-blind, international phase III study assessing the efficacy and safety of osimertinib (80 mg once daily) versus comparator first-generation EGFR-TKI (gefitinib 250 mg once daily or erlotinib 150 mg once daily) in patients with previously untreated, EGFRm-positive (Ex19del or L858R) locally advanced or metastatic NSCLC...The PFS superiority of osimertinib was consistent irrespective of the type of EGFR-sensitizing mutation at randomization: Ex19del, HR of 0.43 (95% CI, 0.32–0.56; P < 0.0001); L858R, HR of 0.51...

In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation positive (exon 19 deletion or L858R) advanced NSCLC...The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001)....Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation positive advanced NSCLC...

...These include exon 19 deletions, L858R (exon 21), G719X (exon 18), L861Q (exon 21), S768I (exon 20) and T790M (exon 20). ...

...According to the ARMS or Super-ARMS or NGS test results of tumor tissue or plasma from a certified laboratory approved by Chinese regulatory authorities, the tumor carries at least one of the 4 rare EGFR mutations (G719X/L861Q/S768I/T790M) (single mutation or compound mutation), but not other EGFR mutations (including ex19del/L858R). ...

...Have histologically or cytologically confirmed, advanced or metastatic NSCLC, characterized by either EGFR Exon 19del or Exon 21 L858R mutation by an FDA-approved or other validated test of either ctDNA or tumor tissue in a CLIA certified laboratory or an accredited local laboratory. ...

...o Provision of informed consent prior to any study specific procedures.o Patients (male/female) must be > 18 years of age.o Locally advanced or metastatic EGFR mutant NSCLC, not amenable to curative surgery or radiotherapy with confirmation of the presence of EGFR exon 19 deletion or exon 21 p.L858R.o Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow central analysis.o Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with osimertinib. ...

...Tested and confirmed to be EGFR mutation-positive (including exon 19 deletion and exon 21 L858R); 6. ...

...To evaluate the effectiveness of osimertinib in combination with pemetrexed and platinum-based chemotherapy in terms of 3-year OS in adult patients with advanced NSCLC whose tumours have EGFRm exon 19 deletions or exon 21 (L858R) substitution (Cohort 3)....

...L858R, exon 19 deletions, exon 19 insertions, L861Q, G719X....

...- Documented activating EGFR mutation (Exon 19 deletion, T790M, or L858R) on tumor samples by Clinical Laboratory Clinical Laboratory Improvement Amendments (CLIA)-approved test...

...- Patients with a EGFR deletion or mutation in exon 19, exon 21 (L858R, L861Q) or exon 18 (G719X) and concomitant T790M mutation before treatment confirmed centrally....

...- Participants must have histologically confirmed stage IV NSCLC (per AJCC 7th edition) with either the L858R or exon 19 deletion activating EGFR mutation as identified in a CLIA-approved laboratory from tumor tissue....

...- Epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations (either alone or in combination with other EGFR mutations)...

...- Participants must have histologically confirmed stage IV NSCLC (per AJCC 7th edition) with either the L858R or exon 19 deletion activating EGFR mutation as identified in a CLIA-approved laboratory....

...- Presence of sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q)....

...Presence of the sensitising EGFR-mutation (exon 19 deletion and/or exon 21 L858R) detected by an accredited laboratory....

...Confirmation by the local laboratory that the tumour harbours one of the two common EGFR mutations (Ex19del, L858R), either alone or in combination with other EGFR mutations including de novo EGFR mutation resulting in substitution of threonine with methionine at amino acid position 790 in exon 20 of EGFR (T790M) or uncommon EGFR mutations G719X, S768I, and L861Q, either alone, in combination with each other, or in combination with other uncommon EGFR mutations (excluding all exon 20 insertions) (Uncommon EGFRm Cohort)....

...A tumour which harbours one of the 2 EGFR mutations (Ex19del, L858R) by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test....

...At least one documented uncommon EGFR mutation of G719X/L861Q/S768I/de novo T790M without EGFR Ex19del/L858R/exon 20 insertion as detected in tumour tissue, through real-time PCR or NGS analysis from accredited laboratories approved by the Chinese regulatory authority....

...For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.- Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage II - IIIB N2) disease (according to Version 8 of the IASLC Cancer Staging Manual [IASLC Staging Manual in Thoracic Oncology 2016]).- Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a Mulit-disciplinary Team (MDT) evaluation (which should include a thoracic surgeon, specialised in oncologic procedures).- Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.- A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q).`...

...Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q)....

...Patients with a confirmed EGFR L858R mutation or 19Del before treatment; 2. ...

...• The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19 deletions, L858R), either alone or in combination with other EGFR mutations. ...

...Pathologically confirmed non-small cell lung cancer (NSCLC) with documented EGFR sensitive mutation (EGFR 19del and L858R) positive before Osimertinib 1L....

...EGFR activating mutations include exon19 deletion, T790M, L858R, G719X, L861Q, or S768I....

...The resected lung adenocarcinoma should have actionable EGFR mutation, which is limited to L858R or exon 19 deletion....

...- Patient with common EGFR mutation-positive (exon 19 deletion or L858R mutation, alone or co-occuring with other EGFR mutations)....

...Presence of a common EGFR mutation (Del19 or L858R)....

...The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19 deletions, L858R), either alone or in combination with other EGFR mutations....

...- NSCLC which harbors EGFR exon 19 deletion or L858R mutation....

......

...Patients with EGFR sensitizing mutations (Ex19del or L858R)....

...- Have confirmation of the presence of common EGFR mutations (exon 19 deletion, L858R/exon 21, or G719X) through any locally and internationally accepted standard tests....

...The resected lung adenocarcinoma should have actionable EGFR mutation, which is limited to L858R or exon 19 deletion....

...- The tumor harbors an Ex19del or Ex21-L858R substitution (based on tumor tissue or plasma [ctDNA] assessment)....

......

...As confirmed by the central laboratory, the tumor contains one of the two common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), alone or in conjunction with other EGFR mutations, including T790M; 7....

...History of EGFRm (exon 19 deletion or exon 21 L858R) in the plasma ctDNA by the local testing methods....

...Documented activating EGFR mutation (Exon 19 deletion or L858R) 5....

...Histologically documented that with sensitizing EGFR mutations(either L858R or Exon19del) 7....

...Histologically or cytologically confirmed stage IV or recurrent non-squamous non-small cell lung carcinoma with activating EGFR mutations (exon 19 deletion or exon 21 L858R point mutation) and concurrent TP53 mutations; 6....

...Patients must fulfil one of the following:• Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q)• OR• Must have experienced clinical benefit from EGFR-TKI, according to the Jackman criteri (Jackman et al 2010) followed by systemic objective progression (RECIST or WHO) while on continuous treatment with EGFR TKI7. ...

...The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R)....

...Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q)....

...- Histologically confirmed metastatic or recurrent stage IV NSCLC with activating EGFR mutation other than deletion in exon 19, L858R, T790M and insertion in exon 20...

...EGFR mutation status was confirmed by ARMS fluorescence PCR, including 4 cases of 19del mutant, 4 cases of 21L858R mutant, and 2 cases of wild type; 3. ...

...NGS detection (targeting 150 genes) before treatment using tumor tissues indicating EGFR mutation (exon 19 deletion, or exon 21 L858R) and other concurrent mutations (TP53, Rb1, PTEN, Met, ERBB2, KRAS, BRAF, RET or ROS1); 8. ...

...- Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) 6....

...Patients with EGFR sensitizing mutation (E19Del, L858R, L861Q, G719X) positive, who had shown clinical benefits (responders (CR or PR) and SD ≥6 months) from EGFR-TKIs and had developed progressive disease following those therapy...

...- A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, Exon20 insertions, S7681 and L861Q)....

...Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q)....

...The tumor harbours one of the two common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations, assessed by cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test in a CLIA certified (USA sites) or an accredited local laboratory (sites outside of the USA) or by central testing (cobas® v2 only)....

...- A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (eg., T790M, G719X, Exon20 insertions, S7681 and L861Q)....

...Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q)....

...Group 1: Patient had a documented EGFR Exon 19del or L858R activating mutation and progressed while on osimertinib as first-line therapy in the advanced/metastatic setting....

...- Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR...

...Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q)....

...Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR-TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) or T790M EGFR resistance mutation as assessed by local laboratory/or central laboratory via tissue/cytology or in plasma....

...Confirmation by the central laboratory that the tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including T790M....

...Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including exon 19 deletion and L858R)....

...- Exon 19 deletion, L858R, T790M and uncommon sensitizing EGFR mutations in treatment-naïve patients are allowed....

...Activating EGFR mutation (G719X, exon 19 deletion, L858R, L861Q) detected from circulating tumor DNA either by PANA mutyper® or Cobas® EGFR mutation test....

...The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations known to be associated with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination with other epidermal growth factor receptor (EGFR) mutations, which may include T790M....

...1) Histologically confirmed, treatment naïve EGFR-mutant NSCLC, with or without T790M resistance mutation.2) Presence of sensitising EGFR-mutation (exon 19 deletion and/or exon 21 L858R) detected by an accredited laboratory.3) Synchronous oligo-metastatic stage IV disease (max 5 lesions)4) Measurable disease as defined according to RECIST v1.15) All lesions amenable for radical radiotherapy according to local judgment6) ECOG performance status 0-27) Adequate haematological, renal and liver function 1) CPNM con mutación EGFR sin tratamiento, confirmado histológicamente, con o sin mutación de resistencia T790M.2) Presencia de mutación EGFR sensibilizante (deleción del exón 19 y / o exón 21 L858R) detectada por un laboratorio acreditado.3) Enfermedad sincrónica oligo-metastásica en estadio IV (máximo 5 lesiones)4) Enfermedad medible según se define de acuerdo con RECIST v1.15) Todas las lesiones susceptibles de radioterapia radical según el criterio local.6) estado funcional ECOG 0-27) Función hematológica, renal y hepática adecuada`- Histologically confirmed, treatment naïve EGFR-mutant NSCLC, with or without T790M resistance mutation.- Presence of sensitising EGFR-mutation (exon 19 deletion and/or exon 21 L858R) detected by an accredited laboratory.- Synchronous oligo-metastatic stage IV disease (max 5 lesions).- Measurable disease as defined according to RECIST v1.1.- All lesions amenable for radical radiotherapy according to local judgment.- ECOG performance status 0-2.- Adequate haematological, renal and liver function. ...

...A tumour which harbours one of the 2 EGFR mutations (Ex19del, L858R).9. ...

...- Tumor with an activating mutation of EGF-R (deletion of exon 19 or L858R, L861x, or G719x mutation)...

...Presence of EGFR activating mutations (exon 19 deletion or L858R in exon 21) 6....

...Staging will be according to the pTNM (pathologic tumour,node, metastasis) staging system for lung cancer 8) Confirmation by the local laboratory that the tumour harbours 1 of the following EGFRmutations:-1 of the 2 common EGFR mutations (Ex19del, L858R), either alone or incombination with other EGFR mutations including de novo T790M and excluding allexon 20 insertions (Common EGFRm Cohort); or - Uncommon EGFR mutations G719X, S768I, and L861Q, either alone, in combination with each other, or in combination with other uncommon EGFR mutations (excluding all exon 20 insertions) (Uncommon EGFRm Cohort).9) Complete surgical resection of the primary NSCLC is mandatory. ...

ORBITAL is a multicenter phase II trial investigating the efficacy and safety of osimertinib 80 mg/d in EGFR-mutated NSCLC patients with leptomeningeal metastases (cohort 1) or patients with brain metastases who have not received prior EGFR-Tyrosine kinase inhibitor or radiation therapy (cohort 2)....EGFR mutations were mostly del19 (60.4%) and L858R (30.2%)....Osimertinib demonstrated clinically meaningful responses in patients with EGFR-mutated NSCLC against both leptomeningeal and brain metastases.

PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression....The ORR was 50.9% (95% CI 41.2-60.6) and the DCR was 84.5% (95% CI 76.4-90.7). Median PFS was 7.4 (95% CI 6.0-9.3) months; median OS was 1.63 (95% CI 1.35-2.16) years....Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs.

EGFR mutations included exon 19 del (N=10, 40%) and L858R (N=15, 60%). After 2 cycles of neoadjuvant osimertinib, ORR was 44% (N=11, all partial response) and the remaining 56% (N=14) had stable disease. The MPR rate was 24% (N=6)…In patients with resectable EGFR-mutant NSCLC, neoadjuvant osimertinib is a feasible option that was not associated with surgical delays and induced MPR rate of 24% of resected tumors.

This retrospective multicenter study included patients with mEGFR (ex19/ex21) aNSCLC treated with either osimertinib or the sequence of 1G followed by osimertinib (“sequence group”)... In this real-life study we showed that osimertinib upfront demonstrated prolonged 1L-PFS vs. 1G followed by osimertinib, with better PFSglob in patients with poor-prognosis mEGFR aNSCLC.

...we have evaluated the hypothetical clinical and financial effects of adj osimertinib on the early-stage, EGFRm NSCLC patients at Cleveland Clinic who were treated prior to the FDA approval....82 patients were EGFRm+ (exon 19 deletion or the L858R mutation), and their survival outcomes were used in the SOC arm. At 5 years, 32 (39%) of the patients were alive and disease free. With the addition of adj osimertinib, an estimated average of 61 (71.4%) of patients would have been disease free and alive.

CONTRADICTING EVIDENCE: Both RWDs confirmed poorer prognosis for 1L osimertinib-treated patients with L858R vs ex19del. MDACC cohort showed a 12-mo PFS rate of 63% for L858R (n=45) vs 82% for ex19del (n=60); mPFS was immature….In both RWDs, 1L osimertinib-treated patients with L858R-driven NSCLC had poorer outcomes vs ex19del, consistent with osimertinib’s weaker activity on L858R.

We conducted a phase II study to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC....The most common sensitizing mutations at baseline were deletions in exon 19 (50.9 %) and the L858R point mutation in exon 21 (40.0 %)….Patients received osimertinib, 80 mg/day, every day until disease progression...the overall response rate was 29.1 % (95 % CI, 17.6–42.9), which exceeded the necessary threshold response rate for primary analysis. Stable disease was found in 16 patients (29.1 %)....The median length of PFS was 4.07 months (95 % CI, 2.10–4.30), and the rate of 12-month PFS was 17.3 % (95 % CI, 8.6–28.6).

EGFR mutation-positive NSCLC patients who started EGFR-TKI treatment from September 2018 to August 2020 were enrolled, and first-line osimertinib monotherapy was selected among them....The median progression-free survival (PFS) was 20.0 months (95% CI: 17.6-21.7) and the survival rate at 24 months was 72.4% (95% CI: 68.4-76.0). The PFS by mutation type was 23.5 months (95% CI: 20.9-27.4) for exon 19 deletion and 17.0 months (95% CI: 15.2-19.7) for L858R point mutation in exon 21....Osimertinib showed promising activity with a manageable safety profile in clinical practice, even for patients with poor PS, consistent with effects to previous clinical trials.

Eligible patients with EGFRm (19del or L858R) advanced NSCLC who has received osimertinib monotherapy as first-line therapy were enrolled from 24 sites in China....ORR was 60.0%, DCR was 96.3%. After a median follow-up of 10.2 months, the 1-year PFS rate was 78.8% (95%CI, 66.9-86.8).

This is a multicenter, multinational, retrospective cohort study of Hispanic patients treated with Osimertinib as first-line for EGFR-mutated NSCLC....Identified mutations included EGFR Exon 19 deletions and EGFR pL858R point mutations. Median progression-free survival (PFS) was 14.4 months (95%CI 12.4-18.2 months)….Treatment with first line osimertinib represents an effective and safe option for Hispanic patients with metastatic NSCLC.

We report a single academic center’s experience with real-world osimertinib use in unresectable EGFR-mutated NSCLC...Regarding EGFR mutation, 32 (57%) had exon 19 deletion and 16 (29%) had exon 21 L858R mutation...Median OS for all patients was 32.0 months (95% CI 15.7 – NR) and not reached for the FLAURA-eligible cohort....Outcomes in our real-world FLAURA-eligible patients were better than previously reported.

We retrospectively analyzed patients with advanced and recurrent non-small cell lung cancer who harbored an exon 19 deletion or an exon 21 L858R mutation….The median progression-free survival was 18.8 months and 13.1 months in the osimertinib and afatinib groups, respectively (hazard ratio 0.75 [95% confidence interval 0.48-1.18])....In patients with brain metastasis at baseline, the median progression-free survival was 22.1 months in the osimertinib group, and 10.9 months in the afatinib group (adjusted hazard ratio 0.45 [95% confidence interval 0.21-0.96])...there was a statistical significance revealing that osimertinib provided better median progression-free survival than afatinib in patients with brain metastasis at baseline.

The clinical data of advanced NSCLC patients with BMs who received osimertinib were retrospectively collected....The patients were assigned to one of the two groups according to the therapeutic modality used: the osimertinib monotherapy group or the osimertinib plus RT group....In the L858R mutational subgroup of 31 patients, the osimertinib plus RT group had a longer OS (P = 0.046). In the exon 19 deletion mutational subgroup of 30 patients, OS in the osimertinib alone group was longer than that in the osimertinib plus RT group (P = 0.011).

We assessed the clinical effects of osimertinib as a first-line treatment for patients with poor PS NSCLC with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered osimertinib (80 mg/day) as the initial treatment….The overall objective response rate was 56.3%. The median progression-free survival (PFS) of the entire patient population was 10.5 months and the PS score improved in 8 of 16 patients (50%)....Considering the findings of this study, osimertinib appears to be an effective and safe treatment option for patients with poor PS and advanced NSCLC harboring sensitive EGFR mutations.

We assessed the clinical effects of osimertinib as a first-line treatment for elderly NSCLC patients (≥75 years of age) with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered 80 mg/day osimertinib as initial treatment....The overall objective response rate was 60.5%. The median progression-free survival (PFS) and time to treatment failure (TTF) of the entire patient population were 22.1 months and 14.6 months, respectively.

...combined Osi/Bev versus Osi in pts with NSCLC with EGFR-mt (exon 19 del or L858R) and T790M-mt at progression on prior EGFR TKI...the median PFS was 15.4m (95% CI 9.2-18.0) and 12.3m (6.2-17.2) (PFS events: 64 & 65) in the Osi/Bev and Osi arm respectively (HR 0.96; 0.68- 1.37; p=0.83). Median OS was 24.0m (17.8-32.1) in Osi/Bev and 24.3m (16.9-37.0) in Osi arm (deaths: 46 & 43) (HR 1.03; 0.67-1.56; p=0.91). ORR was 55% in both arms.

As of April 2021, 13 patients with early-stage (6 stage IA/B, 2 Stage IIA/B, and 5 Stage IIIA) EGFR-mutant (7 exon 19 del, 6 L858R) NSCLC have been enrolled and treated with osimertinib for an average of 59 days prior to surgical resection. The mPR rate was 15% (2 of 13). The pathological response rate was 69% (9 of 13).

In this non-interventional, global, multi-center study (NCT04179890), existing medical or electronic health records were identified for consecutive EGFR TKI-naïve patients with EGFRm+ NSCLC (Del19 or L858R) treated in regular clinical practice with first-line afatinib and, following the detection of T790M, second-line osimertinib. ORR with afatinib and osimertinib was 74% and 45%. TTF, OS and ORR were generally consistent across subgroups.

...patients diagnosed with metastatic non-small cell lung cancer (NSCLC) with EGFR mutation...82.2% of this patient population received Osimertinib...EGFR mutation sub-groups, the median OS for patients with EGFR-exon 19-deletion was 26.4 months (95% CI [14.3 – 38.4 months], compared to 36.8 months, 95% CI [34.3 – 39.2 months] for those with EGFR-Exon 21-L858R...

This is an observational, multicenter study enrolling EGFR mut aNSCLC receiving 1L osimertinib...82 pts receiving osimertinib were included in 3 centres...Baseline EGFR mutations were exon 19 deletion in 39 (47.6%) pts, L858R in 36 (43.9%) pts, others in 7 (8.6%) pts...Median follow-up was 11.2 months (mo). Response rate was 68.3%, disease control rate 86.6%. mPFS was 22.0 mo (95%CI, 11.4–32.5), mTTF 25.3 mo (95%CI, 18.9-not calculable).

Adults from mainland China with previously untreated EGFRm (Exon 19 deletion or L858R) advanced NSCLC were enrolled...Osimertinib extended median PFS by 8.0 months versus comparator EGFR TKI (17.8 vs. 9.8 months; hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.37-0.85). Median OS was 33.1 months in the osimertinib group versus 25.7 months in the comparator group (HR 0.85; 95% CI 0.56-1.29).

Patients with treatment-naive stage IV EGFR-mutated (L858R or del19) NSCLC were enrolled. Orally osimertinib 80 mg once a day for 8 weeks, followed by afatinib 20 mg once a day for 8 weeks, which was repeated alternately….The ORR and one-year survival rate were 69.6% (95% CI: 54.2%-82.3%) and 93.48% (95% CI: 81.13%-97.85%), respectively….Although current study didn’t meet the primary endpoint of one-year PFS rate, alteration therapy with osimertinib and afatinib demonstrated promising efficacy...

...consecutive patients with metastatic NSCLC-EGFR mutations, treated with Osimertinib 80 mg once daily...Among the 56 patients treated with Osimertinib, the median DFS for those who had an EGFR mutation on exon 21-L858R was 15.2 months (95% confidence interval [CI] 11.3 - 19.0 months)...The median OS was 52.6 months in the exon 21-L858R group (95% [CI] 35.4 - 69.7 months...

Data were collected between December 2017 and December 2019 for patients with EGFR mutation-positive (Del19 and L858R) NSCLC who had T790M-positive disease after first-line afatinib and subsequently received osimertinib...Overall median OS was 37.6 months (90% CI: 35.5–41.3) with a 2-year survival rate of 80% (Figure 2A). Median OS was 44.8 months (90% CI: 37.0–57.8) in Asian patients and 41.6 months (90% CI: 36.9–45.0) in patients with Del19-positive disease...

From October 2016 to January 2019, 62 pts were enrolled [31 pts osimertinib; 31 pts combination] (median age 68 (37-80); 53.2% male; 83.3% stage IV; 100% adenocarcinoma; 59.7% exon 19 deletion and 40.3% L858R; 45.2% never smoker)....Combination of osimertinib with carboplatin and pemetrexed demonstrated safety in patients with EGFR and T790M mutation-positive NSCLC and the efficacy should be validated in the future phase 3 study.

CONTRADICTING EVIDENCE: Similarly, multivariate analysis also confirmed that L858R (HR=1.70, 95% CI: 1.06–2.73, P=0.026) was independently associated with worse OS than EGFR ΔE746 mutation subtype (Table S3).

We present a 52-year-old male patient with metastatic non-small-cell lung cancer (NSCLC). The patient was found to have L858R mutation in exon 21 of the EGFR gene….osimertinib (160 mg once daily) promptly induced clinical and radiological response that continued for five months. High dose pulsed erlotinib (1500 mg weekly) improved his quality of life and extended his survival for a further four months.

This is the first case report about uniportal video-assisted thoracic surgery after induction therapy of TKI for OM-NSCLC....Next-generation sequencing found an EGFR mutation (exon 21 p.L858R missense), and osimertinib, a third-generation TKI, was used 80 mg per day as the induction therapy due to the EGFR mutation detected from the metastatic tumor. A favorable treatment response was observed of the lung tumor with lymph node regression...

A 69-year-old Caucasian female former light-smoker presented with stage IV EGFR L858R positive adenocarcinoma who developed EGFR T790M mutation after 8 month treatment of erlotinib. The patient was initiated on osimertinib with disease shrinkage after 2 months, but tumor regrowth was observed after 5 months of osimertinib treatment.