Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer

Arafat Tfayli 1Majd Al Assaad 1Ghina Fakhri 1Reem Akel 1Hanine Atwi 1Hady Ghanem 2Fadi El Karak 3Fadi Farhat 4Kamal Al Rabi 5Pierre Sfeir 6Pierre Youssef 7Ziad Mansour 8Hazem Assi 1Mohamad Haidar 9Alain Abi Ghanem 9Ibrahim Khalifeh 10Fouad Boulos 10Ramy Mahfouz 10Bassem Youssef 11Youssef Zeidan 11Rachelle Bejjany 1Fadlo Khuri 1

Affiliations

1Division of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon.

2Department of Internal Medicine, Lebanese American University Medical Center-Rizk Hospital, Beirut, Lebanon.

3Department of Internal Medicine, Saint Joseph University, Beirut, Lebanon.

4Division of Hematology-Oncology, Hammoud Hospital University Medical Center, Saida, Lebanon.

5Department of Internal Medicine, King Hussien Cancer Center, Amman, Jordan.

6Division of Cardiothoracic Surgery, American University of Beirut Medical Center, Beirut, Lebanon.

7Division of Cardiothoracic Surgery, Hammoud Hospital University Medical Center, Saida, Lebanon.

8Division of Cardiothoracic Surgery, Geitaoui Medical Center, Beirut, Lebanon.

9Department of Radiology, American University of Beirut Medical Center, Beirut, Lebanon.

10Department of Pathology, American University of Beirut Medical Center, Beirut, Lebanon.

11Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon.

PMID: 32991781

 PMCID: PMC7666740

 DOI: 10.1002/cam4.3456

Free PMC article

Abstract

Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC. Patients received three cycles of neoadjuvant chemotherapy with four doses of avelumab every 2 weeks. Patients with squamous cell cancer received cisplatin or carboplatin on day 1 and gemcitabine on days 1 and 8 of each cycle of chemotherapy. Patients with nonsquamous histology received cisplatin or carboplatin with pemetrexed on day 1 of each cycle. Patients then proceeded to their planned surgery. Out of 15 patients accrued as part of stage 1 of the study, four had a radiologic response (1 complete response), lower than the minimum of six responses needed to continue to phase 2 of the study. The study was therefore terminated. Majority had adenocarcinoma histology and stage IIIA disease. The treatment was well tolerated with no unexpected side effects. Four patients (26.7%) had grade III/IV CTCAE toxicity. This study confirms that the preoperative administration of chemotherapy and avelumab is safe. There was no indication of increased surgical complications. The benefit of adding immunotherapy to chemotherapy did not appear to enhance the overall response rate of patients in the neoadjuvant setting in patients with resectable NSCLC because this study failed to meet its primary endpoint.

Keywords: immune checkpoint inhibitors; neoadjuvant therapy; nonsmall cell lung cancer; oncogenic drivers.

Conflict of interest statement

The authors declare no conflict of interest.