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Leora Horn
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EP1.12 - Small Cell Lung Cancer/NET (ID 202)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.12-06 - New Treatment Option for ES-SCLC: Patient Characteristics and Use of an Atezolizumab Regimen in the Real-World Setting (Now Available) (ID 2651)
08:00 - 18:00 | Author(s): Leora Horn
- Abstract
Background
Results from the Phase III IMpower133 study (NCT02763579) were previously made public. Based on improvements in overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC) who received atezolizumab plus carboplatin and etoposide (IMpower133 regimen) vs chemotherapy administered in the 1L setting, the NCCN added this regimen to its guidelines (category 1, preferred) on October 10, 2018. Accordingly, some providers began implementing this regimen in their clinical practice, creating a unique opportunity to characterise its early and broad use in a real-world setting.
Method
Patients with ES-SCLC who started treatment within 90 days of initial diagnosis and had a confirmed administration of atezolizumab with carboplatin or cisplatin and etoposide (atezo regimen) on or after September 25, 2018, were included from the de-identified Flatiron Health electronic health records–derived database, representing > 280 US cancer clinics (≈ 800 sites of care). Treatment data were analysed through April 30, 2019. Broad use was defined as treatment with the atezo regimen outside of several main clinical trial restrictions (ECOG PS ≥ 2, abnormal laboratory values, cisplatin use or as 2L treatment). Frequencies and percentages are reported. Monthly uptake was defined as the percentage of ES-SCLC patients starting 1L therapy each month who were treated with the atezo regimen.
Result
Uptake of the atezo regimen increased from 10% in October 2018 to 46% in February 2019 (before FDA approval on March 18, 2019) and 66% in April 2019 (after FDA approval); 143 patients were identified, 92% of whom had ES-SCLC at initial diagnosis (Table). The atezo regimen was used broadly among 46% of patients (18% with ECOG PS ≥ 2, 18% with an abnormal laboratory value, 1% on cisplatin, 17% as 2L ES-SCLC treatment). The median time from ES-SCLC diagnosis to start of the atezo regimen was 16 days for 1L patients and 78 days for 2L patients. Patients treated with the atezo regimen in the 1L were administered atezolizumab at a median of 8 days after start of chemotherapy; those treated in the 2L were typically administered atezolizumab immediately at the start of the line.
Conclusion
This real-world analysis demonstrates the broad use of the atezo regimen, with nearly half of patients treated outside of several main IMpower133 trial restrictions. Further, a rapid uptake of the regimen even before FDA approval underscores its impact on changing clinical practice and the high unmet need of this patient population.
Table. Characteristics of Patients Treated With the Atezolizumab Plus Carboplatin/Cisplatin and Etoposide Regimen in Routine Clinical Care
Patients, n
143
Treated prior to FDA approval (March 18, 2019), n (%)
101 (71)
Median age at ES-SCLC diagnosis (IQR), years
67 (61, 73)
Aged ≥ 65 years at ES-SCLC diagnosis, n (%)
90 (63)
Female, n (%)
71 (50)
White, n (%)
100 (70)
Smoking history, n (%)
137 (96)
Stage at initial diagnosis, n (%)
LS
7 (5)
ES
132 (92)
Unknown
4 (3)
ECOG PS, n (%)a
0 or 1
76 (53)
2+
26 (18)
Unknown
41 (29)
Radiation therapy, n (%)b
14 (10)
LS setting, n
7
ES setting, n
7
Regimen, n (%)
Atezolizumab, carboplatin, etoposide
141 (99)
Atezolizumab, cisplatin, etoposide
2 (1)
Line of therapy of atezo regimen in ES setting, n (%)
1L
119 (83)
2L
24 (17)
Median time from ES-SCLC diagnosis to start of line of therapy containing atezo regimen (IQR), days
1L
16 (11, 26)
2L
78 (59, 98)
Median time from ES-SCLC diagnosis to first administration of atezo within line (IQR), days
1L
24 (14, 27)
2L
78 (59, 98)
Abnormal baseline laboratory value, n (%)c
26 (18)
1L, first line; 2L, second line; atezo, atezolizumab; ECOG, Eastern Cooperative Oncology Group; FDA, US Food and Drug Administration; IQR, interquartile range; LS, limited stage; PS, performance status.
a ECOG PS value closest to within −30 to +7 days of treatment start.
b Includes radiation therapy to chest following initial diagnosis of SCLC, including concurrent radiation therapy with systemic chemotherapy, chemotherapy followed by radiation therapy, up-front palliative radiation therapy to the chest or for superior vena cava syndrome.
c Abnormal values defined as those not meeting the following definitions: absolute lymphocyte count ≥ 500/μL, lymphocyte count ≥ 500/μL, absolute neutrophil count ≥ 1500 cells/μL, platelet count ≥ 100,000/μL, hemoglobin ≥ 9.0 g/dL, aspartate aminotransferase ≤ 5 × upper limit of normal (ULN), alanine aminotransferase ≤ 5 × ULN, alkaline phosphatase ≤ 5 × ULN, serum bilirubin ≤ 1.25 × ULN, serum creatinine ≤ 1.5 × ULN, serum calcium ≤ 12 mg/dL.
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ES22 - Immunotherapy - Discovering New Areas (ID 25)
- Event: WCLC 2019
- Type: Educational Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:Manuel Cobo, Antonio Araujo
- Coordinates: 9/09/2019, 15:45 - 17:15, Vienna (2016)
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ES22.03 - New Hope in SCLC? (Now Available) (ID 3277)
15:45 - 17:15 | Presenting Author(s): Leora Horn
- Abstract
- Presentation
Abstract
Lung cancer is the leading cause of cancer-related death worldwide. Small cell lung cancer (SCLC) accounts for approximately 15-20% of cases. This aggressive tumor is characterized by rapid growth, early development of disseminated disease and dramatic responses to first line chemotherapy. For decades, first line therapy has traditionally included four to six cycles of platinum-based chemotherapy. While up to 80% of patients respond to first-line chemotherapy, the majority eventually relapse with a median survival of 8 to 12 months for patients with extensive stage disease and 12 to 20 months for those with limited stage disease. Until recently, topotecan was the only FDA approved second line therapeutic option. The shortcomings of traditional chemotherapy, as well as the limited role of targeted therapy in SCLC, led to the investigation of novel mechanisms to target lung cancer and specifically the discovery of immune checkpoint inhibitors.
Immune checkpoint inhibitors work by blocking interactions between T cells and antigen presenting cells (APCs) or tumor cells. By inhibiting this interaction, the immune system is effectively upregulated and T-cells become activated against tumor cells. There are three major classes of checkpoint inhibitors. Ipilimumab and tremelimumab inhibit T-lymphocyte antigen-4 (CTLA-4); nivolumab and pembrolizumab target the programmed cell death-1 receptor (PD-1); and atezolizumab, durvalumab, and avelumab block PD-L1, the ligand of PD-1. Prior studies have shown lack of PD-L1 expression on tumor cells in patients with pulmonary and extra pulmonary SCLC. While PD-1 and PD-L1 are expressed in the tumor stroma of small cell carcinomas.[1] In addition PD-L1 has been shown to be prognostic in patients with SCLC.[2] The aggressive nature of SCLC is underscored by its high mutational burden, including loss of the tumor suppressor genes p53 in 75%–90% and retinoblastoma in almost 100% of tumors.[3] Higher tumor mutation burden has been associated with outcome in patients with select tumors treated with checkpoint inhibitor therapy, including non-small cell lung cancer. [4]
Recently singly agent nivolumab and combination nivolumab and ipilimumab were shown to have activity in the second and third line setting for patients with advanced SCLC with response rates of approximately 10% and 20% respectively. Combination nivolumab and ipilimumab appeared particularly promising in patients with tumors with high tumor mutation burden and in 2018 nivolumab received approval in the third line setting for patients with advanced SCLC. [5] However, disappointingly Chekckmate 331, a large phase III trial of patients who had progressed on first line platinum-based chemotherapy, found nivolumab was not superior to topotecan or amrubicin in the second line setting. Recently a combined analysis of patients treated on the Keynote 158[6] and 028 trial[7] with pembrolizumab in the second line setting demonstrated a response rate of approximately 20% in patients, with a greater benefit in patients with tumors that were PD-L1 positive.
In the first line setting, a single arm phase II trial demonstrated no benefit to maintenance pembrolizumab following induction chemotherapy in patients with advanced SCLC with a progression free survival of less than 2 months. [8] Earlier this year, a phase III trial (Checkmate 451) also found maintenance nivolumab with or without ipilimumab following induction chemotherapy in patients with advanced small cell lung cancer was not superior to placebo, suggesting this is not the optimal strategy in patients with advanced stage disease.
Importantly, he Impower 133 phase III trial demonstrated combination chemotherapy with carboplatin, etoposide and atezolizumab was superior to chemotherapy alone in patients with advanced SCLC with a significant improvement in progression free and overall survival leading to FDA approval and a new standard of care for patients with advanced disease. [9] Two large phase III trials Keynote 604 and Poseidon are comparing a similar strategy with pembrolizumab and durvalumab respectively, with data anticipated in the upcoming year.
While progress has finally been made. Limited tissue specimens in patients with SCLC remain a challenge and many unanswered questions remain including the optimal patient population in which these agents will have benefit (PD-L1 positive or negative, tumor mutation high or low), the optimal duration of therapy, the appropriate combinations (can we improve upon chemotherapy with a different checkpoint inhibitor), and the safety of these agents long term, particularly in patients with comorbid disease.
References:
1. Schultheis, A.M., et al., PD-L1 expression in small cell neuroendocrine carcinomas. Eur J Cancer, 2015. 51(3): p. 421-6.
2. Ishii, H., et al., Significance of programmed cell death-ligand 1 expression and its association with survival in patients with small cell lung cancer. J Thorac Oncol, 2015. 10(3): p. 426-30.
3. Byers, L.A. and C.M. Rudin, Small cell lung cancer: where do we go from here? Cancer, 2015. 121(5): p. 664-72.
4. Rizvi, N.A., et al., Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science, 2015. 348(6230): p. 124-8.
5. Antonia, S.J., et al., Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol, 2016. 17(7): p. 883-895.
6. Chung, H.C., et al., Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol, 2019. 37(17): p. 1470-1478.
7. Ott, P.A., et al., Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. J Clin Oncol, 2017. 35(34): p. 3823-3829.
8. Gadgeel, S.M., et al., Phase II Study of Maintenance Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC). J Thorac Oncol, 2018. 13(9): p. 1393-1399.
9. Horn, L., et al., First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med, 2018. 379(23): p. 2220-2229.
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MA06 - Challenges in the Treatment of Early Stage NSCLC (ID 124)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:Florentino Hernando-Trancho, Ayten Kayi Cangir
- Coordinates: 9/08/2019, 13:30 - 15:00, Colorado Springs (1994)
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MA06.07 - E1505: Adjuvant Chemotherapy +/- Bevacizumab for Early Stage NSCLC: Updated Chemotherapy Subset Analysis (Now Available) (ID 2885)
13:30 - 15:00 | Author(s): Leora Horn
- Abstract
- Presentation
Background
Adjuvant chemotherapy (chemo) for resected early stage NSCLC provides modest survival benefit with limited comparison data between regimens. From this trial we previously reported that adding bevacizumab (B) to adjuvant chemo failed to improve either disease free survival (DFS) or overall survival (OS). Here we update outcomes by chemotherapy regimen with an additional 30 months of follow-up.
Method
Enrolled patients with resected early stage NSCLC, stratified by stage, histology, sex, and chemo option, were randomized 1:1 to chemo alone or with B (15 mg/kg every 3 weeks for up to 1 year). Chemo consisted of a planned 4 cycles of every 3 week cisplatin with either vinorelbine (V), docetaxel (D), gemcitabine (G) or pemetrexed (P).
Result
From July 2007 to September 2013, 1501 patients were enrolled with this distribution of chemo: V 25.0%, D 22.9%, G 18.9% and P 33.2%. P was added in 2009 and restricted to non-squamous (NSq) pts. Chemo regimen was chosen (not randomized). Arms were well balanced for known prognostic factors; 28% had Sq histology. Median f/up per chemo group is: V 83.5 months(m); D 89.9m; G 87.8m; P 71.9m. In pooled analysis DFS differed by histology ranging from 29.9m(G)-43.5m(V) for NSq and 59.4m(V)-77.3m(G) for Sq. OS also differed by histology ranging from 80m(D)-98.8m(P) for NSq and 98m(G)-119m(V) for Sq. A non-significant decline in both DFS and OS was seen when B was added to D or V regimens, regardless of histology. Conversely, the addition of B to P improved both DFS (HR 0.74, p= .00994) and OS (HR 0.65, p= .00368). We thus compared outcomes across non-B regimens and though numerical differences were seen in median DFS and OS, these failed to reach statistical significance. Toxicity details were presented previously.
Conclusion
B did not improve OS when added to adjuvant chemo for patients with surgically resected early stage NSCLC, though variable DFS and OS outcomes by chemotherapy regimen have emerged with longer-term follow-up. These include a significant positive improvement in DFS and OS with B combined with P and trends of worse outcomes when B was added to other regimens. Ongoing molecular analysis of samples will hopefully elucidate the etiology of these differences.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-127 - Antitumor Activity of the Oral EGFR/HER2 Inhibitor TAK-788 in NSCLC with EGFR Exon 20 Insertions (ID 1302)
09:45 - 18:00 | Author(s): Leora Horn
- Abstract
Background
We report results of a phase 1/2 open-label, multicenter study of TAK-788 (NCT02716116), an oral investigational EGFR/HER2 inhibitor.
Method
Patients with advanced, previously treated NSCLC received daily TAK-788 in dose escalation and expansion cohorts based on tumor genotype. Antitumor activity was determined for patients with EGFR exon 20 insertions who received TAK-788 160 mg QD. Safety is reported for all patients across all doses and at 160 mg. To improve gastrointestinal tolerability, food intake instructions in this ongoing study were amended to allow for administration with or without a low-fat meal based on emerging clinical pharmacokinetic data in a healthy volunteer study (data on file).
Result
As of 14 Sep 2018, 101 patients (median age, 61 y; female, 70%; ≥2 prior anticancer therapies, 76%; brain metastases, 53%) were treated with TAK-788 at 5–180 mg QD. RP2D was determined to be 160 mg QD. 28 patients with EGFR exon 20 insertions were treated with 160 mg QD during dose escalation or in expansion cohort 1 (3.6 months on treatment; 3.8 treatment cycles [medians]); 24 patients remain on treatment. At data cutoff, best response (RECIST v1.1) among 26 patients with ≥1 disease assessment was PR, n=14; SD, n=9; and PD, n=1 (objective response rate, 54%; 95% CI: 33.4%–73.4%); 2 patients were unevaluable. 7/14 objective responses (all PR) were confirmed (6 awaiting confirmation; 1 unconfirmed PR at 160 mg QD); median time to response in these 14 patients was 56 days. 23/26 patients (89%; 95% CI: 69.9%–97.6%) achieved disease control. 23/24 evaluable patients with EGFR exon 20 insertions treated at 160 mg QD had decreased target lesion measurements (median best percent change, -32.6% [-79.1%–3.8%]). Most common TEAEs (≥20%) in patients treated with 160 mg QD: diarrhea (85%), rash (43%), nausea (41%), vomiting (30%), decreased appetite (28%), stomatitis (22%); grade ≥3 TEAEs (≥5%): diarrhea (26%); hypokalemia, nausea, stomatitis (7% each). Among patients treated with 160 mg QD, median dose intensity was 93%, rate of dose reduction due to AEs was 21.7%, and rate of treatment discontinuation due to AEs was 10.9%. There was no clear trend that response to TAK-788 was enriched in any single EGFR exon 20 insertion variant.
Conclusion
In NSCLC patients with EGFR exon 20 insertions, TAK-788 demonstrated antitumor activity and a safety profile consistent with other EGFR TKIs.
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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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P1.04-17 - Phase I/II Study of Nivolumab and Vorolanib in Patients with Refractory Thoracic Tumors (ID 2443)
09:45 - 18:00 | Presenting Author(s): Leora Horn
- Abstract
Background
Single-agent nivolumab has limited efficacy in thoracic tumors. The antitumor activity of VEGF TKIs is typically attributed to their effect on angiogenesis; however, emerging data suggest these agents can modulate the immune system, especially in the immune suppressive microenvironment. Preliminary results in multiple solid tumors demonstrated clinical benefit when nivolumab was added to anti-angiogenic agents albeit with increased toxicities. Vorolanib was designed to improve the safety profile without compromising efficacy. No dose-limiting toxicities (DLTs) from vorolanib were reported in multiple single-agent phase I trials.
Method
NCT03583086 is an ongoing multi-institutional, phase I/II study of nivolumab and vorolanib in patients with thoracic tumors who have failed at least one prior line of therapy. A standard 3+3 dose escalation design was planned with three doses of vorolanib (200, 300, and 400 mg once-daily) and 240 mg nivolumab every two weeks to determine the maximum tolerated dose. Phase II will evaluate the response rate in five cohorts: PD-1/PD-L1 naïve non-small cell lung cancer (NSCLC), PD-1/PD-L1 primary refractory (defined as progression on PD-1/PD-L1 therapy within 12 weeks), NSCLC patients with acquired resistance (achieved at least stable disease and then progressed) to PD-1/PD-L1, thymic carcinoma, and small cell lung cancer patients who have progressed on prior platinum-based chemotherapy. Exploratory correlatives will assess changes in the innate and adaptive immune responses after treatment.
Result
Phase I enrolled 10 patients (eight NSCLC and two thymic cancers); one patient was not evaluable for DLT and replaced. No DLTs were observed in three patients at the first dose level of 200 mg. Vorolanib was escalated to 300 mg, and elevated ALT (Grade 3) occurred in two of six patients just beyond the DLT period but deemed clinically significant; thus, 200 mg vorolanib with 240 mg nivolumab is being evaluated in expansion cohorts. The most common adverse events were elevated ALT, AST, and lipase, diarrhea, and fatigue; most were Grade 1/2. Grade 4 hyperglycemia and elevated lipase and Grade 3 elevated serum amylase occurred in one patient each. In seven efficacy-evaluable patients (2 immunotherapy naïve NSCLC; 3 NSCLC with prior immunotherapy; 2 thymic cancer), two partial responses were observed (1 PD-1/PD-L1 naive NSCLC and 1 thymic cancer patient); the NSCLC patient was also PD-L1 negative. Three NSCLC patients with prior PD-1/PD-L1 inhibitors had tumor regression; two of these had acquired resistance and the other was primary refractory to prior immunotherapy.
Conclusion
The combination of 200 mg vorolanib and 240 mg nivolumab was generally well tolerated. Clinical activity was observed in both PD-1/PD-L1 naïve patients and those treated with prior immunotherapy. Final phase I results and available phase II data will be presented.
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-32 - Rash and Efficacy in Anaplastic Lymphoma Kinase Positive (ALK+) Non-Small Cell Lung Cancer Patients Treated with Ensartinib (ID 2382)
09:45 - 18:00 | Author(s): Leora Horn
- Abstract
Background
Ensartinib is a potent ALK small molecule tyrosine kinase inhibitor (TKI). In a phase 1/2 study, ensartinib was generally well tolerated and demonstrated good clinical activity in pts with ALK+ non-small cell lung cancer (NSCLC). This post hoc analysis sought to determine the relationship between ensartinib-related rash and clinical benefit.
Method
Adverse events (AEs) were coded using MedDRA v15.0; severity was assessed by investigators using NCI CTCAE v4.03. Objective response rate (ORR) and median progression-free survival (mPFS) were explored in the efficacy-evaluable population, which included ALK+ pts receiving ensartinib 225 mg QD who had a postbaseline response assessment.
Result
As of Feb 07, 2019, 80 pts were dosed at the phase 3 dose of 225 mg QD and were efficacy evaluable (13 were ALK TKI naive, 37 had received prior crizotinib only, and 30 had received a prior second-generation ALK TKI). Rash was the most common AE observed in 69% of pts, mostly grade 1/2. The rashes started most frequently (33%) at day 7 or 8. The most common types of rash were general rash, rash maculopapular, and rash erythematous. Rash was primarily managed with topical corticosteroids, with some dose reductions, or no intervention at all and rarely led to discontinuation (2% [n=2]). The median duration of rash was 22 days. The ORR and mPFS were better in pts with rash vs those without (ORR, 53% vs 40%; mPFS, 8.6 vs 5.7 mo; P=.0044) (Table). A multivariate Cox proportional hazards model controlling for baseline factor (eg, age, sex, ECOG PS, and prior ALK TKI) revealed a correlation between rash and PFS (HR=0.556; P=.0755). Pts are still being accrued in this study.
Conclusion
Ensartinib was associated with mild to moderate rash that was easily managed. Preliminary findings suggest that rash is potentially associated with better clinical benefit with ensartinib.
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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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P2.04-08 - Preliminary External Validation of the Clinical Definitions of Resistance to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer (ID 2837)
10:15 - 18:15 | Author(s): Leora Horn
- Abstract
Background
Immune checkpoint inhibitors (ICIs) have become an important component of treatment for patients with advanced stage non-small cell lung cancer (NSCLC). Unfortunately, the majority of patients on ICIs will eventually progress. Based on the results from a meta-analysis review of the current ICI literature, Gillaspie et al developed a clinical radiographic response criterion to classify patients as having innate, acquired resistance or durable response to ICIs. The objective of this study was to validate this categorization using prospectively collected clinical data.
Method
The study population consisted of Stage IIIB and IV, biopsy-proven NSCLC patients from a single institution treated on or off a clinical trial with single agent ICIs in the first, second line or beyond. De-identified tumor data, stage and treatment data long with response to ICIs were collected prospectively into a database. Patients were censored at last date of follow-up if no progression had occurred. Progression-Free survival (PFS) curves and rates were estimated using the Kaplan-Meier method and then compared to the categorization established by the meta-analysis.
Result
From April 2012 to January 2018, 231 patients met criteria for inclusion and analysis. Median age was 65 years, 61% were male and 92% white. Forty-three (18.6%) received ICI in the first line, while the remaining 188 were treated in the second line or above. Analogous to the meta-analysis, our single center data demonstrated three distinct sub-populations of response. PFS curve slopes were evaluated and compared between the proposed classification and our single center experience (Table 1). The slopes of the curves are similar for the Innate, Adaptive or Acquired Resistance and Durable Response categories established in the meta-analysis. Our single-center experience resulted in a slightly steeper slope in the innate response category compared to the clinical trial literature. This may be explained by our cohort including patients who are treated in the third line or beyond whereas most of the meta-analysis trials restricted populations to either first or second line only. A steeper PFS curve would be expected in a more heavily treated population.
Table 1 PFS Slope Meta-Analysis PFS Slope Validation Innate Resistance 12.9 14.0 Aquired Resistance 3.8 3.4 Durable Response 1.2 1.1
Conclusion
This single center assessment of the proposed classification for resistance to immune checkpoint inhibitors in non-small cell lung cancer confirms the three distinct subgroups of response based on a comparison of the PFS curves. A formal statistical validation will be performed and presented. Future studies are planned to include prospectively collected data from additional comprehensive cancer centers within the validation cohort.
