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

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.

SUBMITTER: Tfayli A

PROVIDER: S-EPMC7666740 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Tfayli Arafat A Al Assaad Majd M Fakhri Ghina G Akel Reem R Atwi Hanine H Ghanem Hady H El Karak Fadi F Farhat Fadi F Al Rabi Kamal K Sfeir Pierre P Youssef Pierre P Mansour Ziad Z Assi Hazem H Haidar Mohamad M Abi Ghanem Alain A Khalifeh Ibrahim I Boulos Fouad F Mahfouz Ramy R Youssef Bassem B Zeidan Youssef Y Bejjany Rachelle R Khuri Fadlo F

Cancer medicine 20200929 22

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 ...[more]

PMID: 32991781

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Project description:BackgroundNeoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.MethodsIn this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients.ResultsThe median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group.ConclusionsIn patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).

Project description:BackgroundResearches on programmed cell death (PD-1) as neoadjuvant immunotherapy for resectable non-small cell lung cancer is underway, which brings hope for individuals with the disease. However, a study dedicated to lung squamous cell carcinoma (LUSC) specifically has yet to be conducted. Now, data from our pilot prospective research neoadjuvant study provide new insights in the field of neoadjuvant regimen for LUSC.MethodsBetween June 2019 and July 2020, 37 adults with untreated, surgically resectable stage IIB-IIIB LUSC were enrolled into this prospective study. Patients received 2 cycles of pembrolizumab (2 mg/kg) with chemotherapy (albumin-bound paclitaxel 100 mg/m2 on days 1 and 8 + carboplatin AUC 5) via intravenous administration every 3 weeks, and underwent surgical treatment 3-4 weeks after the second cycle. The primary endpoint of the study was the tumor pathologic complete response (pCR) rate. The toxicity profile, tumor major pathological remission, complete resection rate, response rate, and operative and postoperative complications were also evaluated.ResultsThe postoperative pathological specimens of 17 (45.9%) patients suggested pCR. Neoadjuvant pembrolizumab with chemotherapy had an acceptable side-effect profile, and no patients withdrew from the study preoperatively due to disease progression or toxicity. A major pathological response occurred in 24 (64.9%) resected tumors. All tumors were completely resected (R0, 100%). According to the Response Evaluation Criteria in Solid Tumors (RESIST), a response was evaluated before surgery in 32 (86.5%) patients by computed tomography. Twenty-five (67.6%) patients underwent thoracoscopic surgery. No deaths or postoperative major complications requiring reoperation occurred. Recurrence or metastasis was found in 2 patients during follow-up of 2-14 months.ConclusionsThe early outcomes of pembrolizumab with chemotherapy in the neoadjuvant setting as a novel treatment for resectable stage IIB-IIIB LUSC showed a high pCR rate that has not been seen previously, as well as a high R0 resection rate and a low toxicity profile. The long-term efficacy of this novel treatment and the validity of the present findings should be confirmed with longer follow-up and prospective comparative trials.

Project description:BackgroundWe compared the real-world efficacy and safety of neoadjuvant chemoimmunotherapy to chemotherapy alone in patients with stage III non-small-cell lung cancer (NSCLC).Participants and methodsA total of 59 consecutive patients were finally selected and divided into two groups: the neoadjuvant chemotherapy group (n = 33) and the neoadjuvant chemoimmunotherapy group (n = 26). The primary endpoint was disease-free survival (DFS). The secondary endpoints were pathological response, clinical response, and adverse events. All patients were followed up to collect perioperative pathology and clinical data.ResultsThe objective response rate (ORR), pathological complete response (pCR), and major pathological response (MPR) were significantly higher in the neoadjuvant chemoimmunotherapy group than in the neoadjuvant chemotherapy group (73.1% vs. 45.5%, 34.6% vs. 3.0%, and 65.3% vs. 15.1%, respectively; P < 0.05). There was no statistically significant difference in disease-free survival between the neoadjuvant chemoimmunotherapy and neoadjuvant chemotherapy groups (P = 0.129). Patients in the neoadjuvant chemoimmunotherapy group had a higher rate of tumor regression than those in neoadjuvant chemotherapy group (37.0% [25 patients] vs. 29.0% [33 patients], P = 0.018). However, no discernible correlation between MPR achievement and the degree of tumor shrinkage was observed in either group (P > 0.05). The cumulative MPR rates were 42.3, 50, and 65.3% for 2, 3, and ≥ 4 cycles, respectively, in the neoadjuvant chemoimmunotherapy group and 9.1, 12.1, and 15.1% for ≤ 2, 3, and ≥ 4 cycles, respectively, in the neoadjuvant chemotherapy group. Moreover, No statistical difference was observed between the two groups regarding postoperative complications, resection range, operation time, surgical method, and extent of resection (P > 0.05). Although the incidence of grades III-IV adverse events was higher in the neoadjuvant chemotherapy group than in the neoadjuvant chemoimmunotherapy group (33.3% vs. 4.6%, P = 0.042), there was no significant difference in the incidence of adverse events between the two groups (64.6% vs. 83.6%, P = 0.072).ConclusionIn stage III NSCLC, neoadjuvant chemoimmunotherapy achieved higher pathological and clinical remission rates than chemotherapy alone, with compromising safety, making it an attractive choice for neoadjuvant therapy.

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

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

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