P2.04-88 Surgical Outcomes of a Multicenter Phase II Trial of Neoadjuvant Atezolizumab in Resectable Stages IB-IIIB NSCLC: Update on LCMC3 Clinical Trial

Lee, J.; Chaft, Jamie E.; Nicholas, Alan; Patterson, G. A.; Waqar, Saiama N.; Toloza, Eric M.; Haura, Eric B.; Raz, Dan J.; Reckamp, Karen L.; Merritt, Robert E.; Owen, Dwight H.; Finley, David J.; McNamee, Ciaran; Blasberg, Justin D.; Garon, Edward B.; Mitchell, Jason W.; Baciewicz, Frank A.; Nagasaka, Misako; Pass, H.I.; Johnson, Angela N.; Phan, See‐Chun; Schulze, Katja; Bunn, Paul A.; Johnson, Bruce E.; Kris, Mark G.; Kwiatkowski, David J.; Wistuba, Ignacio I.; Carbone, David P.; Rusch, Valerie W.

doi:10.1016/j.jtho.2019.08.1593

Cited by 9 publications

(13 citation statements)

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“…(2019) 32 Lee et al. (2019) 21 IB–IIIB Atezolizumab (2 cycles) Day 40 ± 10 d after first dose of atezolizumab 90 (89%)/101 NR Surgery occurred outside 10-d protocol window (range: 2–43 d) in 10% (10 pts): TRAE (n = 2), surgeon availability (n = 2), other (n = 6) 11/101 (11%) (5/101 [5%; stage IIIA] had preoperative PD, 4/101 [4%] withdrew consent, 1/101 [1%] failed ECG, 1/101 [1%; stage IB] had involvement of pulmonary artery) 0% 5/101 (5%); these patients had stage IIIA or IIIB NCT02994576 PRINCEPS Besse et al. (2020) 12 I–IIIA Atezolizumab (1 cycle) 3 wk after atezolizumab and within <15 d of that window 30 (100%)/30 Median, 24 d None delayed >15 d 0% 0% 0% NCT02259621 CheckMate 159 Bott et al.…”

Section: Delays To Surgerymentioning

confidence: 99%

“…For example, in the LCMC3 study of atezolizumab monotherapy, 2% of patients had their surgery delayed by AESIs: hypothyroidism (10 d) and pneumonitis (43 d). 21 In the TOP1201 study of neoadjuvant ipilimumab plus CT, 15% of patients had delays of 28 and 35 days, respectively, owing to ipilimumab-related diarrhea 22 ( Table 2 ), described as an irAE ( Table 3 ). By contrast, in the ChiCTR-OIC-17013726 study of neoadjuvant sintilimab, 5% of patients had delayed surgery owing to TRAEs (grade 2 alanine aminotransferase and aspartate aminotransferase elevations and grade 1 hypothyroidism) but no distinction from other TRAEs was made, 23 nor was any distinction made in the MK3475-223 study of neoadjuvant pembrolizumab, in which 7% of patients had a delay owing to grade 3 treatment-related myositis.…”

Section: Delays To Surgerymentioning

confidence: 99%

“…In LCMC3, non–AE-related delays outside the protocol-specified 10-day window occurred in 8% of patients. 21 , 32 In the NEOSTAR study of nivolumab versus nivolumab plus ipilimumab, 22% of patients had their surgery delayed beyond 42 days. 13 , 33 …”

Section: Preoperative End Points In Neoadjuvant Ici Trialsmentioning

confidence: 99%

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Important Surgical and Clinical End Points in Neoadjuvant Immunotherapy Trials in Resectable NSCLC

Lee

Kim

Marjański

et al. 2021

JTO Clinical and Research Reports

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Neoadjuvant immunotherapy may improve outcomes in patients with resectable NSCLC and is being evaluated in phase 2 and 3 studies. Nevertheless, preoperative treatment postpones resection; the potential for increased surgical complexity and greater intra-and postoperative morbidity and mortality is an additional consideration. In studies primarily designed to evaluate efficacy, the impact of neoadjuvant immunotherapy on surgery is based on parameters that are poorly defined and reported differently between studies. Defining and reporting common end points among trials would improve understanding and facilitate cross-comparison of different immunotherapy regimens and may facilitate wider adoption of induction therapies by surgeons and oncologists. We propose several surgical end points and related metrics for neoadjuvant immunotherapy in resectable NSCLC. These include the periods from screening to treatment initiation and from last neoadjuvant dose to surgery; reporting of the allowable window for surgery to preclude masking delays caused by induction treatment-related toxicity; complete resection (R0) rate; preoperative downstaging; a standardized list of immune-related adverse events and associated delay to surgery; preoperative attrition; postoperative attrition before adjuvant therapy; and postoperative 30-and 90-day mortality and morbidity rates. Intraoperative end points *Corresponding author. Disclosure: Dr. Lee reports having advisory/consultancy role with AstraZeneca, Bristol Myers Squibb, Genentech, and Novartis; having a leadership role with Genentech and Novartis; receiving research grant/funding from Merck; receiving travel/accommodations/expenses support from Genentech; and receiving nonremunerated writing support from Genentech and Novartis. Dr. Kim reports having an advisory/ consultancy role with Medtronic, Olympus, and Roche/Genentech. Dr. Marjanski reports having an advisory/consultancy and speaker bureau/expert testimony role with Roche/Genentech. Dr. Falcoz reports having an advisory/consultancy role with F. Hoffmann-La Roche. Dr. Tsuboi reports having honoraria from Johnson & Johnson Japan,

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Section: Delays To Surgerymentioning

confidence: 99%

Section: Delays To Surgerymentioning

confidence: 99%

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Important Surgical and Clinical End Points in Neoadjuvant Immunotherapy Trials in Resectable NSCLC

Lee

Kim

Marjański

et al. 2021

JTO Clinical and Research Reports

View full text Add to dashboard Cite

show abstract

“…Currently, a number of phase III clinical studies of neoadjuvant immunotherapy including CheckMate 816, Keynote-671, and IMPOWER030 among others are under way. Although the potential benefit of neoadjuvant immunotherapy was seen in the early phase I/II clinical studies, some immunotherapy related concerns were also noticed (4,(11)(12)(13). For example, Figure 5 Treatment timeline of our case.…”

Section: Discussionmentioning

confidence: 88%

Consecutive severe immune-related adverse events after PD-1 inhibitor induction and surgery in locally advanced non-small cell lung cancer: a case report

Zhao¹,

Ning²,

Gu³

et al. 2021

Transl Lung Cancer Res

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Neoadjuvant PD-(L)1 inhibitors may be promising for locally advanced non-small cell lung cancer (NSCLC) with potential pathological and survival benefits. But severe immune-related adverse events (irAEs) may cause fatal consequences which require early identification and timely intervention. The basis for most of these adverse events is a reactive hyperactivated T-cell response to normal tissues that results in the production of high levels of CD4 T-helper cell cytokines or increased migration of cytolytic CD8 T cells in normal tissues. It is recommended that all patients receiving PD-(L)1 inhibitors routinely have thyroid function studies, complete blood counts, and liver function and metabolic panels at each treatment and at intervals of 6 to 12 weeks for the first 6 months after finishing treatment. Herein, we report a rare case who had two grade 3-4 irAEs consecutively occurring after PD-1 induction therapy and surgery. A 59-year-old man with stage IIIA squamous cell lung cancer receiving 3 cycles of neoadjuvant nab-paclitaxel, carboplatin, and nivolumab was reevaluated for resectability. The patient experienced acute serum transaminase elevation right after induction therapy. Seven days after surgery he had severe pneumonia. These two serious complications were both eventually relieved by a month long treatment of corticosteroids but not regular medicine which verified the diagnosis of irAEs. Although results of clinical trials of neoadjuvant immunotherapy are worth expecting, our case calls attention to careful surveillance and timely management of irAEs during the perioperative use of PD-(L)1 inhibitors. We also further discuss the standard use of corticosteroids for irAEs based on a review of literature.

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“…These studies have reported MPRs of 19%-45% for neoadjuvant ICI monotherapy, 33% for combination ICI therapy, and as high as 85% for ICI combined with chemotherapy. Phase I/II clinical studies have also demonstrated the beneficial potential of perioperative immunotherapy, although several studies 6,[14][15][16] reported AEs resulting in delayed surgery, altered surgery mode, reduced operative benefit, prolonged hospital stay, and increased economic burden on patients. Moreover, the incidence of perioperative complications and mortality was increased for patients with severe AEs.…”

Section: Introductionmentioning

confidence: 99%

Clinical recommendations for perioperative immunotherapy‐induced adverse events in patients with non‐small cell lung cancer

Hao

Zhang

et al. 2021

Thoracic Cancer

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Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non‐small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD‐1 and PD‐L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small‐scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large‐scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

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P2.04-88 Surgical Outcomes of a Multicenter Phase II Trial of Neoadjuvant Atezolizumab in Resectable Stages IB-IIIB NSCLC: Update on LCMC3 Clinical Trial

Cited by 9 publications

References 0 publications

Important Surgical and Clinical End Points in Neoadjuvant Immunotherapy Trials in Resectable NSCLC

Important Surgical and Clinical End Points in Neoadjuvant Immunotherapy Trials in Resectable NSCLC

Consecutive severe immune-related adverse events after PD-1 inhibitor induction and surgery in locally advanced non-small cell lung cancer: a case report

Clinical recommendations for perioperative immunotherapy‐induced adverse events in patients with non‐small cell lung cancer

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