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.

AstraZeneca’s Tagrisso (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy has been approved in China for the 1st-line treatment of adult patients with locally advanced or metastatic 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].

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)...

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

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 the China 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....The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the ADAURA Phase III trial.

Osimertinib provided the most DFS benefits and safety profile among the 6 treatments. Considering both efficacy and toxic effect, osimertinib is a promising agent in adjuvant setting for EGFR-mutant NSCLC, especially for those with exon 19 deletion.

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...

...The tumour harbours common EGFR mutations (Del19, L858R) at start of first-line treatment...

We screened patients who were at least 21 years of age and had a histologic or cytologic diagnosis of advanced NSCLC harbouring a sensitizing EGFR mutation (Exon 19 deletion or Exon 21 L858R mutation) at the time of diagnosis….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.

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.

We performed a multicentre, prospective real-world cohort study of the first-line osimertinib. EGFR mutation-positive NSCLC patients who started first-line EGFR-TKI treatment from September 2018 to August 2020 were enrolled...Both PFS and OS were significantly better in patients with exon 19 deletion than those with exon21 L858R point mutation: PFSs were 23.5 (95%CI: 21.3-28.0) vs 16.9 (95%CI: 15.1-19.4) months (hazard ratio 0.68, 95%CI: 0.56-0.84, p=0.0002) and OSs were 44.2 (95%CI: 41.3-NR) and 36.1 (95%CI: 30.3-41.1) months (hazard ratio 0.63, 95%CI: 0.48-0.81, p=0.0004) , respectively.

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.

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.

The sequential TKI group had a significantly longer TTF than the upfront osimertinib group in overall patients (33.2 vs. 11.2 months; p = 0.007) and in the subgroup of exon 19 deletion (36.7 vs. 10.0 months; p = 0.004), but not in the subgroup of L858R (22.6 vs. 15.6 months; p = 0.37). The similar tendency was observed in PFS.... The upfront use of first-/second-generation TKI followed by osimertinib is one of the feasible and effective strategies in Japanese patients with EGFR-mutated NSCLC, especially in patients with exon 19 deletion.

CONTRADICTING EVIDENCE: We conducted a single institution IRB-approved retrospective study of Asian pts treated at NYU Perlmutter Cancer Center with stage IV NSCLC with EGFR ex19del or L858R mutations treated with osi….However, the subgroup analysis showed that the 2y OS was inferior in the 1L osi group compared to the TKI-pretreated group in pts with ex19del (HR 2.99, 95%CI 1.12 -7.96), but not in those with L858R (HR 1.29, 95%CI 0.43-3.86)....our data showed that the use of 1L osi had a lower 2y OS in Asian pts with ex19del compared to those pre-treated with TKIs, but this was not the case with L858R.

...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.

We identified 3 previously unreported uncommon EGFR exon 19delins variants. Among the 34 patients who had uncommon EGFR19delins, 24 patients received first-generation, and 10 patients received third-generation as front-line EGFR TKI therapy, the median progression-free survival (mPFS) was significantly longer for patients who received first-generation than those with third-generation (19.1 months vs 6.9 months; HR: 0.18, 95% CI: 0.062-0.507; p < 0.001)....There were 22 patients who received osimertinib therapy, the overall ORR and DCR were 54.5% and 81.8%, respectively, and the overall mPFS was 6.9 months.

Most patients were females (56.6% and 69.9%), with EGFR Del19 (66% and 64%)….In pooled arms B/C, 70% of patients received osimertinib at PD. In arm A, PFS on osimertinib was 19.5 months. The PFSR-OSI-18 was 51.1% in Arm A and 61% in pooled arms B/C. The median OS was NR in arm A vs 42.8 (95% CI: 28.6-NR) months (mo) in pooled arm B/C, with 18-months OS of 84.4% and 82.3%, respectively....In advanced EGFR mutant-NSCLC, upfront treatment with osimertinib shows a significant reduction in the risk of brain progression, with comparable OS versus the sequential treatment approach.

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.

Using real-world data from the Netherlands Cancer Registry (NCR) we assessed patients diagnosed with stage IV NSCLC with del19 or L858R mutation....Median OS was superior for del19 versus L858R (28.4 months (95% CI 25.6-30.6) versus 17.7 months (95% CI 16.1-19.5), p < 0.001....Only in the subgroup of patients with del19 and baseline BM, a benefit was observed for treatment with osimertinib....In this nationwide real-world cohort, survival of Dutch patients with advanced NSCLC and an EGFR del19 mutation was superior versus those harboring an L858R mutation. Osimertinib performed only better as first-line treatment in patients with del19 and BM.

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).

Clinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n = 183), afatinib (n = 55), or osimertinib (n = 150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR)....Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs....Osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion...

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 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 retrospectively evaluated the clinical outcomes in patients aged 75 years or older with advanced NSCLC harboring EGFR-TKI-sensitizing mutations who received first-line osimertinib....Patients with exon 19 deletions tended to have a better PFS than those with the L858R mutation...

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.

The OCEAN study was a two-cohort trial, involving 66 patients (the T790M cohort [n=40] and 1st-line cohort [n=26]) with radiotherapy-naïve CNS metastasis from sensitizing EGFR mutation-positive NSCLC….The brain metastasis-related PFS of patients with EGFR exon 19 deletion was significantly longer than that of exon 21 L858R (median 31.8 vs. 8.3 months; log-rank p=0.032)....The primary endpoint was met, and the results demonstrated the efficacy of osimertinib in patients with CNS metastasis harboring EGFR T790M mutations especially for EGFR-sensitizing mutation of exon 19 deletion.

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).

...study of patients diagnosed with metastatic NSCLC and BMs with either activating EGFR mutations or ALK rearrangements…The analysis aimed to evaluate outcomes in patients who received TKI alone versus stereotactic radiosurgery (SRS) followed by TKI versus whole brain radiotherapy (WBRT) followed by TKI. TKI therapy was separated by early (erlotinib, gefitinib, afatinib, crizotinib, or experimental) versus newer (osimertinib, alectinib, brigatinib, ensartinib, or lorlatinib) generation. In the EGFR mutated cohort, the use of newer generation TKIs and the presence of EGFR exon 19 deletion were associated with prolonged survival.

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).

...consecutive patients with metastatic NSCLC-EGFR mutations, treated with Osimertinib 80 mg once daily, were analyzed…Among the 56 patients treated with Osimertinib, the median DFS for those who had an EGFR mutation on...14.2 months for the exon 19-deletion (95% [CI], 6.0 - 22.4 months); p= 0.25....The median OS was...49.6 months for the exon 19 deletion group (95% [CI], 25.6 - 73.6 months); p= 0.58.

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...

...cohort 1, LM patients were treated with osimertinib with CSF and plasma genotyping performed before the first dosing of osimertinib (baseline, n=45);...In cohort 1, patients with EGFR exon 19 deletion showed higher median intracranial PFS (iPFS) than those with EGFR exon 21 L858R mutation (11.9 versus 2.8 months; P=0.02). 

ORR and median PFS were significantly superior with ex19del (91%; 21.9 months; 95% CI, 5.5 to 38.3) than with L858R/L861Q (43%; 5.1 months; 95% CI, 2.3 to 7.9).

In real-world clinical practice, sequential afatinib and osimertinib was associated with encouraging outcomes in patients with EGFR mutation-positive NSCLC, especially in Del19-positive patients and Asian patients.

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.

Median times on sequential and individual EGFR TKI treatments were numerically longer in patients with Del19 versus L858R mutations (overall 29.9 vs 18.8 months; afatinib 12.2 vs 9.4 months; osimertinib 15.0 vs 9.4 months) and in patients with ECOG PS 0/1 vs ≥ 2 (overall 31.3 vs 20.9 months; afatinib 12.0 vs 10.0 months; osimertinib 15.9 vs 8.4 months).

The patient was a 57-year-old male Chinese ex-smoker (10 pack-years)...showed a 6.6cm hypermetabolic lung mass and multiple regional nodal metastases...Biopsy of the tumor showed adenocarcinoma with EGFR exon 19 deletion….induction therapy with osimertinib (80mg/day) was started with the intention of considering subsequent radical chemoradiation if satisfactory tumor shrinkage was achieved. A PET/CT scan 2.5 months after osimertinib initiation showed dramatically reduced size and metabolic activity of the primary tumor and all regional nodes, with complete metabolic response observed in the nodes....At 1.2 years after completing radical chemoradiation, the patient is still receiving osimertinib and remains in complete response.

We report a 37-year-old woman with advanced non-small cell lung cancer (NSCLC) harboring an exon 19 deletion of EGFR treated with afatinib….After delivery, the mother restarted osimertinib and maintained a complete response.

We report a case of a 64-year-old male with stage IV adeno-non-small cell lung cancer (NSCLC) harboring an exon 19 deletion in the epidermal growth factor receptor (EGFR) treated with osimertinib 80 mg/d for first-line targeted therapy....After balancing the risk and benefit, osimertinib was restarted concurrently with prednisone. The patient showed neither disease progression nor a recurrence of ILD for more than 16 months....he 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%).

CONTRADICTING EVIDENCE: …the patient received osimertinib therapy. Although this maintained the stable disease status for 4 months, rapid progression of the right pleural metastasis occurred subsequently. A CT-guided biopsy of the pleura was performed, and LCNEC characterized by positive CEA and synaptophysin staining was identified by histologic examination (Fig. 2). Molecular analysis revealed the EGFR exon 19 deletion without T790M mutation.

...multiple tumors throughout all lobes of the lung in both del19 and L860R mice. Time to tumor formation occurred within 4-12 weeks. Importantly, treatment of the mice with osimertinib resulted in tumor shrinkage and improvement in the health of mice.

Discovery and biological evaluation of proteolysis targeting chimeras (PROTACs) as an EGFR degraders based on osimertinib and lenalidomide....The bioassay results indicated that 16c has a good inhibition in PC9 cells and H1975 cells, and the corresponding IC50 value was 0.413 μM and 0.657 μM, respectively. Western blotting results demonstrated that compound 16c could serve as an effective EGFRdel19-targeting degrader in PC9 cells.