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Manglio Miguel Rizzo
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EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.04-41 - Efficacy of Immunotherapy in Elderly Patients with Non-Small Cell Lung Cancer: A Multicentric Experience from Argentina (ID 1900)
08:00 - 18:00 | Author(s): Manglio Miguel Rizzo
- Abstract
Background
Immunotherapy (IO) has become a standard of care in NSCLC. Aging is associated with structural and functional changes in the immune system; hence, elderly patients could obtain less benefit from IO. Although randomized clinical trials showed benefit regardless of age, elderly are underrepresented, though its role in this population remains uncertain.
Method
We conducted a retrospective analysis of patients (pts) with NSCLC treated with IO at six centers between Nov 2013 and Feb 2019. We categorized patients in two groups (≥ 75 and < 75 years old) and evaluated overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Correlations were assessed using Fisher’s exact tests. Kaplan-Meier was used to estimate survival rates and compared using log-rank testing. Cox proportional hazard models were used to evaluate prognostic factors for PFS and OS.
Result
A total of 269 NSCLC pts treated with ICIs were included, 49 pts were ≥ 75 years old. Among them, 27 pts (55.1%) were male, 42 (85.7%) current or former smokers and 39 (79.5%) had PS 0-1; baseline brain metastases were present in 5 pts (10.2%). PDL-1 tumor proportion score (TPS) was ≥ 50% in 13/32 pts (41%), 31% received IO in first-line. There were no statistical significant differences in baseline characteristics between both groups. There was similar rate of G3-4 adverse events (18.4% vs. 17.7%, p=1.00) and treatment discontinuation (8.2% vs. 11% p=0.15, respectively) for ≥ 75 and < 75 years respectively. ORR was 18.4% (9/49) vs. 33.2% (73/220) p=0.06, DCR was 47% (23/49) vs. 65.9% (145/220) p=0.01, for ≥ 75 and < 75 years respectively. Median follow-up from IO was 15.9 months [95%CI 12.1 – 19.7]. Median PFS was 3.5 months [95%CI 2.4 – 4.6] vs. 9.8 months [95%CI 7.35 – 12.3] p<0.001 and median OS was 8.7 months [95%CI 5.4 – 12.0] vs. 18.8 months [95%CI 11.8 – 25.8] p=0.008, for ≥ 75 and < 75 years pts respectively. Histology (p=0.032), baseline corticoid treatment (p<0.001), first-line (p=0.004) and G3-4 toxicity (p=0.005) were significantly associated with OS in multivariate analysis.
Conclusion
In our cohort, immunotherapy demonstrated to be safe for elderly pts showing similar toxicity profile compared to their younger counterparts; however, elderly pts achieve less benefit than younger patients. Further assessment in larger cohorts is warranted, considering the high prevalence of lung cancer among this subset of patients.
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EP1.04-46 - Immunotherapy at Any Line Improves Survival in Hispanic Patients with Advanced Metastatic NSCLC Compared to Chemotherapy (Quijote-CLICaP) (Now Available) (ID 2776)
08:00 - 18:00 | Author(s): Manglio Miguel Rizzo
- Abstract
Background
Immunotherapy for NSCLMC offers a significant advantage to chemotherapy in selected cases. This benefit starts to disapear as the patients start two progress and requiere change in medication or even chemotherapy. The objective of this study was to compare survival outcomes of patients with advanced or metastatic NSCLC who received immunotherapy at first, second or beyond versus matched patients receiving standard chemotherapy.
Method
A retrospective multicenter international cohort study of 296 patients with unresectable/ metastatic NSCLC treated with immunotherapy either as first, second, third or fourth line was conducted. A matched comparison with a historical cohort of first line chemotherapy was conducted.
Result
Median age was 64 years (Range 34-90) and 40.2% were female patients. 91.2% of patients had an ECOG performance score ≤ 1. Immunotherapy as first line was given to 39 patients (13.7%), second line to 140 (48.8%), and as third line and beyond to 108 (37.6%). Median overall survival was 19.9 months (95% CI 14.5-22.7 months) and progression-free survival was 3.73 months (95% CI 2.8-4.2). Factors associated with increased survival included treatment as first-line (p < 0.001), type of response (p < 0.001) and PD-L1 status (p = 0.0039). Compared with the historical cohort, immunotherapy proved to be superior in terms of OS (p= 0.05) but not PFS (p= 0.2).
Conclusion
Patients who receive immune checkpoint inhibitors as part of their treatment for NSCLC have better OS compared with matched patients treated with standard chemotherapy, regardless of treatment line.
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-81 - Characterization of Hispanic Patients Who Experienced Hyperprogression During Treatment for Advanced NSCLC with Immunotherapy (ID 2922)
09:45 - 18:00 | Author(s): Manglio Miguel Rizzo
- Abstract
Background
Immunotherapy related hyperprogression is poorly characterized in Latin American patients. In this study we sought to characterize and identify factors associated with the presentation of hyperporgression after initiation of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC).
Method
A multicenter international retrospective study on 110 patients was conducted. Clinical variables as well as routine blood studies were recorded before initiation of treatment. Regression analysis was used to find associations. A random forest tree analysis (RFTA) based on continuous and discrete variables was used to subcategorize patients based on occurrence of hyperprogression.
Result
Median age was 64 years (Range 34-90) and 59.8 % were male patients. ECOG performance status was >1 on 8.8% of patients. Median overall survival was 12.7 months (95% CI 9.67-14 months) and progression-free survival of 4.27 months (95% CI 3.97-5.0). 44 hyperprogressors were documented (19.8%, [95%CI 14.5-25.1%]). Median time to progression was approximately 5 weeks after initiation of treatment. Factors associated included albumin and hemoglobin levels (p = 0.046 and 0.037 respectively), presence of CNS (p= 0.0009) and bone metastasis (p = 0.004) and weight loss (p= 0.004). RFTA revealed that a leucocyte count over 5.300 cells/dl was present in all hyperprogressors.
Conclusion
Hyperprogression is a phenomenon after initiation of immunotherapy which is associated with clinical and paraclinical variables. These associations could be used to withhold certain agents and prevent its occurrence in NSCLC treatment.
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P1.04-82 - Toxicity as a Clinical Marker for Efficacy of Immunotherapy in NSCLC: A Multicentric Experience from Argentina (Now Available) (ID 1950)
09:45 - 18:00 | Author(s): Manglio Miguel Rizzo
- Abstract
Background
Immunotherapy (IO) has become standard of care in NSCLC. Immune-related adverse events (irAEs) have shown to be associated with survival benefit in several tumor types in small reports. However, its predictive role as a clinical marker for efficacy to PD-1 inhibition in NSCLC remains uncertain.
Method
We conducted a retrospective analysis of patients (pts) with NSCLC treated with IO at six centers between Nov 2013 and Feb 2019. We categorized patients in two groups (irAEs and no-irAEs group) and evaluated overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). A 6-week cutoff was established to evaluate the impact of early vs. late onset of irAEs. Correlations were assessed using Fisher’s exact tests. Kaplan-Meier was used to estimate survival rates and compared using log-rank.
Result
A total of 269 NSCLC pts treated with ICIs were included, 48 pts (17.8%) developed Grade 3-4 irAEs. Among them, median age 66 years [range 47 - 86], 31 (65%) were male, 42 (87.5%) current or former smoker and 42 (87.5%) had PS 0-1, PDL-1 tumor proportion score (TPS) was ≥ 50% in 17/26 pts (65.4%), 5 pts (11%) received baseline corticoids; 15 pts (31%) were treated in first-line. No statistical significant differences in baseline characteristics were observed. Median follow-up from IO was 15.8 months [95%CI 12.1 – 19.7]. Median number of cycles to toxicity was 5 [range 1 – 60]. Most common grade 3-4 events were pneumonitis (n=12), adrenal insufficiency (n=7), thyroiditis (n=7), rash (n=6) and nephritis (n=6). There were 5 (10%) treatment-related deaths. Patients with irAEs had significantly higher ORR and DCR vs. no-irAEs: 48% (23/48) vs. 26.7% (59/221) p=0.005 and 83% (40/48) vs. 58% (128/221) p<0.001, respectively. Similarly, median PFS and OS were significantly prolonged in pts with irAEs vs. no-irAEs: 17.1 months [95%CI 8.1 – 25.9] vs. 6.6 months [95%CI 4.9 – 8.3] p=0.02 and 29.4 months [95%CI NR] vs. 12.9 months [95%CI 10.0 – 15.9] p=0.01, respectively. Early onset of irAEs (≤6 weeks) had significantly shorter PFS and OS vs. late onset (>6 weeks): 2.43 months [95%CI 0 - 9.02] vs 21.0 months [95%CI 14.57 - 27.44] p=0.006 and 3.94 months [95%CI NR] vs NR p=0.010, respectively.
Conclusion
In our cohort, we observed a correlation between irAEs and efficacy in NSCLC patients treated with IO. This potential predictive value needs to be validated in larger prospective cohorts to drive definitive conclusions.
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P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-10 - Real-World Efficacy of First-Line Pembrolizumab in Patients with Advanced PD-L1 High Non-Small Cell Lung Cancer in Argentina (Now Available) (ID 1440)
09:45 - 18:00 | Author(s): Manglio Miguel Rizzo
- Abstract
Background
Pembrolizumab monotherapy is a standard first-line (1L) treatment regimen for patients (pts) with non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) ≥ 50%. We aimed to study the clinical efficacy and toxicity of this approach in the real-world setting in Argentina.
Method
We conducted a retrospective, multicenter study. Patients with metastatic NSCLC and a PD-L1 TPS ≥ 50% treated in 1L with at least one dose of pembrolizumab monotherapy, from December 2016 to February 2019, were included. Data was collected from clinical records, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were estimated. Cox regression model was performed for uni- and multivariate analysis.
Result
A total of 53 pts were included. Median age (range) was 68 years (35-88), 33 (62.3%) were male, and 46 pts (86.7%) were smokers. Most tumors were lung adenocarcinoma (N=47, 88.7%), median (IQR) PD-L1 TPS was 79% (60-87.5) and 22 tumors (41.5%) had a TPS ≥ 75%. EGFR/ALK/ROS1 mutations/fusions were not detected. Brain (N=10; 18.9%), liver (N=5 (9.4%) and bone (N=15; 28.3%) metastasis were present at baseline. Performance status (PS) score was 0-1 in 46 pts (86.8%) and 7 pts (13.2%) had PS 2. Six pts received baseline corticosteroid treatment. The ORR with pembrolizumab was 41.5% (95% CI: 28.1-55.8), median PD-L1 TPS (mTPS) was significantly higher in responders (mTPS 74% vs 67%, P = 0.04). Grade ≥ 3 immune-related adverse events occurred in 7 pts (13.2%) and 10 (18.9%) required systemic therapy with steroids. With a median-follow up of 12.9 months (95% CI: 8.4-17.6), median PFS and median OS were not reached. The estimated percentage of patients alive and without progression at 6 and 12 months was 64.8% and 55.8%. The estimated percentage of patients alive at 6 and 12 months was 77.5% and 69.4%. Median PFS and OS for patients with PS 2 was 2.4 months (95% CI: 1.7-3.1) and 4.5 months (95% CI: 3.1-6.0), respectively. After adjusting for PS, a PDL1 TPS score ≥ 75% was independently associated with improved PFS in multivariate analysis [HR 0.28 (95% CI: 0.09-0.92); P = 0.03) but not with OS. PS score equal to 2 was independently associated with decreased OS [HR 4.52 (95% CI: 1.06-19.28); P = 0.04] in multivariate analysis.
Conclusion
Pembrolizumab monotherapy is tolerable and confers durable clinical benefit for patients with tumors expressing high levels of PD-L1 in the real world clinical setting. The optimal first-line immunotherapy approach for patients with PS 2 in this setting warrants further studies.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-81 - Non-Small Cell Lung Cancer Treated with Immunotherapy: Multi-Institutional Experience from Argentina (Now Available) (ID 1893)
10:15 - 18:15 | Presenting Author(s): Manglio Miguel Rizzo
- Abstract
Background
Immunotherapy (IO) has been established as the standard treatment for metastatic non-small cell lung cancer (NSCLC) patients improving survival. It has been approved both in first line and after platinum-treated patients. We aimed to study the efficacy and tolerability of anti PD-(L)1 inhibitors in pts with NSCLC in Argentina providing more evidence about efficacy and toxicity
Method
Metastatic NSCLC patients (pts) treated with immunotherapy in six hospitals between 11/2013 - 2/2019 were included. Data was collected retrospectively by the investigators. Progression-free survival (PFS) and overall survival (OS) were assessed. Cox-regression model was performed for uni- and multivariate analysis. All pts who received at least one dose of immunotherapy were evaluated for efficacy and toxicity.
Result
A total of 269 patients were included. Median age (range) was 66 ys (28-88), 164 (61%) were men, 226 (84%) were current/former smokers and 223 (82.9%) had performance status (PS) 0-1. The predominantly histology was non-squamous (N=239; 88.8%), 158 (58.7%) tumors were evaluable for PD-L1 expression and 9 (3.3%) had EGFR mutations. 86 (32%) pts received IO as first-line and 155(57.6%) as second-line therapy. Anti-PD1 antibodies were most commonly administered (83.3%). Baseline brain and liver metastases were present in 50 (18.6%) and 29 (10. 8%) pts, respectively. The overall response rate was 30.4% (76/256). The most common sites of progression were (N=261) bones 142 (54.4%), lung/lymph nodes 74 (28.4%) and brain 26 (10%), visceral 19 (7.3%). Grade ≥ 3 adverse events occurred in 48 pts (17.8%) and 28 (10.4%) pts discontinued treatment due to toxicity. With a median follow up of 15.88 months (95% CI 12.08-19.68), median PFS was 7.26 (95%CI 5.15-9.38) and OS was 15.18 (95%CI 9.47-20-90). In univariate analysis smoking status (p 0.049), PDL1 (p 0.002), PS (p 0.000), corticoid therapy at beginning of IO (p 0.001), grade≥3 toxicity (p 0.027), first line therapy (p=0.003) and driver mutation (p 0.028) were all associated with PFS. Age (p=0.030), PDL1% (p=0.007), corticoid therapy at beginning of IO (p<0.001), grade≥3 toxicity (p=0.012) and first line therapy (p=0.038) were all associated with OS. In multivariate analysis, PDL1 and PS were independently associated with both, PFS (p=0.011 and p=0.000, respectively) and OS (p=0.036 and p<0.001, respectively).
Conclusion
Treatment with anti PD-(L)1 inhibitors in the real-world is effective and tolerable, supporting the use of immunotherapy in pts with NSCLC. As previously reported, low PDL1 expression and poor PS confer worst clinical outcomes. Other factors such as age, line of treatment, corticoid use, toxicity and driver mutations may impact treatment response.
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P2.04-82 - Discontinuation of Anti-PD-1/PD-L1 Antibody Therapy in the Absence of Disease Progression: Clinical Outcomes in Advanced NSCLC (Now Available) (ID 2024)
10:15 - 18:15 | Author(s): Manglio Miguel Rizzo
- Abstract
Background
Treatment with anti PD-1/PD-L1 immune checkpoint inhibitors (ICIs) prolongs survival in patients (pts) with advanced non-small cell lung cancer (NSCLC). Treatment discontinuation in the absence of disease progression rises concern on treatment efficacy in patients and providers. We aim to study the outcomes of patients with NSCLC who discontinued treatment with ICIs.
Method
Retrospective, multicenter descriptive study. Patients diagnosed with advanced NSCLC who discontinued therapy with pembrolizumab, nivolumab or atezolizumab in the absence of disease progression (PD) between 11/2013 - 2/2019 were included. All pts who received at least one dose of immunotherapy were evaluated for efficacy and toxicity.
Result
A total of 269 patients diagnosed with metastatic NSCLC and treated with anti-PD-1 or anti-PD-L1 antibodies were retrospectively studied. Median follow-up for the entire cohort was 15.8 months (95% CI: 12.08-19.68).
Median age 66 ys (r 28-88), 61% men, 83,4% were former or current smokers. Non-squamous NSCLC was the most common histologic subtype (N=239; 89%).
Performance status (PS) was 0-1 in 223 pts (83%), 86 pts (32%) received ICIs in first line, 154 pts (57.4%) in second line and 28 pts (10.6%) in third line or beyond. Pembrolizumab was the most common treatment for pts (N= 129; 48%), followed by nivolumab (N= 113; 42%) and atezolizumab (N=27; 10%).Within the entire cohort, 39 pts (14.5%) discontinued treatment with ICIs for reasons other than PD, 35 pts due to toxicity and 4 pts for other reasons. At the time of treatment discontinuation, 3 pts (7.7%) had achieved a complete response (CR), 10 (25.6%) a partial response (PR), 17 pts (43,5%) a stable disease and 9 (23%) had PD. Median duration of response after discontinuation of ICIs was 6 months (range 0.1-27).
Of the CR + PR + SD subgroup at the time of analysis 76, 9% remain without PD.
If we consider only patients who maintained at least 3 months’ therapeutic benefit when discontinuing treatment in the absence of PD, only 3 patients had PD (at 6, 7 and 17 months of discontinuation) and the median duration of response for this group was 8 months ( 3.74-27).
Conclusion
Patients who discontinue treatment with ICI in the absence of disease progression can achieve sustainable benefit. Further studies are needed to assess the safety and efficacy of reintroducing ICIs in the event of disease progression in this population.
