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Laura Mezquita
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FP07 - Pathology (ID 109)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP07.06 - Lung Immune Prognostic Index (LIPI) in Advanced NSCLC Patients Treated with Immunotherapy, Chemotherapy and both Combined Upfront. (ID 823)
00:00 - 00:00 | Presenting Author(s): Laura Mezquita
- Abstract
Introduction
The Lung Immune Prognostic Index (LIPI) that combines the neutrophils/[leucocytes minus neutrophils] ratio (dNLR) and lactate dehydrogenase (LDH), is associated with outcomes in pretreated advanced NSCLC patients receiving single agent immune checkpoint inhibitors (ICI). However, its role in first line treatment of advanced NSCLC patients has not been explored yet. We assessed the value of baseline LIPI in the first line setting, for ICI-monotherapy, ICI-combination or platinum-based chemotherapy alone (CT).
Methods
We retrospectively collected data of patients treated with first-line ICI between 2016 and 2019 as single agent if PD-L1 ≥50% (ICI-cohort), or in combination with a CTLA4-inhibitor (ICI+ICI cohort), or with chemotherapy (ICI+CT cohort), from 18 centers worldwide. A control cohort of patients treated with platinum-based CT (CT-cohort) was also collected between 2011 and 2019 from 2 centers. Baseline LIPI was calculated as previously reported and correlated with overall survival (OS) and progression-free survival (PFS) in each treatment cohort.
Results
Overall, 930 patients were enrolled, 561 in the ICI-cohort, 186 in the combo ICI+CT, 55 in the ICI+ICI and 128 in the CT-cohort. Median (m) follow-up was 12.5 months. In the whole cohort, median age was 66 years, 70% male, 80% had non-squamous histology, and 84% had PS ≤1. Based on LIPI (available for 792 patients): 305 (38%) were considered good, 331 (42%) intermediate and 156 (20%) poor group.
Treatment outcomes according to LIPI scores are depicted in Table 1. The LIPI poor population had significantly worse OS compared with other LIPI groups, in the whole cohort (P<0.001) as well as in the ICI monotherapy and combo ICI+CT cohorts (both P<0.0001); and in the CT cohort (P=0.004). In term of PFS, we observed correlation between LIPI groups and outcomes in the whole cohort (P<0.001) and in the ICI- monotherapy cohort (P=0.008); however, no differences were observed in the cohorts of patients receiving chemotherapy regimens, alone (P=0.08) or combined with ICI (P=0.08). The analysis by PD-L1 expression in 756 patients with available data will be presented in the Congress.
Table 1: Median OS and PFS according to LIPI subgroups. NR = non reached.
ConclusionOutcomes
LIPI
subgroups
Overall cohort
N= 925
ICI-cohort
N=558
ICI + CT-cohort
N= 185
ICI + ICI cohort
N= 55
CT-cohort
N=127
Median OS
(95% CI)
All
16.3 (14.7-18.8)
21.0 (17.1-NR)
24.7 (16.9-27.1)
20.5 (14.1-NR)
9.79 (8.3-14.4)
LIPI good, 38.5%
19.8 (17.2-25.7)
NR (NR-NR)
25.7 (25.6-NR)
33.6 (14.7-NR)
14.42 (8.9-17.9)
LIPI interm, 41.8%
15.8 (14.3-20.3)
21.2 (17.1-NR)
20.3 (12.8-NR)
14.6 (5.5-NR)
9.30 (7.0-14.5)
LIPI poor, 19.7%
6.96 (5.6-12.5)
8.5 (3.4-13.7)
6.1 (4.9-NR)
14.1 (10.3-NR)
6.1 (5.0-NR)
Global LogRank P value
<0.0001
<0.0001
<0.0001
0.4
0.004
Overall cohort
N= 909
ICI-cohort
N=543
ICI + CT-cohort
N= 185
ICI + ICI cohort
N= 54
CT-cohort
N=127
Median PFS
(95% CI)
All
6.5 (5.9-7.1)
6.3 (5.0-7.6)
8.9 (6.80-10.9)
7.2 (5.7-30.6)
5.7 (5.3-6.4)
LIPI good, 38.7%
7.0 (5.9-8.5)
6.4 (4.5-10.8)
9.8 (7.8-13.0)
9.2 (5.7-NR)
6.0 (5.3-7.8)
LIPI interm, 41.6%
6.6 (6.1-7.6)
6.6 (5.6-8.1)
10.4 (6.4-12.4)
5.5 (2.5-NR)
6.1 (4.3-7.6)
LIPI poor, 19.7%
3.6 (3.1-5.6)
3.3 (1.9-6.7)
4.5 (2.8-8.2)
7.1 (2.56- NR)
3.7 (3.4-NR)
Global LogRank P value
<0.0001
0.008
0.08
0.4
0.08
Pretreatment LIPI was prognostic in untreated advanced NSCLC patients regardless of the type of therapy. However, LIPI was associated with PFS only in patients receiving ICI-monotherapy, with no statistically significant differences in CT-containing cohorts (alone or combined with ICI). This value of LIPI to guide treatment selection should be further explored in prospective studies.
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FP07.11 - Circulating Tumor DNA (ctDNA) Clearance as a Biomarker in Patients With Locally Advanced NSCLC Following Chemoradiation (ID 1432)
00:00 - 00:00 | Author(s): Laura Mezquita
- Abstract
- Presentation
Introduction
Circulating tumor DNA (ctDNA) testing has the potential to identify patients at high risk for recurrence following completion of concurrent chemoradiation (CRT) for locally advanced non-small cell lung cancer (LANSCLC). The objective of this analysis is to examine the feasibility of ctDNA testing on a commercially available focused gene panel to predict outcomes in patients with LANSCLC.
Methods
A total of 43 patients were prospectively enrolled between 09/2017 and 10/2019. Plasma for ctDNA testing was collected at the time of CRT initiation (D1), CRT completion (V1), quarterly follow up appointments for 12 months (FU1, 2, 3 and 4 respectively) after CRT completion, and at the time of relapse (R). ctDNA analysis was performed using InVisionFirst®-Lung, to detect the presence of SNVs, indels and CNAs in 37 cancer-related genes. ctDNA clearance was defined as the absence of D1 variants at V1. Patients without detectable D1 variants or in whom V1 samples were not collected were excluded from this analysis.
Results
Nineteen of 43 patients (44%) had detectable variants at D1. In this cohort of 19 patients, the median age at diagnosis was 65 years (range 43 - 82), with the majority of patients being smokers (16/19, 84%). The stage distribution was as follows: IIA (5%), IIIA (37%), IIIB (52%) and IIIC (5%). Nine patients (47%) had squamous cell carcinoma, 7 (37%) had adenocarcinoma, and 3 (16%) had poorly differentiated or NSCLC NOS. A median of 2 mutations per sample (range 1 - 5) were detected with a median of mean allelic frequency (AF) of 0.53 (range 0.05 - 16.28) at D1. Mutations in TP53 were the most commonly detected (17/19, 89%) at D1, followed by mutations in PIK3CA (5/19, 26%), CDKN2A (4/19, 21%), and EGFR (3/19, 16%). Two patients died from non-cancer related causes before FU1 and were excluded from further analysis (1 cleared ctDNA, another did not). All (3/3) patients who did not clear ctDNA had tumor relapse with a median time to relapse of 74 days (30-238), while 50% (7/14) of those who cleared ctDNA have not relapsed after a median follow-up of 469 days (range 130-710). Median time to relapse in patients who cleared ctDNA was 217 days (range 53-587 days).
Conclusion
Our results demonstrate that it is feasible to employ ctDNA testing to identify LANSCLC patients who are at high risk for disease recurrence following CRT. This finding requires validation in future studies.
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MA03 - New and Revisited Prognostic Factors in Early Stage Lung Cancer (ID 119)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 15:30 - 16:30, Scientific Program Auditorium
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MA03.08 - Impact of COVID-19 Pandemic in the Diagnosis and Prognosis of Lung Cancer (ID 3700)
15:30 - 16:30 | Author(s): Laura Mezquita
- Abstract
- Presentation
Introduction
COVID-19 pandemic has drastically changed the management of patients with cancer. The prioritization of the healthcare towards COVID-19 patients could interfere with the initial diagnosis, resulting in delayed treatment and worse outcome. We aimed to study the incidence of lung cancer new diagnosis, severity and clinical outcomes during Covid-19-period (during-COVID) compared to the same period in 2019 (before-COVID).
Methods
Bicenter retrospective cohort study of newly diagnosed non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients before (Jan-Jun/19) and during COVID-19 (Jan-Jun/20) in Spain. Clinical data were collected. We primarily assessed the difference on new lung cancer cases between both periods, and the disease severity considering: Performance status (PS), stage and any significant complication at diagnosis. Secondarily, we assessed the 30 days-mortality rate, progression-free survival (PFS) and overall survival (OS) by period.
Results
162 newly diagnosed lung cancer patients (68% NSCLC and 32% SCLC) were enrolled, with median age of 66 years, 70% were male, 33% smokers, 25% with PS ≥2. Advanced disease was diagnosed in 50% of NSCLC and 61% SCLC; 13% of NSCLC harbored driver alterations.
During-COVID, the number of new cases diagnosed decreased by 38% (43 NSCLC; 19 SCLC), compared to before-COVID period (67 NSCLC; 33 SCLC). More symptomatic cases were new diagnosed during vs. before-COVID. The Table 1 summarized clinical data and complications of new lung cancer cases by period and histology.
In NSCLC population diagnosed during-COVID, we observed more respiratory symptoms at diagnosis (30% vs. 23% before-COVID) with mainly locally-advanced/advanced disease (82% vs. 76% before-COVID). Among the cases hospitalized, the mortality during-hospitalization was 44% (2/9) vs. 17% before-COVID.
In SCLC population diagnosed during-COVID, respiratory symptoms were more common (32% vs. 24% before-COVID), but no more aggressive disease observed in terms of stage, complications and hospitalizations. Among the 4 cases hospitalized at diagnosis, none died during-hospitalization vs. 18% before-COVID (2/11).
Overall, during-Covid the mOS was 6.7 months [95% CI, 5.4-not reached] vs. 7.9 months [95% CI, 4.7-12] before-COVID. In NSCLC, the 30-days mortality was 49% vs. 25% before-COVID; in SCLC, it was 32% vs. 18% before-COVID. Updated data and treatment outcomes will be presented in the meeting.
Conclusion
Lung cancer diagnosis has been affected during the COVID-19 pandemic with fewer cases diagnosed and more symptomatic disease compared to 2019, which seems to be associated with worse outcomes. This study is still ongoing.
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MA08 - Advances in Biomarkers for Immune Checkpoint Blockade and Targeted Therapy in Non Small Cell Lung Carcinoma (ID 166)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 16:45 - 17:45, Scientific Program Auditorium
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MA08.04 - LIPI and Outcomes of Durvalumab as Consolidation Therapy after ChRT in Patients with Locally-Advanced NSCLC (ID 1969)
16:45 - 17:45 | Author(s): Laura Mezquita
- Abstract
- Presentation
Introduction
The lung immune prognostic index (LIPI), which combines pretreatment derived neutrophils/[leukocytes minus neutrophils] ratio (dNLR) >3 and lactate dehydrogenase (LDH) > upper limit of normal (ULN), is associated with outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). We aimed to assess whether pretreatment LIPI correlates with durvalumab efficacy after concurrent chemoradiotherapy in the locally advanced setting.
Methods
Multicenter retrospective study of locally advanced NSCLC patients treated with durvalumab consolidation in 21 European/US centers from 12/2015 to 5/2020. Clinical and biological data were collected before durvalumab treatment. PD-L1 expression by immunohistochemistry was also collected at diagnosis. LIPI was calculated according to previous reports and three groups were characterized: good (dNLR≤3+LDH≤ULN), intermediate (dNLR>3 or LDH>ULN) and poor (dNLR>3+LDH>ULN). The primary endpoint was progression-free survival (PFS). Response was assessed according to the clinical routine of each center.
Results
A total of 267 patients were enrolled. One hundred eighty-five (69%) patients were male, 252 (94%) smokers, with median age of 67 [range 59-73] and 223 (98%) with Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1. 260/266 (98%) were stage III, of which 96 were IIIA, 127 stage IIIB and 37 stage IIIC. 163 (63%) had non-squamous histology and 12/131 (27%) harbored driver alterations: 5 EGFR, 4 BRAF, 3 MET, 2 ALK; missing in 136 cases. PD-L1 was ≥1% in 191/233 (82%) patients both from Europe and US, missing in 34 cases. LIPI was evaluable in 143 patients: 90 were considered good (63%), 50 intermediate (35%) and 3 (2%) as poor LIPI group. dNLR >3 was found in 47/218 (22%) and LDH > ULN in 23/143 (16%) cases. Radiotherapy was delivered concurrent in 219 (82%) of cases. No differences in clinical characteristics were found between 3 LIPI groups, including the response to previous chemoradiotherapy.
With a median follow-up of 13.4 months [95% confidence interval (CI), 12-15], the median PFS was 20 months [95% CI, 12.7-not reached (NR)]. Median PFS was 7.5 months [95% CI, 3.1-NR] for poor group vs. 10.7 months [95% CI, 5.1-NR] for intermediate group vs. 19.1 months [95% CI, 11.6-NR] for good LIPI group (P=0.020). Median overall survival (OS) was NR [95% CI 47-NR] in the entire cohort and therefore considered not mature. The first objective response rate under durvalumab was 44% (111/251), being 36% (18/50) for the intermediate-poor group and 38% (33/87) for the good group with no significant differences (P=0.099). No differences in PFS and OS between groups were found regarding PD-L1 status (P=0.5 and P=0.4, respectively).
Conclusion
Pretreatment LIPI is associated with clinical outcomes in locally advanced patients treated with durvalumab as consolidation after chemoradiotherapy. This cohort is still ongoing to confirm our preliminary findings in a larger cohort.
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OA07 - Immuno-biology and Novel Immunotherapeutics from Bench to Bed (ID 228)
- Event: WCLC 2020
- Type: Oral
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 10:30 - 11:30, Scientific Program Auditorium
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OA07.10 - Discussant (ID 4150)
10:30 - 11:30 | Presenting Author(s): Laura Mezquita
- Abstract
- Presentation
Abstract not provided
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P33 - Pathology - Immunotherapy Biomarker (ID 101)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P33.10 - Identification of Long-Responders and Fast-Progressors under Immunotherapy Based on Early Monitoring of dNLR in Advanced NSCLC Patients (ID 2519)
00:00 - 00:00 | Author(s): Laura Mezquita
- Abstract
Introduction
The dNLR score, based on [neutrophil/(leucocytes-neutrophils)] ratio (dNLR) at baseline (B) and before 2nd cycle (C2), has been correlated with immune checkpoint inhibitors (ICI) outcomes in NSCLC patients. We aimed to assess whether dNLR score can identify the different response phenotypes to ICI in NSCLC, particularly the fast-progressors (FP) and long-responders (LR) under ICI.
Methods
Advanced NSCLC patients receiving ICI between Nov.12 and Jan.19, were enrolled in Gustave Roussy. dNLR was retrospectively collected at B and C2. Patients were categorized as low vs. high-dNLR at each time-point (defined as ≤3 or >3), and the change between B and C2 (good = low at both time-points, poor = high at both time-points, mixed = different at each time-point). Response types were evaluated: a) “responder” (objective response (ORR) and progression-free survival (PFS) >6 months (mo.)), b) “LR” (ORR + PFS >12 mo. and median overall survival (OS) >24 mo.), c) “standard-progressor" (PD) (progressive disease as best response; not including FP) and d) “FP” (defined as early death within the 1st 12 weeks).
Results
469 patients were included: 65% males, 90% smokers, median age of 63, 75% performance status ≤1; adenocarcinoma histology in 66% and 12% harboring driver alterations. PD-L1 was ≥1% in 143/259 (55%), missing in 210 patients. The ORR was 19% (80/431); 15% were LR, 35% standard-PD and 13% FP. Overall, the median OS was 10.0 mo. [95% CI, 8.2-12.2]; 45.2 mo. [95% CI, 31.9-not reached] in LR, 4.2 mo. [95% CI, 3.2-5.7] in PD and 0.7 mo. [95% CI, 0.6-0.9] in FP population. dNLR (B) was high in 41% of FP vs. 44% of standard-PD vs. 27% of LR (P<0.001). dNLR (C2) was high in 81% of FP vs. 45% of PD vs. 14% of LR (P<0.001). Response phenotypes were strongly correlated with the dNLR score subgroups (table 1).
Overall
N=291
Long-responder
N=48
Responder
N=108
Standard progressor
N=116
Fast-progressor
N=16
P value Good 151 (52%) 32 (67%) 65 (60%) 52 (45%) 2 (13%) <0.001 Intermediate 71 (24%) 13 (27%) 24 (22%) 30 (26%) 3 (19%) <0.001 Poor 69 (24%) 3 (6%) 19 (18%) 34 (29%) 11 (69%) <0.001
Conclusion
The dNLR score, especially at C2, is an accessible and simple tool that can add information to radiological examination discriminating the different phenotypes of response under ICI, particularly aggressive patterns such as FP.
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P34 - Pathology - Liquid Biopsy (ID 104)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P34.06 - The Clinical Utility of Liquid Biopsy by Digital Droplet PCR in Patients with Advanced NSCLC (ID 3190)
00:00 - 00:00 | Author(s): Laura Mezquita
- Abstract
Introduction
EGFR mutations occur in 15% of Caucasian and up to 50% of Asian patients with advanced NSCLC. Tissue genomic profiling is the gold standard but the liquid biopsy is a good surrogate of the tissue for molecular diagnosis. The digital droplet PCR (ddPCR) is a rapid and low-cost liquid biopsy technique for genomic analyses. We aimed to evaluate the clinical utility of the ddPCR for genomic profiling of advanced NSCLC with EGFR mutations.
Methods
The ddPCR technique was prospectively applied in a cohort of advanced EGFR mutant (EGFRmut) NSCLC patients either at baseline or at the time of at failure to tyrosine kinase inhibitor (TKI). Ten ml of blood sample were collected and centrally analyzed. Blood samples were centrally analyzed by ddPCR. Clinical and molecular data were also recorded. We assessed the liquid biopsy sensitivity at baseline for activating EGFR mutations (EGFRmut) and at progression for activating and T790M resistance EGFR mutations.
Results
A total of 70 samples (15 collected at baseline and 55 at disease progression) were collected in 41 patients included (27 (66%) with EGFR exon 19 [Del19], 14 (34%) with EGFR exon 21 mutations [L858R], median age of 62 years, 27 (66%) were females, 27 (66%) never-smokers and 37 (90%) had adenocarcinoma). At the moment of sample collection, patients had a median number of 3 metastatic sites [range: 1-6].
At baseline, ddPCR detected 87% of cases (13/15) with an EGFRmut; 90% (9/10) and 80% (4/5) for Del19 and L858R, respectively. The 2 negative cases had single sites of progression in bone and pleura, respectively.
At disease progression, EGFRmut by ddPCR was detected in 55% (30/55); 58% (22/38) for Del19, and 47% (8/17) for L858R. Of note, brain was the most common site of progression (42%). Among the cases with activating EGFRmut detected in blood at progression after first and second generation TKI, the EGFR T790M mutation was found in 35% (6/17) samples. The median number of metastatic sites was 4 [2-4] in T790M-positive vs. 2 [1-5] in T790M-negative.
In patients with isolated central nervous system progression (iCNS), EGFRmut was detected in 33% (5/15), and 2 cases had EGFR T790M. In patients with isolated thoracic progression, 60% (9/15) had positive EGFRmut, among who one case had the EGFR T790M mutation.
Conclusion
Liquid biopsy by digital PCR is a high sensitive tool for EGFR detection at diagnosis. At progression, liquid biopsy positivity for activating and resistance mutations was more likely observed in case of systemic progression and a high tumor burden. ddPCR could be used to provide a rapid molecular result to guide treatment selection in NSCLC.
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P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P84.01 - The ARIA Study: Activity of Next-Generation ALK TKIs Based on ALK Resistance Mutations Detected by Liquid Biopsy in ALK Positive NSCLC Patients. (ID 3092)
00:00 - 00:00 | Presenting Author(s): Laura Mezquita
- Abstract
Introduction
Detection of resistance mechanisms to tyrosine kinase inhibitors (TKI), in particular ALK mutations (ALKm), could help to select the subsequent treatment in ALK-positive NSCLC patients. Liquid biopsy can identify these ALKm from ctDNA in up to 29% of patients after 2nd-generation TKI-failure. We assessed the activity of next-gen TKIs based on the presence of ctDNA ALKm.
Methods
Patients with ALK-positive advanced NSCLC pretreated with 1st and/or 2nd-generation ALK-TKI were selected in 9 European centers. Liquid biopsy was collected immediately before starting brigatinib or lorlatinib. ALKm were defined by commercial or homemade next-generation sequencing run on ctDNA and covering ALK exon 22/23/25. We correlated the activity of brigatinib or lorlatinib based on three ctDNA molecular groups: presence ALKm (if one: single; if ≥2: complex); other mutations and no detectable mutations. We assessed progression-free survival (PFS), objective response rate (ORR), intracranial ORR according to the clinical routine of each center and overall survival (OS).
Results
62 patients were identified, 58 evaluable at cutoff data (Jul-20): 16 before brigatinib and 42 before lorlatinib. Median age was 53 [27-80], 64% were female, 67% nonsmoker; 97% with adenocarcinoma; 7% and 10% with isolated thoracic and brain disease, respectively. The median (m) number of TKIs was 3 [2-7]; 90% received 2nd-generation TKIs. The mFU since liquid biopsy was 24.8 months. ALKm were detected in 28% (3 brigatinib; 13 lorlatinib), 9 single and 7 complex; others were detected in 17% (n=10) and none in 55% (n=32). The most common mutation was G1202R (7 before lorlatinib), followed by G1269A and F1174L in 3 cases each, all pretreated with 2nd-generation TKIs. The TKI outcomes according to the ctDNA molecular groups is summarized in table 1. In the ALKm group, lorlatinib showed an ORR of 46% and 56% of intracranial ORR with mPFS of 6.5 months (7=single/6=complex) while no responses were observed in the 3 cases treated with brigatinib, with mPFS of 3.5 months (2=single/1=complex).Those 7 cases harboring the G1202Rmut (4=complex) had an ORR of only 14% but an intracranial ORR of 50%; mPFS was 3.6 mo. No differences were observed among ctDNA molecular groups.
ConclusionOverall
ALK mutations
Others
None
BRIGATINIB
N=16
n= 3
n=3
n= 10
PFS, median (95% CI)
5.6 months
(4.27-16.79)
3.5 months
(2.63-NR)
6.2 months
(4.27-NR)
8.1 months
(4.40-NR)
12 months-PFS rate
27.3 %
(11.9-62.6)
33.3%
(6.7-100)
0%
40%
(18.7-85.5)
ORR
27%
(4/15)
0%
(0/3)
67%
(2/3)
22%
(2/9)
ORR CNS
50%
(6/12)
0%
(0/2)
100%
(2/2)
50%
(4/8)OS*, median (95% CI)
62.6 months
(31.7-not reached)
38.4 months
(31.7-NR)
62.6 months
(21 .4-NR)
NR
(24.5-NR)
LORLATINIB
N= 42
n= 13
n= 7
n= 22
PFS, median (95% CI)
7.6 months
(5.26- 11.14)
6.5 months
(3.61-NR)
7.6 months
(5.22-NR)
7.3 months
(4.63-NR)
12 months-PFS rate
29.5%
(17.7-49.1)
30%
(12.0-74.7)
28.6%
(8.9-92.2)
30%
(14.6-61.6)
ORR
38%
(16/58)
46%
(6/13)
71%
(5/7)
23%
(5/22)
ORR CNS
62%
(18/29)
56%
(5/9)
60%
(3/5)
67%
(10/15)
OS*, median (95% CI)
55.5 months
(45.0-NR)
62.6 months
(54.8-NR)
45.0 months
(24.5-NR)
NR
(41.9-NR)
PFS: progression-free survival; ORR: objective response rate; CNS: central nervous system; OS: overall survival; *since systemic therapy start
In our study, lorlatinib showed activity in heavily-pretreated patients with ALK-positive NSCLC, regardless the ctDNA molecular groups. Poor outcomes were observed for brigatinib in 3 heavily-pretreated patients with ctDNA ALKm. The recent use of 2nd-gen TKI upfront calls for similar studies to confirm if ctDNA may be a biomarker for guiding the sequential therapy.
