ESMO Big Coffee Review Professor Xu Songtao: Neo-adjuvant immune combination "doubles" resectable lung cancer pCR! Expect long-term survival outcomes

Editor: Xiaoyuan

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The European Society for Internal Oncology Annual Meeting (ESMO) is the most prestigious and influential oncology conference
in Europe.
The 2022 ESMO Conference will be held
from September 9 to 13, 2022 in a combination of offline (Paris, France) and online.
The ESMO conference covers basic research, translational research, and the latest clinical research advances, and will provide a broad and excellent academic platform
for clinical practice, multidisciplinary discussion, and more.
A number of blockbuster studies in the field of lung cancer have been presented at this year's ESMO conference
.

In the oral presentation, Professor Iris Bahce presented the results of the Phase II INCREASE study, which explored the safety and efficacy
of neoadjuvanumab navulumab + ipimumab in patients with locally advanced non-small cell lung cancer (NSCLC).

Expert profile

Professor Xu Songtao

Doctor of Medicine, Fudan University

Department of Thoracic Surgery, Zhongshan Hospital, Fudan University

Chief Physician of Thoracic Surgery, Shanghai Geriatric Medical Center

Member of the International Association for the Study of Lung Cancer (IASLC).

He is a member of the Lung Cancer Medical Education Committee of the Chinese Medical Education Association

He is a member of the Thoracic Surgery Committee of Shanghai Association of Integrative Traditional Chinese and Western Medicine

He is a member of the Thoracic Surgery Branch of Fujian Medical Association

Participated in the development of expert consensus on molecular residual lesions of non-small cell lung cancer (2021); Expert consensus on perioperative treatment of early lung cancer (2019); Guidelines for the diagnosis and treatment of primary lung cancer (2018); Guidelines for the management of chest tubes and postoperative mechanical ventilation after lobectomy (2017)

“

Details of the Phase II INCREASE study

Professor Iris Bahce

background

Neoadjuvant chemoradiotherapy (CRT) and surgery are treatment options
for patients with locally advanced NSCLC with localized mediastinal lymph node metastases.

method

This single-arm, prospective phase II trial is planned to include 26 (critical) patients with
resectable, T3-4N0-2 NSCLC.

Study the design

outcome

To date, 15 of the 24 patients who received surgery (63%) have achieved pCR
.

Patient baseline features

Primary study endpoints

Treatment with ipimumab plus nivolumab in CRT was acceptable toxicity, with a 67%
incidence of grade 3 to 4 treatment-related adverse events.
No patients delayed surgery
due to neoadjuvant therapy.
No treatment-related deaths occurred
.

Security analysis

Neoadjuvant therapy enhances the expression of CD4+ and CD8+ cells, memory cell subsets in peripheral blood, and increases the expression of CD8+ T cell markers in tumor drainage lymph nodes
.

Neoadjuvant dual immunotherapy promotes T cell activation

conclusion

The results of the study showed that the addition of neoadjuliumab + ipimumab to CRT was safe and feasible, which could bring deep pathological remission to patients, with pCR rates and MPR rates reaching 63% and 79%,
respectively.
The study data support the inclusion of this combination regimen in locally advanced NSCLC where CRT is planned to be given, and support the exploration of efficacy of this combination regimen in non-operable patients
.

“

2022 ESMO Expert Review – Prof.
Songtao Xu

Prof.
Xu Songtao: Large oncology surgeons above T3 are a challenge, and neoadjuvant chemoradiotherapy is an important treatment option
.
The CSCO guidelines recommend neoadjuvant chemoradiotherapy (grade I recommended) for T3-4N1 superior sulcus tumors and neoadjuvant chemotherapy ± radiotherapy (grade II recommended)
for NSCLC resectable non-superior sulcus tumors with T4N0 and T3-4N1-2.
The INCREASE study, which was announced at ESMO this year, is a single-arm phase II study evaluating the safety and efficacy of neoadjuvuzumab plus ipimumab combined with simultaneous chemoradiotherapy in patients with resectable or potentially resectable locally advanced NSCLC
.
Key highlights of the study are:

The results of the study reached the predetermined primary endpoints: the pCR rate of surgical patients reached 63% (15/24 cases) and the MPR rate reached 79% (19/24 cases).

The pCR rate of traditional platinum-containing chemotherapy + 60Gy synchronous radiotherapy was about 30%, and the pCR rate of navurizumab + ipimumab was doubled, suggesting that radiotherapy and chemotherapy combined with immunotherapy could significantly improve the pathologic remission rate and depth of
remission.
Improvement in pathological remission is associated with improved survival, so EFS and OS data from the secondary endpoints of the INCREASE study are worth looking forward to
.

After immunotherapy was added to neoadjuvant chemoradiotherapy, it made up for the lack of chemotherapy as a single systemic treatment and strengthened the systemic control
of tumors.
The purpose of neoadjuvant therapy is not only to reduce the stage of shrinkage and increase the rate of surgical resection, but more importantly, to delay recurrence and prolong survival
.
The INCREASE study showed that nivolumab + ipimumab combined with neoadjuvant chemoradiotherapy enhanced the expression of CD4+ and CD8+ cells, subsets of memory cells in peripheral blood, and increased the expression of CD8+ T cell markers in tumor drainage lymph nodes
.
It is possible to mechanically elucidate the anti-tumor immune synergistic effect
of double-exemption combined with chemoradiotherapy and radiotherapy.

The safety profile of the INCREASE study was acceptable: no patients delayed surgery due to neoadjuvant therapy, no treatment-related deaths
.
With a 67% incidence of treatment-related grade 3-4 adverse events and 19% of immunotherapy-related grade 3-4 adverse events, it can be said that the addition of navurizumab + ipimumab did not significantly increase safety events
.

INCREASE study: More than half of the patients were PD-L1 expressing ≥ 50% (63%), T4 (66%), N0 (59%); The vast majority of patients received 2-cycle chemotherapy (89%), 2-cycle immunotherapy (93%), and 50Gy radiotherapy doses (88.
%)
.
The median interval between surgeries is 6 weeks (5 to 9 weeks)
after the end of neoadjuvant therapy.
These important parameters can provide a reference
for clinical practice.

In summary, the INCREASE findings suggest that neoadjuvanumab plus ipimumab combined with synchrotron chemoradiotherapy is safe and effective for the treatment of resectable or potentially resectable locally advanced non-small cell lung cancer, and is promising as a combination therapy model that doubles the rate of pathological remission with little increase in side effects, although longer follow-up and larger samples are needed to verify
.

References:

Ipilimumab plus nivolumab and chemoradiotherapy followed by surgery in patients with resectable and borderline resectable lung cancer: The INCREASE trial.
950O.
2022 ESMO.