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Bruce E. Johnson
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OA06 - Updates on EGFR Targeted Perioperative Therapy and Precision Adjuvant Chemotherapy (ID 118)
- Event: WCLC 2020
- Type: Oral
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 16:45 - 17:45, Scientific Program Auditorium
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OA06.06 - Clinical/Biomarker Data for Neoadjuvant Atezolizumab in Resectable Stage IB-IIIB NSCLC: Primary Analysis in the LCMC3 Study (ID 3256)
16:45 - 17:45 | Author(s): Bruce E. Johnson
- Abstract
- Presentation
Introduction
Neoadjuvant immune checkpoint inhibitor therapies are well tolerated and may be of benefit in early-stage non-small cell lung cancer (NSCLC). Here we report clinical and biomarker data from the Phase II LCMC3 (NCT02927301) study evaluating pre-operative treatment with atezolizumab (anti-PD-L1) in patients with untreated stage IB to IIIB resectable NSCLC.
Methods
Patients had clinical stage IB-IIIB resectable NSCLC and ECOG 0/1. Patients received neoadjuvant atezolizumab 1200 mg intravenously every 3 weeks for ≤2 cycles followed by surgical resection (day 40±10). Those with clinical benefit could continue adjuvant atezolizumab for ≤12 months. The primary endpoint was major pathological response (MPR; ≤10% viable tumor cells) at surgery in patients without known EGFR/ALK mutations. Secondary endpoints included MPR by PD-L1 status, tumor mutation burden (TMB), and adverse events (AEs), including treatment-related (TRAE) and immune-related (irAE). Biomarker analyses included multiplex immunofluorescence (mIF) image analysis, whole exome sequencing, RNA sequencing and multi-parameter flow cytometry.
Results
The study included 181 NSCLC patients, of whom 159 had surgery (Table). In patients without known EGFR/ALK alterations, 30/147 (20.4% [95% CI: 14%-28%]) achieved MPR and 10/147 (6.8% [95% CI: 3%-12%]) achieved pathological complete response. The pre-surgery ORR (RECISTv1.1) was 7% (11/159), all partial responses. 143 (90%) patients had stable disease and 4 (3%) had progressive disease (missing RECIST assessment, n=1). AEs occurred in 178/181 (98%) patients, including AEs leading to discontinuation of treatment in 15/181 (8%), TRAEs in 122/181 (67%) and irAEs in 75/181 (41%). MPR was associated with PD-L1 status (clone 22C3), with 16% MPR in TPS<1% and 29% in TPS≥1% (P=0.117); MPR was 14% in TPS<50% and 37% in TPS≥50% (P=0.009). mIF showed that treatment increased the ratio of CD3+/CD8+ and GZMB+/CD8+ T-cells to CD3+/FOXP3+ cells in both tumor (n=45) and stromal (n=44) compartments, suggesting a shift toward T-cell activation. MPR was not observed in patients with known EGFR mutations (n=7; 1 additional patient did not have surgery) or ALK fusions (n=5). Median TMB was 7.2 mutations/Mb (range, 0.8-43.5) (n=53), and patients with higher TMB trended toward better pathological response. STK11/LKB1 and KEAP1 mutations were more frequent in non-MPR patients (Table). Biomarker analyses are ongoing.
Conclusion
The trial met its primary endpoint of 20% MPR with neoadjuvant atezolizumab in patients with resectable stage IB-IIIB NSCLC. Data suggest MPR was positively associated with PD-L1 expression and negatively associated with EGFR/ALK alterations. Ongoing comprehensive analyses of biomarker data will provide insights into mechanisms of immunotherapy in lung cancers.
Baseline characteristics
Underwent surgery
No surgery
(N = 22)Enrolled and dosed NSCLC patients
(N = 181)Achieved MPR
(N = 30)No MPR or MPR not determined
(N = 129)Median age (range), y
67 (39-83)
65 (37-82)
68 (46-81)
65 (37-83)
Female, n (%)
23 (77)
56 (43)
14 (64)
93 (51)
Race, n (%)
White
24 (80)
105 (83)
16 (73)
145 (81)
Black or African American
3 (10)
7 (6)
3 (14)
13 (7)
Asian
1 (3)
7 (6)
1 (5)
9 (5)
Unknown
2 (7)
8 (6)
2 (9)
12 (7)
Squamous histology, n (%)
14 (47)
45 (35)
10 (46)
69 (38)
Clinical stage, n (%)
IB
3 (10)
12 (9)
1 (5)
16 (9)
IIA
3 (10)
16 (12)
1 (5)
20 (11)
IIB
9 (30)
43 (33)
8 (36)
60 (33)
IIIA
12 (40)
49 (38)
10 (46)
72 (39)
IIIB
3 (10)
9 (7)
2 (9)
14 (8)
Tobacco use, n (%)
Current
12 (40)
16 (12)
7 (32)
35 (19)
Former
16 (53)
99 (77)
13 (59)
128 (71)
Never
2 (7)
14 (11)
2 (9)
18 (10)
TPS at screening, n (%)
≥ 50
13 (43)
25 (19)
2 (9)
40 (22)
≥ 1 to < 50
1 (3)
16 (12)
1 (5)
18 (10)
< 1
7 (23)
43 (33)
8 (36)
58 (32)
Unknowna
9 (30)
45 (35)
11 (50)
65 (36)
STK11/LKB1 mutation, n (%)b
No
17 (57)
54 (41)
3 (14)
74 (41)
Yes
1 (3)
8 (6)
0 (0)
9 (5)
Unknowna
12 (40)
67 (52)
19 (86)
98 (54)
KEAP1 mutation, n (%)b
No
16 (53)
55 (43)
3 (14)
74 (41)
Yes
2 (7)
7 (5)
0 (0)
9 (5)
Unknowna
12 (40)
67 (52)
19 (86)
98 (54)
Safety
All
Grade 3-4
Grade 5
Any AE, n (%)
178 (98)
75 (41)
6 (3)
AE leading to treatment discontinuation, n (%)
15 (8)
10 (6)
1 (1)
TRAE, n (%)
122 (67)
29 (16)
1 (1)
irAE, n (%)
75 (41)
16 (9)
1 (1)
TPS, tumor proportion score; measured with PD-L1 immunohistochemical 22C3 assay.
a Analysis ongoing at time of abstract preparation. b In these groups, 3 patients had dual STK11/LKB1 and KEAP1 mutations. None achieved MPR.
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P03 - Early Stage/Localized Disease - Clinical Trials in Progress (ID 112)
- Event: WCLC 2020
- Type: Posters
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P03.04 - Phase II Study of TKIs as Neo(adjuvant) Therapy in Stage II–III Resectable NSCLC with ALK, ROS1, NTRK or BRAFV600 Alterations (ID 1802)
00:00 - 00:00 | Author(s): Bruce E. Johnson
- Abstract
Introduction
Despite complete surgical resection, cure rates remain unacceptable in early-stage NSCLC. Trials of neoadjuvant and adjuvant chemotherapy have demonstrated a 5-year overall survival benefit of 5% for patients with resectable disease. Developing new treatment strategies to increase cures following resection is critical in this patient population. There are numerous immunotherapy trials ongoing in the neoadjuvant and adjuvant setting for patients with early-stage NSCLC. While there are a few targeted therapy trials in the adjuvant setting for patients with genetic alterations, neoadjuvant targeted therapies have remained incompletely explored in patients with potentially resectable NSCLC. Neoadjuvant trials allow for early trial read outs and in vivo efficacy assessment, which can guide adjuvant therapy options. The use of targeted therapies in patients with early-stage lung cancers with driver mutations has the potential to improve outcomes and provide an alternative treatment modality beyond immunotherapy and chemotherapy. Tyrosine kinase inhibitors (TKIs) are hypothesized to provide greater clinical benefit with a more favorable safety profile than the current standard of care platinum-based chemotherapy in the neoadjuvant setting. This ongoing Phase II umbrella study (ML41591) is designed to determine the efficacy and safety of targeted therapies for patients with stage II–III NSCLC with ALK, ROS1, NTRK or BRAFV600 alterations.
Methods
ML41591 is a Phase II, multicenter, non-randomized, open-label, umbrella study in patients with resectable stage II, IIIA, or selected IIIB NSCLC tumors that harbor fusions in ALK, ROS1, NTRK or BRAFV600 missense mutation. The study is designed to determine the efficacy and safety of targeted therapies, and to investigate potential surrogate biomarkers of response. Patients will be enrolled and assigned to treatment within the appropriate cohort:
- ALK cohort: ALK gene rearrangements - alectinib
- ROS1 cohort: ROS1 gene rearrangements - entrectinib
- NTRK cohort: NTRK1/2/3 gene rearrangements - entrectinib
- BRAF cohort: BRAFV600 mutation - vemurafenib plus cobimetinib.
Each cohort will enroll approximately 25 patients. The study will be conducted in two parts: pre-surgery neoadjuvant treatment will evaluate pathologic response to neoadjuvant TKIs in each cohort. Patients who undergo surgery and whose tumors lack radiographic progression will enter the post-surgery surveillance phase, which includes adjuvant treatment and follow-up for survival. This portion of the trial is exploratory. Patients will receive 4 cycles of chemotherapy followed by TKIs as adjuvant therapy for up to 24 months. The primary efficacy objective for this study is to evaluate the major pathological response rate for each treatment, defined as ≤10% residual viable tumor cells in the surgical resection specimens. Secondary efficacy objectives include investigator-assessed radiographic response, pathologic complete response, disease-free survival, event-free survival, overall survival and circulating-tumor DNA clearance rate. This trial will also evaluate exploratory biomarkers pre- and post-treatment in tissue and blood and their correlation with clinical outcomes.
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PL04 - A Vision for Clinical Trials in 2020 and Beyond (Japanese, Mandarin, Spanish Translation Available) (ID 145)
- Event: WCLC 2020
- Type: Plenary
- Track: N.A.
- Presentations: 1
- Moderators:
- Coordinates: 1/31/2021, 07:00 - 09:00, Scientific Program Auditorium
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PL04.03 - Evolving Challenges in Drug Development (ID 3919)
07:00 - 09:00 | Presenting Author(s): Bruce E. Johnson
- Abstract
- Presentation
Abstract
Seventeen years have now passed since three research groups discovered the association between epidermal growth factor receptor (EGFR) mutations and sensitivity to EGFR-tyrosine kinase inhibitors (TKIs) and 14 years since the discovery of the ALK translocation in non-small cell lung cancer (NSCLC) led to the development of ALK TKIs. Drug development in these genomically defined lung cancer patient subsets has continued, with second and third generation agents that have been developed against the tyrosine kinase domains of the two receptors. The latest agents yield response rates of >80% and progression-free survival of 19 months with osimertinib for those NSCLC patients with sensitizing mutations of EGFR, and nearly 3 years for those with ALK rearrangements treated with alectinib. The success of treating these patient subsets which make up 5% or more of the lung cancer population has prompted biomarker testing around the world and deployment of EGFR and ALK tyrosine kinase inhibitors around the world
Five more genomic changes have now led to US FDA approvals for agents targeting rarer events in lung cancer including ROS1 rearrangements, BRAF V600E mutations, NTRK rearrangements, RET rearrangements, and MET exon 14 skip mutations: each makes up from fewer than 1% up to 3% of lung cancer patients. These include crizotinib and entrectinib for lung cancer patients with ROS1 rearrangements, dabrafenib plus trametinib for V600E BRAF mutations, and larotrectinib & entrectinib for those with NTRK rearrangements—all approved between 2016 and 2019. The targeted agents approved in 2020 for patients with lung cancer include selpercatinib and pralsetinib for those with RET rearrangements and capmatinib for those with MET exon 14 skip mutations. These agents have all been US FDA approved based on single arms studies. The reported response rates, duration of responses, and progression-free survival in these patient subsets give us information on the outcomes needed for regulatory approval in these rare subsets of lung cancer patients.
The 8 targeted agents for these 5 oncogenic drivers which are present in less than 1% to up to 3% of patients with NSCLC have a response rate of 48-77%, a duration of response of approximately 11-35 months, and progression-free survivals of 10-28 months. These 5 oncogenic drivers, plus those lung cancer patients with EGFR sensitizing mutation and ALK rearrangements now make up 30-50% of patients in different parts of the world. Comprehensive biomarker testing in lung cancer patients known to harbor these genomic changes which can be effectively targeted has become increasingly important. Survey data from around the world show that substantial numbers of patients with lung cancer who may harbor these genomic changes are not getting comprehensive biomarker testing. This has prompted multiple professional organizations including the International Association for the Study of Lung Cancer and patient advocacy groups to call for universal comprehensive biomarker testing in our lung cancer patients around the world.
Challenges for the commercial development and deployment of these targeted agents is the cost of carrying out the appropriate trials for regulatory approval, the potential revenue from a relatively small patient subsets, and costs of the drugs to third party payors or the patients. Although the number of lung cancer patients needed for regulatory approval in these rare subsets with these specific genomic changes is small (typically around 50->100), the trials need to be carried out in multiple institutions where large numbers of patients are undergoing comprehensive biomarkers testing. The revenue generated by the sale of these targeted agents is limited by the number of lung cancer patients who have the appropriate comprehensive biomarker testing and the rarity of the mutation. For instance, there are approximately 140,000 lung cancer deaths in the US per year, nearly all from advanced disease. Assuming approximately 100,000 of these patients are potentially eligible to be treated with targeted agents at some time during their clinical course, a genomic change present in 1% of the population will give you approximately 1,000 patients eligible for the drug each year in the US. According to prices listed in https://www.drugs.com, a typical yearly course for one of these 8 targeted agents will cost >$200,000 per year. If this is the price charged and if all the charges are collected, this will yield revenues of about $200 million per year which may be a challenge to cover drug development costs. Perhaps an even greater challenge is the impact on our health care systems. If 30% of lung cancer patients are being treated with target agents that cost $200,000 per year, the costs to our health care systems will remain a challenge to sustain by our patients and third-party payors.
The ongoing revolution in the evaluation and treatment of patients with lung cancer continue to define rare patient subsets who can be effectively treated with different agents. The task of identifying these patients remain a logistical challenge and the ability of our patients and our health care systems to support the costs of these therapies will continue to tax our system.
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PS01 - Presidential Symposium (Japanese, Mandarin, Spanish Translation Available) (ID 143)
- Event: WCLC 2020
- Type: Plenary
- Track: N.A.
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 07:00 - 09:00, Scientific Program Auditorium
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PS01.05 - Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis (ID 3195)
07:00 - 09:00 | Author(s): Bruce E. Johnson
- Abstract
- Presentation
Introduction
Here we report surgical and clinical outcomes in the Phase II LCMC3 (NCT02927301) study evaluating pre-operative treatment with atezolizumab (anti-PD-L1) in untreated stage IB-IIIB resectable NSCLC.
Methods
Patients with stage IB-IIIB resectable NSCLC and ECOG PS 0/1 were eligible. Patients received neoadjuvant atezolizumab 1200 mg intravenously q3w for ≤2 cycles (days 1 and 22) followed by resection (day 40±10). Patients deemed to have benefit continued on adjuvant atezolizumab for ≤12 months. The primary endpoint was major pathological response (MPR; ≤10% viable tumor cells at surgery) in patients without EGFR/ALK+ mutations. Pre- and post-treatment positron emission tomography/computed tomography scans, pulmonary function tests and biospecimens were obtained. For safety analyses, adverse events (AEs) were classified as treatment-related (TRAE) or immune-related (irAE) and as pre-operative or post-operative (AE onset on or after date of surgery).
Results
Follow-up data from post-surgery visit were analyzed for all enrolled and dosed patients with NSCLC (N=181). Baseline characteristics were: mean age, 65.1 years; female, 93/181 (51%); current smoker, 35/181 (19%); nonsquamous histology, 112/181 (62%); and clinical stages IB (n=16), IIA (n=20), IIB (n=60), IIIA (n=71) and IIIB (n=14). In patients without EGFR/ALK mutations who underwent surgery, the MPR rate was 20% (30/147; 95% CI: 14%-28%) and the pathological complete response rate was 7% (10/147; 95% CI: 3%-12%) (see Carbone, WCLC 2020). Surgical and clinical outcomes and perioperative AEs are in the Table. Following atezolizumab, unresectability was detected pre-operatively in 22/181 (12%) and intra-operatively in 7/159 (4%). The majority of patients (151/159; 95%) had anatomic resections; only 15/101 (15%) converted to thoracotomy. Pathologic downstaging was seen in 57/181 (31%). Only 19/159 (12%) had surgery outside of protocol window. Intraoperative complications were rare (5/159; 3%). 145/159 (91%) had complete (R0) resection. Postoperative TRAEs and irAEs correlated with fewer viable tumor cells in the resected specimen (both P<0.05; Table). 30- and 30-to-90-day mortality were each 1/159 (0.6%). DFS and OS at 1 year and 18 months will be presented.
Conclusion
Neoadjuvant atezolizumab in resectable stage IB-IIIB NSCLC was well tolerated, with no safety concerns. The 20% MPR rate successfully met the primary study objective and was comparable to that with neoadjuvant cisplatin-based therapy. Following neoadjuvant atezolizumab, resection was performed (1) safely with low perioperative morbidity and mortality, (2) infrequently outside of the protocol window and (3) with high complete resection rates.
Enrolled and Dosed Patients With NSCLC
(N = 181)Clinical vs pathological staging
Pre-treatment
cStagePost-treatment pStage
ypT0N0M0
0
8 (4)
IA1
0
6 (3)
IA2
0
7 (4)
IA3
0
8 (4)
IB
16 (9)
15 (8)
IIA
20 (11)
11 (6)
IIB
60 (33)
42 (23)
IIIA
71 (39)
48 (27)
IIIB
14 (8)
8 (4)
IVA
0
2 (1)
Missing
–
4 (2)
No surgery
–
22 (12)
Patients downstaged following atezolizumab, n (%)
57 (31)
Timing of treatment and surgery
Median time from screening to first dose (range), days
15 (0-82)
Median time from enrolment to first dose (range), days
12 (1-82)
Median time from last cycle to surgical resection (range), days (n = 159)
21 (10-73)
Surgery
Stage
Pre-operative unresectable
Underwent surgery
Intra-operative unresectable
All, n (%)
22 (12)
159 (88)
7 (4)
IA, n
1
19
0
IB, n
1
15
0
IIB, n
8
52
1
IIIA, n
10
61
3
IIIB, n
2
12
3
Patients with disease progression per RECIST while on therapy and had surgery, n (%)
4 (2)
Patients with disease progression per RECIST while on therapy and did not have surgery, n (%)
9 (5)
Patients with surgery outside 10-day window, n (%)
19 (12)
Stage IA, n
2
Stage IB, n
1
Stage IIB, n
9
Stage IIIA, n
5
Stage IIIB, n
2
Median time outside window (range), days
8 (1-45)
Extent of resection
(n = 159)n (%)
Pneumonectomy
14 (9)
Bilobectomy
10 (6)
Lobectomy
125 (79)
Segmentectomy
2 (1)
Wedge
3 (2)
Other
5 (3)
Mortality
Deaths before planned surgery, n (%)a
0
Deaths ≤ 30 days after surgery, n (%)
1b (0.6)
Deaths between > 30 and ≤ 90 days after surgery, n (%)
1c (0.6)
Hospitalization
Median length of hospitalization (range), days (n = 48)
7.5 (2-68)
Intra-operative events (post hoc descriptive analysis)
Bronchial complications, n (%)
1 (1)
Vascular complications, n (%)
4 (3)
Lymphadenopathy, n (%)
46 (29)
Peripheral adhesions, n (%)
43 (27)
Peri-hilar/lobar adhesions, n (%)
42 (26)
Pathology
Completeness of resection, n (%)
R0
145 (91)
R1
7 (4)
R2
7 (4)
TRAE
Pre-operative
(n = 181)Post-operative
(n = 159)Any TRAE, n (%)
101 (56)
57 (36)
Grade 3-4
9 (5)
20 (13)
Grade 5
0
1 (1)
irAE
Pre-operative
(n = 181)Post-operative
(n = 159)Any irAE, n (%)
44 (24.3)
43 (27.0)
Grade 3-4
4 (2.2)
12 (8)
Grade 5
0
1 (0.6)
cStage, clinical stage; pStage, pathological stage; VAT, video-assisted thoracic surgery.
a Planned to occur on Day 40 ± 10 of the study. b Due to sudden death, not otherwise specified.
c Due to pneumonitis, deemed related to atezolizumab.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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PS02 - Presidential Symposium (Re-Broadcast) (Japanese, Mandarin, Spanish Translation Available) (ID 275)
- Event: WCLC 2020
- Type: Plenary
- Track: N.A.
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 18:00 - 20:00, Scientific Program Auditorium
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PS02.05 - Surgical and Clinical Outcomes With Neoadjuvant Atezolizumab in Resectable Stage IB–IIIB NSCLC: LCMC3 Trial Primary Analysis (ID 4286)
18:00 - 20:00 | Author(s): Bruce E. Johnson
- Abstract
Introduction
Here we report surgical and clinical outcomes in the Phase II LCMC3 (NCT02927301) study evaluating pre-operative treatment with atezolizumab (anti-PD-L1) in untreated stage IB-IIIB resectable NSCLC. Methods
Patients with stage IB-IIIB resectable NSCLC and ECOG PS 0/1 were eligible. Patients received neoadjuvant atezolizumab 1200 mg intravenously q3w for ≤2 cycles (days 1 and 22) followed by resection (day 40±10). Patients deemed to have benefit continued on adjuvant atezolizumab for ≤12 months. The primary endpoint was major pathological response (MPR; ≤10% viable tumor cells at surgery) in patients without EGFR/ALK+ mutations. Pre- and post-treatment positron emission tomography/computed tomography scans, pulmonary function tests and biospecimens were obtained. For safety analyses, adverse events (AEs) were classified as treatment-related (TRAE) or immune-related (irAE) and as pre-operative or post-operative (AE onset on or after date of surgery). Results
Follow-up data from post-surgery visit were analyzed for all enrolled and dosed patients with NSCLC (N=181). Baseline characteristics were: mean age, 65.1 years; female, 93/181 (51%); current smoker, 35/181 (19%); nonsquamous histology, 112/181 (62%); and clinical stages IB (n=16), IIA (n=20), IIB (n=60), IIIA (n=71) and IIIB (n=14). In patients without EGFR/ALK mutations who underwent surgery, the MPR rate was 20% (30/147; 95% CI: 14%-28%) and the pathological complete response rate was 7% (10/147; 95% CI: 3%-12%) (see Carbone, WCLC 2020). Surgical and clinical outcomes and perioperative AEs are in the Table. Following atezolizumab, unresectability was detected pre-operatively in 22/181 (12%) and intra-operatively in 7/159 (4%). The majority of patients (151/159; 95%) had anatomic resections; only 15/101 (15%) converted to thoracotomy. Pathologic downstaging was seen in 57/181 (31%). Only 19/159 (12%) had surgery outside of protocol window. Intraoperative complications were rare (5/159; 3%). 145/159 (91%) had complete (R0) resection. Postoperative TRAEs and irAEs correlated with fewer viable tumor cells in the resected specimen (both P<0.05; Table). 30- and 30-to-90-day mortality were each 1/159 (0.6%). DFS and OS at 1 year and 18 months will be presented. Conclusion
Neoadjuvant atezolizumab in resectable stage IB-IIIB NSCLC was well tolerated, with no safety concerns. The 20% MPR rate successfully met the primary study objective and was comparable to that with neoadjuvant cisplatin-based therapy. Following neoadjuvant atezolizumab, resection was performed (1) safely with low perioperative morbidity and mortality, (2) infrequently outside of the protocol window and (3) with high complete resection rates.
Enrolled and Dosed Patients With NSCLC
(N = 181)Clinical vs pathological staging
Pre-treatment
cStagePost-treatment pStage
ypT0N0M0
0
8 (4)
IA1
0
6 (3)
IA2
0
7 (4)
IA3
0
8 (4)
IB
16 (9)
15 (8)
IIA
20 (11)
11 (6)
IIB
60 (33)
42 (23)
IIIA
71 (39)
48 (27)
IIIB
14 (8)
8 (4)
IVA
0
2 (1)
Missing
–
4 (2)
No surgery
–
22 (12)
Patients downstaged following atezolizumab, n (%)
57 (31)
Timing of treatment and surgery
Median time from screening to first dose (range), days
15 (0-82)
Median time from enrolment to first dose (range), days
12 (1-82)
Median time from last cycle to surgical resection (range), days (n = 159)
21 (10-73)
Surgery
Stage
Pre-operative unresectable
Underwent surgery
Intra-operative unresectable
All, n (%)
22 (12)
159 (88)
7 (4)
IA, n
1
19
0
IB, n
1
15
0
IIB, n
8
52
1
IIIA, n
10
61
3
IIIB, n
2
12
3
Patients with disease progression per RECIST while on therapy and had surgery, n (%)
4 (2)
Patients with disease progression per RECIST while on therapy and did not have surgery, n (%)
9 (5)
Patients with surgery outside 10-day window, n (%)
19 (12)
Stage IA, n
2
Stage IB, n
1
Stage IIB, n
9
Stage IIIA, n
5
Stage IIIB, n
2
Median time outside window (range), days
8 (1-45)
Extent of resection
(n = 159)n (%)
Pneumonectomy
14 (9)
Bilobectomy
10 (6)
Lobectomy
125 (79)
Segmentectomy
2 (1)
Wedge
3 (2)
Other
5 (3)
Mortality
Deaths before planned surgery, n (%)a
0
Deaths ≤ 30 days after surgery, n (%)
1b (0.6)
Deaths between > 30 and ≤ 90 days after surgery, n (%)
1c (0.6)
Hospitalization
Median length of hospitalization (range), days (n = 48)
7.5 (2-68)
Intra-operative events (post hoc descriptive analysis)
Bronchial complications, n (%)
1 (1)
Vascular complications, n (%)
4 (3)
Lymphadenopathy, n (%)
46 (29)
Peripheral adhesions, n (%)
43 (27)
Peri-hilar/lobar adhesions, n (%)
42 (26)
Pathology
Completeness of resection, n (%)
R0
145 (91)
R1
7 (4)
R2
7 (4)
TRAE
Pre-operative
(n = 181)Post-operative
(n = 159)Any TRAE, n (%)
101 (56)
57 (36)
Grade 3-4
9 (5)
20 (13)
Grade 5
0
1 (1)
irAE
Pre-operative
(n = 181)Post-operative
(n = 159)Any irAE, n (%)
44 (24.3)
43 (27.0)
Grade 3-4
4 (2.2)
12 (8)
Grade 5
0
1 (0.6)
cStage, clinical stage; pStage, pathological stage; VAT, video-assisted thoracic surgery.
a Planned to occur on Day 40 ± 10 of the study. b Due to sudden death, not otherwise specified.
c Due to pneumonitis, deemed related to atezolizumab.
