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Charu Aggarwal



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    ES02 - Management of Oncogene Addicted Patients with Stage III NSCLC (ID 5)

    • Event: WCLC 2019
    • Type: Educational Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
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      ES02.03 - Management of Other Non EGFR Oncogene Addicted Tumors (Now Available) (ID 3157)

      10:30 - 12:00  |  Presenting Author(s): Charu Aggarwal

      • Abstract
      • Presentation
      • Slides

      Abstract

      Stage III non-small cell lung cancer accounts for heterogeneous group of diseases, due to differences in tumor size, location number of nodes involved, and lymph node station involved. Stage III non-small cell lung cancer comprises 2 distinct stages, stage IIIA and IIIB disease that have different prognosis, and are usually treated differently. Approximately 15% of all patients with newly diagnosed non-small cell lung cancer present with stage III disease. Options for stage III non-small cell lung cancer include surgery, with lobectomy or pneumonectomy depending on the tumor stage, and lymph node involvement. Chemotherapy may be administered in the neoadjuvant, concurrent or adjuvant setting. Radiation therapy can be given in a concurrent, sequential approach, or may be administered in the postoperative fashion. Combination approaches are often used, and due to the significant need of multi-modality therapy, treatment decisions are usually made in a multidisciplinary setting. The optimal therapeutic approach for patients with stage IIIA non-small cell lung cancer remains controversial. For subset of patients with T3 to T4 N0-1 disease, and superior sulcus location, surgery remains a viable and preferred option. However, the optimal treatment for patients with stage III A, with bulky lymph node involvement, or multi station lymph node involvement including N2 disease, remains an area of ongoing controversy. Tri-modality approaches using preoperative chemotherapy, or upfront chemoradiation therapy followed by surgery have been evaluated (1). For patients with surgically unresectable, or medically inoperable disease, concurrent chemoradiation therapy has been established as the standard of care for patients spanning the spectrum of stage IIIA and IIIB disease.

      Recently, the PACIFIC trial demonstrated an improvement in progression free survival and overall survival with the administration of durvalumab as consolidation therapy (regardless of PDL-1 status) for patients who had not progressed after 2 or more cycles of definitive concurrent platinum-based chemoradiation therapy (2, 3). This approach represents a new paradigm in the management of unresectable NSCLC, and has now been adopted as standard of care.

      Management of Stage III patients with non EGFR oncogene addicted tumors is an area of active research. ALK or ROS directed oral tyrosine kinase inhibitors (TKIs) are not typically administered in the adjuvant setting outside of a clinical trial. There are several trials evaluating the use of targeted therapies. ALINA, is one such trial, that is a phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive ALK positive NSCLC (4). Another study is comparing adjuvant alectinib versus adjuvant platinum-based chemotherapy in patients with ALK positive NSCLC, here the alectinib is administered for 2 years (NCT 03456076). The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing (ALCHEMIST) trial is actively enrolling patients with operable NSCLC and will perform genetic screening of their tumors. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo versus erlotinib or crizotinib, respectively (NCT02194738). We await the results of these trials prior to routine incorporation of molecularly directed therapy in the management of locally advanced disease.

      References:

      1. Albain KS, Swann RS, Rusch VW, Turrisi AT, 3rd, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009;374(9687):379-86. Epub 2009/07/28. doi: 10.1016/S0140-6736(09)60737-6. PubMed PMID: 19632716; PubMed Central PMCID: PMC4407808.

      2. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. The New England journal of medicine. 2017;377(20):1919-29.

      3. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. 2018; 379:2342-2350

      4. Solomon BJ, Ahn JS, Barlesi F et al. ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol 37, 2019 (suppl; abstr TPS8569)

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    MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
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      MA11.11 - STK11/LKB1 Genomic Alterations Are Associated with Inferior Clinical Outcomes with Chemo-Immunotherapy in Non-Squamous NSCLC (Now Available) (ID 2898)

      14:00 - 15:30  |  Author(s): Charu Aggarwal

      • Abstract
      • Presentation
      • Slides

      Background

      Addition of pembrolizumab (P) to platinum-doublet chemotherapy [carboplatin (or cisplatin) and pemetrexed (CP)] prolongs overall survival and is a standard of care (SOC) for the 1st line treatment of metastatic EGFR/ALK wild-type (wt) non-squamous non-small cell lung cancer (mnsNSCLC). Despite widespread use of the CPP regimen, molecular determinants of clinical benefit from the addition of P to CP remain poorly defined. We previously identified genomic alterations in STK11/LKB1 as a major driver of primary resistance to PD-1/PD-L1 blockade in mnsNSCLC. Here, we present updated data on the impact of STK11/LKB1 alterations on clinical outcomes with CPP chemo-immunotherapy from a large retrospective multi-institution international study.

      Method

      620 pts with mnsNSCLC and tumor genomic profiling encompassing STK11/LKB1 from 21 academic institutions in the US and Europe were included in this study. Clinical outcomes were collected for two distinct patient cohorts: a) 468 pts treated with first-line CPP (or >1st line following FDA-approved TKIs) that were alive for 14 days thereafter and b) 152 STK11/LKB1-mt pts that received CP prior to regulatory approval of CPP.

      Result

      Among 468 CPP-treated pts, STK11/LKB1 genomic alterations (N=118) were associated with significantly shorter PFS (mPFS 5.0m vs 6.8m, HR 1.45, 95% CI 1.11 to 1.91; P=0.007) and shorter OS (mOS 10.6m vs 16.7m, HR 1.46, 95% CI 1.04 to 2.07; P=0.031) compared with STK11/LKB1-wt tumors (N=350). The likelihood of disease progression as BOR to CPP differed significantly between the two groups (29.5% vs 17%, P= 0.006). Similar results were obtained when limiting the analysis to EGFR and ALK-wt tumors (N=435) (mPFS 5.0m vs 6.9m, HR 1.48, 95% CI 1.12-1.95, P=0.006 and mOS 10.6m vs 16.7m, HR 1.45, 95% CI 1.02-2.05, P=0.036). Importantly, in pts with STK11/LKB1-mt mnsNSCLC, addition of pembrolizumab to CP did not result in significant improvement of PFS (mPFS 5.0m vs 3.9m, HR 0.82, 95% CI 0.63 to 1.07, P=0.14) or OS (mOS 10.6m vs 9.1m, HR 0.93, 95% CI 0.67 to 1.30, P=0.69) compared to CP alone.

      Conclusion

      In mnsNSCLC, STK11/LKB1 alterations define a subgroup of pts with inferior clinical outcomes with CPP and lack of benefit from the addition of pembrolizumab to CP chemotherapy. Novel therapeutic strategies are required to establish effective antitumor immunity in STK11/LKB1-mutant NSCLC.

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    MA25 - Precision Medicine in Advanced NSCLC (ID 352)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA25.04 - Blood-Based Tumor Mutation Burden as a Predictive Biomarker for Outcomes After Pembrolizumab Based First Line Therapy in Metastatic NSCLC (Now Available) (ID 2717)

      14:30 - 16:00  |  Presenting Author(s): Charu Aggarwal

      • Abstract
      • Presentation
      • Slides

      Background

      PD-1 blockade with pembrolizumab (P) as monotherapy in patients with PD-L1 TPS > 50% or in combination with platinum based chemotherapy (PC) is the current standard front-line therapy for metastatic non-small cell lung cancer (mNSCLC). We explored the correlation of blood (b) based tumor mutational burden (TMB) using circulating tumor DNA (ctDNA) with outcomes after front line P and PC therapy.

      Method

      Patients with newly diagnosed metastatic NSCLC starting standard of care front line P-based therapy were enrolled. Plasma was prospectively collected at baseline prior to initiation of P or PC therapy for mNSCLC. A 2.145 megabase (Mb) next-generation sequencing panel was used to assess bTMB. A bTMB cutoff of ≥16 mut/Mb was selected based on previously published data (Gandara et al, Nature 2018). Response was assessed using RECIST 1.1. Durable clinical benefit (DCB) was defined as complete response/ partial response/ stable disease that lasted > 6 months. Correlations were made for patient demographics, tumor characteristics, DCB, progression free survival (PFS), and overall survival (OS) using logistic regression and Cox proportional hazards models. Significance was determined at the 0.05 level.

      Result

      66 pts with mNSCLC were enrolled, median age 67 years (range 47-89), current or ex-smokers (n=61, 92%). Thirty-one patients (47%) received P (all PD-L1>50%); 35 received platinum-pemetrexed based PC. At the time of data cut off, median OS for P was 14.8 months, and not reached for PC. bTMB was evaluable for 52 patients (n=26 P, 26 PC), median bTMB was 16.8 mutations per Mb (mut/Mb, range 1.9-52.5). There was no correlation between bTMB and tumor PD-L1 (p=0.28). Median bTMB for patients achieving DCB was higher than for those with no clinical benefit, 21.3 mut/Mb vs. 12.4 mut/Mb, p=0.004. For patients with bTMB ≥ 16 mut/Mb, median PFS was 13.8 vs. 4.7 months for patients with bTMB <16 mut/Mb (HR 0.27 [0.13-0.55]). Median OS was not reached for bTMB ≥ 16 mut/Mb (HR 0.47 [0.20-1.1]). Loss of function mutations in STK11, KEAP1, or PTEN, or ERBB2 exon 20 insertion were enriched in patients with no clinical benefit. Combined score using bTMB ≥ 16 mut/Mb and mutations in STK11, KEAP1, or PTEN, or ERBB2 exon 20 insertions resulted in improved prediction for DCB; PFS HR of 0.18 [0.08-0.41] and OS HR of 0.27 [0.10-0.73].

      Conclusion

      Our early results suggest that bTMB using plasma ctDNA may predict therapeutic outcomes after first line P-based therapy in mNSCLC. Loss of function mutations in STK11/KEAP/PTEN and ERBB2 exon 20 insertion mutations appear to be negative predictors of benefit. As the sample size is limited and findings are reported on a pooled group of P and PC patients, the role of bTMB and response to P and PC based therapy separately should be validated in a larger prospective study.

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    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.01-107 - KEYNOTE-495/KeyImPaCT: Phase 2 Biomarker-Directed Study of Pembrolizumab-Based Therapy for Non–Small Cell Lung Cancer (ID 1355)

      09:45 - 18:00  |  Author(s): Charu Aggarwal

      • Abstract

      Background

      Immune checkpoint–based therapy has revolutionized the care of patients with non–small cell lung cancer (NSCLC). Pembrolizumab-based combination therapy aims to improve clinical outcomes over pembrolizumab monotherapy. Identification of biomarkers associated with improved response to different combination therapies may improve overall outcomes and yield a more precise approach to the use of immunotherapies in NSCLC. To test the clinical usefulness of a biomarker-informed, pembrolizumab-based combination therapy, this phase 2 KEYNOTE-495 trial (NCT03516981) will be carried out in patients with treatment-naive, advanced NSCLC.

      Method

      KEYNOTE-495 is a randomized, multicenter, open-label, phase 2 trial. Tumor tissue from patients with treatment-naive, advanced NSCLC will be initially screened for 2 validated, independent, next-generation biomarkers: T cell–inflamed gene expression profile (GEP) and tumor mutational burden (TMB). Based on the results of this biomarker screening, patients will be assigned to 1 of 4 groups: TMBlowGEPlow, TMBhighGEPlow, TMBlowGEPhigh, and TMBhighGEPhigh. Within each group, patients will be randomly assigned to receive pembrolizumab combined with MK-4280 (anti–LAG-3), lenvatinib, or MK-1308 (anti–CTLA-4). This is a group-sequential, adaptive randomization trial. Patients will be randomly assigned to MK-4280 or lenvatinib first, after which MK-1308 will be introduced; randomization has been modified to accommodate the delayed introduction of MK-1308. Response will be assessed by tumor imaging every 9 weeks for the first year, then every 12 weeks thereafter using RECIST v1.1. Treatment will continue for 35 cycles (~2 years). Patients in the pembrolizumab + lenvatinib arm who complete 35 treatments may continue with lenvatinib monotherapy until disease progression or toxicity. After a patient experiences disease progression or starts new anticancer therapy, the patient will be followed up and contacted every 12 weeks until death, withdrawal of consent, or study end, whichever occurs first. Safety will be monitored throughout the study and for 30 days after treatment or before initiation of a new anticancer treatment, whichever occurs first. Treatment arms may be terminated during the interim analysis because of safety, prespecified futility criteria, or both. The primary end point is investigator-assessed objective response rate (RECIST v1.1). Secondary end points are progression-free survival, overall survival, and safety. Recruitment and screening are ongoing in more than 14 countries and will continue until ~288 patients are randomly assigned across the biomarker-defined groups to determine the optimal treatment for each subgroup.

      Result

      Section not applicable

      Conclusion

      Section not applicable

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      P1.01-63 - Impact of Prior Radiation Pneumonitis on Incidence of Immunotherapy Related Pneumonitis (ID 662)

      09:45 - 18:00  |  Presenting Author(s): Charu Aggarwal

      • Abstract

      Background

      Patients with a history of radiation pneumonitis (RP) requiring steroids have generally been excluded from immuno-oncology (IO) trials of PD-1/PDL-1 monoclonal antibodies for safety concerns. The risk of IO-associated pneumonitis (IOP) in this group of patients (pts) is therefore unknown. We evaluated the frequency of IOP in pts who had prior RP.

      Method

      We evaluated all pts with non-small cell lung carcinoma (NSCLC) treated at our institution between 2011 and 2018 who were diagnosed with RP and at a later point received IO. Demographics, tumor characteristics, steroid use and outcomes were extracted from the electronic medical record. Median overall survival (mOS), median progression free survival (mPFS), and median time to treatment failure (mTTF) from the start of IO were estimated from Kaplan-Meier curves.

      Result

      We identified 29 pts: median age at diagnosis 63 yrs, 51.7% male, none had received prior targeted therapies. IO treatments were: atezolizumab (2), durvalumab (2), nivolumab (12), and pembrolizumab (13). Median time from RP diagnosis to start of IO was 14.2mo (2.2-75 mo). 23 pts (79%) had experienced prior grade ≥ 2 RP requiring steroids. Only 2 of the 29 pts (6.9%) developed IOP. Both pts had required steroids for prior RP and both received durvalumab; one pt was on prednisone ≥ 10mg at the start of IO. Both required steroid treatment of IOP, are still on IO and have not progressed (censored at 8.3mo and 9.9mo). OS and PFS after IO are similar (Table 1) whether or not pts required treatment for RP or were on prednisone ≥ 10 mg (or steroid equivalent) at the start of IO.

      Table 1: IO outcomes based on RP history and steroid use at start of IO

      RP Grade ≥ 2

      n=23 (95% CI)

      RP Grade < 2

      n=6 (95% CI)

      Prednisone ≥ 10mg

      n=7 (95% CI)

      Prednisone < 10mg

      n=22 (95% CI)

      All patients

      n = 29 (95% CI)

      mPFS (mo)

      5.44 (2.1-12.6)

      12.95 (0.95-)

      6.16 (2-)

      5.44 (2.1-)

      6.16 (2.4-)

      mOS (mo)

      6.6 (3.93-13.8)

      NR

      14.3 (5.3-)

      8 (3.4-16.8)

      8 (5.3-15)

      mTTFa (mo)

      2.3 (1.9-4.8)

      2.3 (1.9-)

      4.4 (2-)

      2.3 (1.9-10.9)

      2.75a (2-7)

      an=28: 1 pt lost to follow up after start of IO

      Conclusion

      In our cohort, the incidence of IOP after RP is low and similar to the rate of pneumonitis reported with pembrolizumab in pts with prior exposure to thoracic radiation.

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    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.04-28 - COAST: Durvalumab Alone or with Novel Agents for Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (ID 174)

      09:45 - 18:00  |  Author(s): Charu Aggarwal

      • Abstract
      • Slides

      Background

      The standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) is platinum-based chemotherapy with concurrent radiotherapy, followed by durvalumab consolidation for 12 months. When administered after completion of concurrent chemoradiotherapy (cCRT) in patients with unresectable NSCLC in the PACIFIC study, durvalumab demonstrated superior clinical outcomes vs placebo in terms of progression-free survival (PFS; hazard ratio [HR] 0.51; 95% CI: 0.41, 0.63) and overall survival (OS; HR 0.68; 99.73% CI 0.47, 0.997; p=0.0025).1 Comparing durvalumab with placebo, the 24‑month OS rate (95% CI) was 66.3% (61.7, 70.4) vs 55.6% (48.9, 61.8), median PFS was 17.2 months (13.1, 23.9) vs 5.6 months (4.6, 7.7) and objective response rate was 30.0% (25.8, 34.5) vs 17.8% (13.0, 23.6).1,2 However, despite cCRT followed by durvalumab, most patients with unresectable stage III NSCLC relapse and eventually die from NSCLC. The COAST study (NCT03822351) is a platform trial that aims to identify potential combinations of durvalumab with novel agents to improve response rates over monotherapy.

      Method

      This multidrug, randomized, phase 2 trial is evaluating the clinical activity and safety of durvalumab alone or in combination with the novel agents oleclumab (MEDI9447) and monalizumab (IPH2201) in patients with unresectable, stage III NSCLC who have not progressed following definitive cCRT. New treatment arms evaluating other durvalumab combinations may be added based on emerging preclinical and clinical data. The primary endpoint is objective response per RECIST v1.1 with monotherapy and combination therapy. Secondary endpoints include safety, efficacy (duration of response, disease control, PFS, 12-month PFS rate, OS), pharmacokinetics and immunogenicity. The COAST study is open for accrual with an estimated total target enrollment of up to 60 patients per treatment arm.

      References

      1Antonia SJ, et al. N Engl J Med 2018;379:2342–50.

      2Antonia SJ, et al. N Engl J Med 2017;377:1919–29.

      Result

      Section not applicable

      Conclusion

      Section not applicable

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-02 - Effect of Chemotherapy, Chemoimmunotherapy, and Immunotherapy on Parameters of T Cell Exhaustion in Metastatic Non-Small Cell Lung Cancer (ID 1880)

      10:15 - 18:15  |  Author(s): Charu Aggarwal

      • Abstract

      Background

      The pharmacodynamic immune response to anti-PD-1 immunotherapy can be tracked in the peripheral blood of cancer patients and is associated with response to therapy. However, it is unclear how chemotherapy and chemoimmunotherapy affect T cell activity. Given the established role of these treatments in Non-Small Cell Lung Cancer (NSCLC), we sought to compare the impact of chemotherapy, chemoimmunotherapy, and immunotherapy on T cell immunity.

      Method

      We prospectively collected blood samples in pts beginning chemotherapy, chemoimmunotherapy, or immunotherapy for metastatic NSCLC at baseline and with each cycle. Peripheral blood mononuclear cells were stained for immune markers and analyzed using 26 parameter flow cytometry. Immune response was characterized by increased expression of Ki67 on PD-1 expressing CD8 T cells. Statistical analysis was performed using paired t-test or Wilcoxon matched pairs analysis based on normality of data. All patients had CT scans with full RECIST 1.1 and tumor volume measurements.

      Result

      We analyzed 28 pts (63% female, median age = 65.5). 9 pts received chemotherapy, 12 pts immunotherapy, and 7 pts chemoimmunotherapy. Both immunotherapy (p = 0.001) and chemoimmunotherapy (p=0.016) resulted in an immune response that peaked at 3 weeks compared to baseline (Figure). No immune response was identified with chemotherapy (p=0.734). Immune response was detected in exhausted T cells (PD1+CD39+ CD8) for both immunotherapy (p =0.007) and chemoimmunotherapy (p =0.031). In addition, chemoimmunotherapy induced activation of CD27+CCR7+ memory CD8 T cells (p=0.0313), not seen with immunotherapy (p= 0.871). figure 1 wclc abstract.jpg

      Conclusion

      Chemoimmunotherapy and immunotherapy, but not chemotherapy, induced a significant immune response in the peripheral blood, peaking at 3 weeks. While immunotherapy and chemoimmunotherapy both targeted an exhausted population, chemoimmunotherapy induced an immune response in exhausted and memory T cells. We have collected more samples, and at time of the WCLC will present these data, as well as correlation with RECIST responses.

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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-26 - Outcomes in Patients with Compound Epidermal Growth Factor Receptor (EGFR) Mutations After Treatment with Tyrosine Kinase Inhibitors (TKIs) (ID 1090)

      10:15 - 18:15  |  Author(s): Charu Aggarwal

      • Abstract
      • Slides

      Background

      TKIs targeting EGFR have changed the therapeutic paradigm for patients (pts) with non-small cell lung cancer (NSCLC) harboring classic sensitizing mutations in EGFR (L858R and Exon 19del). Less is known about the efficacy of TKIs when a sensitizing mutation is co-existent with another, not resistance-associated EGFR mutation (compound EGFR mutations). We report the outcomes of pts with de novo compound EGFR mutations treated with TKIs.

      Method

      We identified pts with compound EGFR mutated NSCLC (plasma or tissue detection) treated at a single center. All disease-associated EGFR mutations were included with the exception of T790M and C797S. Time to treatment failure (TTF) was calculated from the start of TKI therapy until treatment discontinuation for any reason (i.e. disease progression, toxicity, pt choice or death). Overall survival (OS) was calculated from the start of TKI until death. Median OS (mOS) and TTF (mTTF) were estimated from Kaplan-Meier curves.

      Result

      24 pts with compound EGFR mutations were identified (median age 60, 67% female, 29% never smokers) between 2011 and 2018 (Table 1). Of the 16 (67%) who received a TKI, the most common mutation was G719X (n=9). Exon 19 deletions (del) were present in 2 patients (1 with G719X). L858R was found in 5 patients. Of the 8 pts who did not receive a TKI, 4 had early stage NSCLC that never progressed, 2 had local recurrence treated with surgery/radiation and 2 had metastatic recurrence. Among those treated with a TKI, the mTTF was 13.6 months (mo) and mOS was 32.7 mo. There was no difference in mTTF between erlotinib (n=10) and afatinib (n=6) (13.6 vs. 8.8 mo, log rank p=0.67). Median follow up was 33 mo. In 7 pts who had both baseline tissue and plasma testing, plasma detected all non-classic mutations.

      Conclusion

      The mOS and mTTF in this cohort of pts with compound EGFR mutations compare favorably to the historical progression free survival and mOS for pts with classic sensitizing mutations in EGFR treated with erlotinib or afatinib.

      Table 1: Compound EGFR mutations (n=24)

      Exon 3

      Exon 18

      Exon 19

      Exon 20

      R108K

      E709X

      del

      S768I

      V769M

      R776H

      Exon 18

      G719X

      5

      1

      8

      1

      1

      Exon 19

      del

      1

      Exon 21

      L858R

      3

      2

      L861Q

      1

      1

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