P3.01-19 Sequencing of Ramucirumab+Docetaxel Post-Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer Patients

Abstract

Background: The anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors, nivolumab and pembrolizumab, are currently approved for the treatment of patients with NSCLC. The PD-L1 expression represents the most validated predictive marker of response to PD-1 inhibitors. However, there are several different immunohistochemical assays to assess the PD-L1 expression using different antibodies, platforms, and cutoff values. We compared the PD-L1 expression evaluated by IHC 22C3 PharmDx with that observed by Ventana SP263 and analyzed correlation with response to anti PD-1 inhibitors. Method: We retrospectively analyzed 109 patients with lung cancer to be treated with anti PD-1 inhibitors who have PD-L1 expression levels obtained with both the 22C3 and SP263 assays. We reviewed medical records to obtain information about the patient's clinical characteristics, response evaluation and survival data. The relationship between PD-L1 expression levels evaluated by the 22C3 and SP263 assays was calculated using the concordance correlation coefficient, Pearson's precision analysis. Result: Most patients were male (70%), smoker (65%), ECOG PS 1 (73%), and histologically adenocarcinoma (55%) or squamous cell carcinoma (29%). 30% of patients had EGFR mutations. Patients were treated with pembrolizumab (n¼41, 38%), or nivolumab (n¼67, 61%). The median cycle of anti PD-1 checkpoint inhibitor was three (range, 1-25). There was moderate analytical correlation between 22C3 and SP263 PD-L1 levels. At the clinically relevant cutoffs ( < 10% vs. 10%; and <1% vs. 1-49% vs. 50%), the concordance correlation coefficient between 22C3 and SP263 were 0.68 (95%CI: 0.59-0.77) and 0.66 (95%CI: 0.51-0.81), respectively. The overall response rate (ORR) was 25.0% for all patients. The ORR was comparable regardless of the cutoff levels of PD-L1 expression by SP263 assays (ORR 39.6%, 41.7%, and 47.4% respectively for PD-L1 expression by 1%, 10%, 50% cutoff levels). But, the correlation between ORR and PD-L1 expression by 22C3 assays was not statistically significant. At 1% cutoff value, progression free survival was longer in patients with high vs. low tumor PD-L1 expression (2.8 months vs. 1.2 months, HR 0.63, 95% CI: 0.41-0.97, p¼0.03) by the 22C3 and (3.1 months vs. 1.3 months, HR 0.61, 95% CI:0.40-0.93, p¼0.02) by the SP263, respectively. Conclusion: We showed a moderate correlation between PD-L1 expression data obtained with the 22C3 and SP263 assays. These two assays could be used interchangeably and might be helpful for decision with anti PD-1 checkpoint inhibitors. Further analysis will be updated. Background:The Phase III REVEL study demonstrated the efficacy and safety of ramucirumab+docetaxel (ram+doc) in advanced nonsmall cell lung cancer (aNSCLC) patients who had disease progression on prior platinum-based chemotherapy (chemo). Given recent positive data disclosures supporting the use of chemo+immune checkpoint inhibitor (ICI) combinations in frontline, there is a need for additional data on the sequencing of ram+doc post-ICIs. Me...

Exploratory analysis of front-line therapies in REVEL: a randomised phase 3 study of ramucirumab plus docetaxel versus docetaxel for the treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy

“…However, based on what is known regarding mechanism of action, the efficacy and safety profile for ramucirumab plus docetaxel following both immunotherapy and chemotherapy in the first line is expected to be consistent with what was observed in REVEL. There are ongoing efforts to use real-world evidence to evaluate outcomes for ramucirumab plus docetaxel in the postimmunotherapy setting,32 33 and additional studies are needed to specifically evaluate outcomes for ramucirumab plus docetaxel following immuno-oncology and chemotherapy combinations in the first line.…”

Clinical outcomes of ramucirumab plus docetaxel in the treatment of patients with non-small cell lung cancer after immunotherapy: a systematic literature review

“…Moreover, a statistically significant improvement in real-world DCR was observed when compared to ramucirumab plus docetaxel given after other non–ICIs (80.7% vs 54.4%; P <0.01) ( 45 ). Furthermore, in a cohort of patients treated with third-line ramucirumab plus docetaxel after ICI treatment, median real-world PFS (measured from the start of third-line ramucirumab plus docetaxel) was 3.6 months (range: 3.0-4.6 months) while median real-world OS (measured from the start of first-line therapy) was 19 months (range: 15.7-23.7 months) ( 47 ). The TREAT-LUNG study, a large retrospective observational study that collected data from 3 electronic health record-derived databases, investigated efficacy outcomes of second- or third-line therapy with ramucirumab plus docetaxel administered after prior chemotherapy plus ICIs.…”

“…A total of 11 studies were excluded from the efficacy analysis because they did not meet the inclusion criteria. However, results from these excluded studies also indicated that ramucirumab plus docetaxel was a safe and efficacious treatment after prior treatment with ICIs (35,37,42,(45)(46)(47)(67)(68)(69)(70). Five of these were real-world studies that used electronic health record-derived databases were not included in the efficacy analysis because they did not meet the SLR inclusion criteria (45)(46)(47)71) or they had a high percentage of missing data (e.g., tumor response assessment) and therefore had a high potential for misclassification and residual confounding bias (72).…”

“…However, results from these excluded studies also indicated that ramucirumab plus docetaxel was a safe and efficacious treatment after prior treatment with ICIs (35,37,42,(45)(46)(47)(67)(68)(69)(70). Five of these were real-world studies that used electronic health record-derived databases were not included in the efficacy analysis because they did not meet the SLR inclusion criteria (45)(46)(47)71) or they had a high percentage of missing data (e.g., tumor response assessment) and therefore had a high potential for misclassification and residual confounding bias (72). However, results from most of these studies suggest a trend towards improved efficacy outcomes with ramucirumab plus docetaxel administered after ICIs.…”

“…Randomized controlled studies investigating the efficacy and safety of ramucirumab plus docetaxel in the post-immunotherapy setting are lacking. Nevertheless, the efficacy and safety of ramucirumab plus docetaxel in patients previously treated with ICIs have been reported in recent years, mostly from retrospective observational studies (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44) and electronic health record studies (45)(46)(47). We conducted a systematic literature review (SLR) to consolidate the available evidence on the efficacy and safety of ramucirumab plus docetaxel when administered to patients with metastatic NSCLC previously treated with ICIs.…”