Aim: This study assessed whether cetuximab 500 mg/m(2) administered every 2 weeks (Q2W), when combined with chemotherapy as a first-line (1L) treatment, was noninferior to the approved dose (400 mg/m(2) followed by 250 mg/m(2) once weekly [Q1W]) for overall survival (OS) in adults with RAS wild-type metastatic colorectal cancer (mCRC). Methods: This pooled analysis included patients receiving 1L treatment with cetuximab Q1W or Q2W in combination with chemotherapy from post-authorisation studies with patient-level data available to the sponsor. Baseline characteristics were adjusted with a propensity score using inverse probability of treatment weighting (IPTW). Noninferiority in terms of OS was tested with a noninferiority margin for the hazard ratio (HR) of 1.25 using a Cox proportional hazards regression model. Secondary outcomes were progression-free survival (PFS), overall response rate (ORR) and rates of lung/liver metastases resection and serious adverse events. Results: OS time was noninferior in the Q2W cohort (n = 554) compared to the Q1W cohort (n = 763), with a HR after IPTW (95% confidence interval) of 0.827 (0.715-0.956) and median OS times of 24.7 (Q1W) and 27.9 (Q2W) months. There were no major differences in PFS (HR: 0.915 [0.804-1.042]). The odds ratios (ORs) after IPTW for ORR (1.292 [1.031-1.617]) and the rates of lung/liver metastases resection (1.419 [1.043-1.932]) favoured the Q2W regimen. No differences were noted in the occurrence rate of any SAE between groups; the OR after IPTW was 1.089 (0.858-1.382). Conclusions: The cetuximab Q2W regimen was noninferior to the Q1W regimen for OS in the 1L treatment of mCRC. (C) 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license

Background The multicenter, open-label, randomized, phase III EPIC study (EMR 062202-025) investigated cetuximab plus irinotecan versus irinotecan in patients with epidermal growth factor receptor-detectable metastatic colorectal cancer (mCRC) that progressed on first-line fluoropyrimidine- and oxaliplatin-based chemotherapy; we report the outcomes of patients with RAS-wild-type (wt) disease. Materials and Methods Available DNA samples from RAS-unselected patients (n = 1,164 of 1,298 [89.7%]) were reanalyzed for RAS mutations using beads, emulsion, amplification, and magnetics. Baseline characteristics, efficacy, safety, and poststudy therapy were assessed. RAS-wt status was defined as a mutated RAS allele frequency of <= 5%, with all relevant alleles being analyzable. Results Baseline characteristics were comparable between the groups (n = 452 patients with RAS-wt mCRC; cetuximab plus irinotecan n = 231, irinotecan n = 221) and between the RAS-wt and RAS-unselected populations. In the cetuximab plus irinotecan versus irinotecan arms, median overall survival was 12.3 versus 12.0 months, median progression-free survival (PFS) was 5.4 versus 2.6 months, and objective response rate (ORR) was 29.4% versus 5.0%, respectively. Quality of life (QoL) was improved in the cetuximab plus irinotecan arm. Serious adverse events occurred in 45.4% (cetuximab plus irinotecan) and 42.4% (irinotecan) of patients. In total, 47.1% of patients in the irinotecan arm received subsequent cetuximab therapy. Conclusion PFS, ORR, and QoL were improved with cetuximab plus irinotecan as a second-line treatment in patients with RAS-wt mCRC, confirming that cetuximab-based therapy is suitable in this population. Almost half of patients in the irinotecan arm received poststudy cetuximab, masking a potential overall survival benefit of cetuximab addition. Implications for Practice Cetuximab is approved for the treatment of RAS-wild-type metastatic colorectal cancer (mCRC). In this retrospective analysis of the phase III EPIC study (cetuximab plus irinotecan vs. irinotecan alone as second-line treatment in patients with RAS-unselected mCRC), the subgroup of patients with RAS-wild-type mCRC who received cetuximab plus irinotecan had improved progression-free survival, objective response rate, and quality of life compared with the RAS-unselected population. These findings suggest that cetuximab-based therapy is a suitable second-line treatment for patients with RAS-wild-type mCRC.

Background: The EXTREME regimen (chemotherapy [CT; cisplatin/carboplatin and 5-fluorouracil]) plus cetuximab is a standard-of-care first-line (1L) treatment for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), as supported by international guidelines. The phase III CHANGE-2 trial assessed the efficacy and safety of a modified CT regimen (with a reduced dose of both components) and cetuximab versus CT for the 1L treatment of Chinese patients with R/M SCCHN. Methods: Patients were randomised to receive up to six cycles of CT plus cetuximab followed by cetuximab maintenance until progressive disease or CT alone. The primary end-point was the progression-free survival (PFS) time assessed by the independent review committee (IRC). Results: Overall, 243 patients were randomised (164 to CT plus cetuximab; 79 to CT). The hazard ratios for PFS by IRC and overall survival (OS) were 0.57 (95% CI: 0.40-0.80; median: 5.5 versus 4.2 months) and 0.69 (95% CI: 0.50-0.93; median: 11.1 versus 8.9 months), respectively, in favour of CT plus cetuximab. The objective response rates (ORR) by IRC were 50.0% and 26.6% with CT plus cetuximab and CT treatment, respectively. Treatment emergent adverse events of maximum grade 3 or 4 occurred in 61.3% (CT plus cetuximab) and 48.7% (CT) of patients. Conclusions: CHANGE-2 showed an improved median PFS, median OS and ORR with the addition of cetuximab to a modified platinum/5-fluorouracil regimen, with no new or unexpected safety findings, thereby confirming CT plus cetuximab as an effective and safe 1L treatment for Chinese patients with R/M SCCHN. Clinical trial registration number: NCT02383966. 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

AIM:The open-label, nonrandomized, phase II APEC study enrolled 167 patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) to investigate the safety and efficacy of first-line, every-2-weeks cetuximab plus investigator's choice of FOLFIRI or FOLFOX in this patient population.METHODS:A subgroup analysis of the APEC study population by primary tumor location was performed.RESULTS:A total of 130 patients (81.8%) had left-sided and 29 (18.2%) had right-sided mCRC. Median progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) were 14.0 months, 30.6 months and 68.5% for patients with left-sided tumors and 8.9 months, 24.6 months and 51.7% for patients with right-sided mCRC, concurring with pivotal phase III trial results. In patients with right-sided tumors, median PFS was 15.4 months vs 8.3 months with cetuximab plus FOLFIRI vs cetuximab plus FOLFOX, respectively; median OS was 32.1 months vs 21.8 months with cetuximab plus FOLFIRI vs cetuximab plus FOLFOX, respectively.CONCLUSION:The APEC tumor-location subgroup analysis results were largely consistent with available literature regarding the equivalent efficacy of cetuximab plus FOLFIRI/FOLFOX in patients with left-sided RAS wt mCRC. A trend toward improved efficacy with cetuximab plus FOLFIRI compared with cetuximab plus FOLFOX was observed in patients with right-sided tumors; however, a direct comparison between groups cannot be made due to the nonrandomized study design. Nevertheless, the similar ORR observed with either chemotherapy backbone in patients with right-sided RAS wt mCRC suggests a potential role for both regimens in this patient population when cytoreduction is a treatment goal.

Background Cetuximab (CET) in combination with chemotherapy is approved for a once-weekly (q1w) schedule at an initial dose of 400 mg/m², followed by weekly doses of 250 mg/m², in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC). However in clinical practice, an off-label schedule of CET 500 mg/m2 every-2-weeks (q2w) is frequently used. This pooled analysis of patient-level data aimed to test the noninferiority of the q2w vs q1w schedule on overall survival (OS). Methods All post-authorization studies with patient-level data available to marketing authorization holder at time of study design, in patients with confirmed RAS wt mCRC who received a first-line treatment with CET q1w or q2w in combination with chemotherapy from 2007 to 2018 were included: 2 non-interventional cohort studies (NIS) (EREBUS, ERBITAG) and 3 clinical trials (CEBIFOX, CECOG/CORE 1.2.002, APEC). Patients were categorized into q1w or q2w groups according to the CET schedule planned at initiation. OS was calculated from first CET infusion until all-cause death and censored at the last date patients were known to be alive. The noninferiority of the q2w vs q1w schedule was tested with a hazard ratio (HR) margin of 1.25 using a Cox proportional hazards regression model. Differences in baseline characteristics were accounted for with inverse probability of treatment weighting (IPTW) based on a propensity score. Results 763 (91% from NIS) and 554 (51% from NIS) patients were included in the q1w and q2w groups, respectively. Median (Q1-Q3) age in years was 66 (57-73) for q1w and 60 (53-69) for q2w. Liver-limited disease concerned 42.6% of patients for q1w and 37.9% for q2w. A baseline ECOG Performance Status of 0-1 was reported in 81.8% of q1w and 90.6% of q2w patients. FOLFIRI was most frequently used in combination with q1w (49.4%) and FOLFOX with q2w (59.2%). IPTW-adjusted HRs for OS were in favor of q2w: 0.83 (95% CI, 0.71-0.96) and 0.73 (95% CI, 0.61-0.88) when restricted to NIS. Other efficacy and safety results will be presented in the future. Conclusions This pooled analysis confirmed the noninferiority of CET q2w vs q1w. This result suggests an improved OS with the q2w schedule. Editorial acknowledgement ClinicalThinking, Inc, Hamilton, NJ, USA, funded by Merck Healthcare KGaA, Darmstadt, Germany. Legal entity responsible for the study Merck Healthcare KGaA. Funding Merck Healthcare KGaA. Disclosure S. Kasper: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Aventis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly. F. Overkamp: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Chugai; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Cellex; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Gilead; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Novonordisc; Honoraria (self), Advisory / Consultancy: Riemser; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Servier. C. Foch: Full / Part-time employment: Merck Healthcare KGaA. F. Lamy: Full / Part-time employment: Merck Healthcare KGaA. R. Esser: Full / Part-time employment: Merck Healthcare KGaA. D. Messinger: Full / Part-time employment, Prometris provides statistical services for Merck Healthcare KGaA: Merck Healthcare KGaA. V. Rothe: Full / Part-time employment, Prometris provides statistical services for Merck Healthcare KGaA: Merck Healthcare KGaA. W. Chen: Full / Part-time employment: Merck Serono. T. Brodowicz: Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: PharmaMar; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Lilly. C.C. Zielinski: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Imugene; Honoraria (self), Advisory / Consultancy: ARIAD; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Merrimack; Honoraria (self), Advisory / Consultancy: Merck Healthcare KGaA; Honoraria (self), Advisory / Consultancy: FibroGen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Gilead; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy: Shire; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Athenex. All other authors have declared no conflicts of interest.

3580 Background: The multicenter, open-label, randomized, phase 3 EPIC study (EMR 062202-025) investigated cetuximab + irinotecan vs irinotecan as a second-line (2L) therapy in pts with EGFR-detectable mCRC. A retrospective analysis in the EPIC RAS wt population showed improved overall response rate (29.4% vs 5.0%) and progression-free survival (5.4 vs 2.6 mo) upon the addition of cetuximab to irinotecan. Median OS (mOS) was similar in both treatment arms, possibly due to differences in subsequent therapies. We present OS by post-study therapy in the RAS wt population. Methods: 1298 RAS-unselected pts were enrolled from May 2003 to February 2006. The primary endpoint was OS. RAS status was determined retrospectively in 2018 from existing DNA samples using BEAMing technology; wt status was defined as having a sum of mutated RAS allele frequencies of ≤5%, with all relevant alleles being analyzable. Results: Among the 452 pts with RAS wt mCRC, 231 received cetuximab + irinotecan and 221 received irinotecan. Baseline characteristics were similar in both arms. OS data by post-study therapy are summarized in the Table. No new or unexpected safety signals were observed. Conclusions: Post-study cetuximab was associated with improved OS in both treatment arms compared with post-study therapy without cetuximab and no subsequent therapy, suggesting that cetuximab-based therapy may be suitable as a standard treatment for pts with RAS wt mCRC in the rechallenge setting. Study limitations include a potential bias due to the differences in proportion of subsequent therapies with and without cetuximab between arms (almost 50% of pts in the irinotecan arm received post-study cetuximab) as well as the likelihood for pts who live longer to receive cetuximab in any subsequent therapy line. [Table: see text]

3521 Background: The survival advantage conferred by the addition of cet to FOLFOX chemotherapy was verified in TAILOR, the first prospective, randomized, phase 3 study of the addition of cet to 1L FOLFOX in pts with RAS wt mCRC. We previously presented the primary analysis of the TAILOR trial, with fewer OS events. Here, we provide the final OS results for this trial. Methods: TAILOR was an open-label, randomized, multicenter, phase 3 trial with a modified intention-to-treat (mITT) population of 393 pts from China that evaluated FOLFOX-4 ± cet in RAS wt mCRC. The primary endpoint was progression-free survival (PFS) time; secondary endpoints include OS time, overall response rate (ORR), and safety/tolerability. Results: An updated analysis (performed after 84% of events occurred) verified the survival advantage of the addition of cet to FOLFOX-4 (Table). Additionally, > 77% of pts in the cet + FOLFOX-4 arm reached ≥ 80% dose intensity of cet, confirming that cet + FOLFOX-4 has high compliance. There were no new or unexpected safety findings. Finally, 59.6% and 56.0% of pts in the cet + FOLFOX-4 and FOLFOX-4 arms, respectively, received subsequent anticancer therapy after treatment discontinuation (54.4% and 49.5% received any chemotherapy, and 17.6% and 27.0% received any targeted therapy). Clinical trial information: NCT01228734. Conclusions: The TAILOR study met all its endpoints, confirming cet in combination with FOLFOX-4 as an effective standard-of-care 1L treatment regimen for pts with RAS wt mCRC. We acknowledge that OS findings for the mITT population are likely influenced by the low percentage of pts who received further lines of treatment after progression on their 1L regimen, suggesting regional differences in access to anticancer therapy. Efficacy outcome Cet + FOLFOX-4 (n = 193) FOLFOX-4 (n = 200) OS # events 156 174 Median, months 20.8 16.5 95% CI 16.3-23.5 14.8-19.5 HR (95% CI); p value 0.763 (0.614-0.949); p = .015 PFS by investigator # events 165 142 Median, months 9.2 7.4 95% CI 8.8-10.9 5.8-7.5 HR (95% CI); p value 0.629 (0.498-0.794); p < .001 Response rate by investigator, % ORR 66.3 40.5 95% CI 59.2-72.9 33.6-47.7 OR (95% CI); p value 2.893 (1.918-4.363); p < .001

747 Background: In the RAS wt population of APEC, q2w cetuximab combined with 1L FOLFOX or FOLFIRI achieved a best confirmed overall response rate (BORR), median progression-free survival (PFS), and median overall survival (OS) similar to those reported in prior 1L pivotal studies involving weekly (qw) cetuximab. In this hypothesis-generating subgroup analysis, we evaluated the impact of TS in APEC study patients with RAS wt mCRC. Methods: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region, with BORR as the primary endpoint. Patients with KRAS exon 2 wt tumors received q2w cetuximab + investigator’s choice of FOLFOX or FOLFIRI; subsequent analyses considered patients who were RAS wt ( KRAS/ NRAS, exons 2-4). TS was categorized in evaluable patients with RAS wt tumors (left [L]-sided = splenic flexure, descending colon, sigmoid colon, and rectum; right [R]-sided = appendix, cecum, ascending colon, hepatic flexure, and transverse colon). Results: Among 167 patients with RAS wt mCRC, 159 were evaluable for TS; 130 (81.8%) had L-sided and 29 (18.2%) had R-sided mCRC. Baseline characteristics in the TS subgroups reflected the known differences between L- and R-sided mCRC. Efficacy data for the TS subgroups are summarized in the table. Conclusions: Consistent with prior 1L pivotal studies involving qw cetuximab, a prognostic effect of TS in patients receiving 1L q2w cetuximab was confirmed in APEC. BORR remained ≥50% in patients with R-sided mCRC, in line with prior evidence that use of cetuximab may be appropriate when tumor shrinkage/cytoreduction is the goal. These hypothesis-generating data also raise the possibility of synergy between cetuximab and, in particular, irinotecan for PFS and OS in patients with R-sided tumors, although numbers are small. Clinical trial information: NCT00778830. [Table: see text]

3534 Background: In the RAS wt population of APEC, q2w cetuximab combined with first-line FOLFOX or FOLFIRI achieved an overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) similar to those reported in prior first-line pivotal studies involving weekly cetuximab. In this subgroup analysis, we evaluated the impact of tumor side in the APEC study population with RAS wt mCRC. Methods: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region, with ORR as the primary endpoint. Patients with KRAS exon 2 wt tumors received q2w cetuximab + investigator’s choice of FOLFOX or FOLFIRI. Tumor side was categorized in evaluable patients with RAS wt tumors (left [L]-sided = splenic flexure, descending colon, sigmoid colon, and rectum; right [R]-sided = appendix, cecum, ascending colon, hepatic flexure, and transverse colon). Results: Among 167 patients with RAS wt mCRC, 159 were evaluable for tumor side; 130 (81.8%) had L-sided and 29 (18.2%) had R-sided mCRC. Baseline characteristics in the tumor side subgroups reflected the known differences between L- and R-sided mCRC; indeed, 95.4% and 75.9% of patients had BRAF wt disease, respectively. Efficacy data are summarized in the Table. Conclusions: Consistent with prior first-line pivotal studies with weekly cetuximab, a prognostic effect of tumor side in patients receiving first-line q2w cetuximab was confirmed in APEC. In patients with R-sided mCRC, ORR remained ≥ 50%, and resection rate was comparable to that of L-sided patients, in line with prior evidence showing that use of cetuximab may be appropriate when rapid tumor shrinkage is the goal. These hypothesis-generating data raise the possibility of a synergy between cetuximab and irinotecan in patients with R-sided tumors, although numbers are small. Clinical trial information: NCT00778830. L-side R-side Cetuximab + FOLFIRI Cetuximab + FOLFOX Total Cetuximab + FOLFIRI Cetuximab + FOLFOX Total n 43 87 130 10 19 29 ORR, % 74.4 65.5 68.5 50.0 52.6 51.7 Median PFS, months 12.8 14.2 14.0 15.4 8.3 8.9 Median OS, months 31.7 30.6 30.6 32.1 21.8 24.6 Resection rate, % 2.3 14.9 10.8 10.0 10.5 10.3

8547 Background: Patients (pts) with NSCLC that is initially responsive to EGFR tyrosine kinase inhibitors (EGFR TKI) typically develop resistance, often associated with aberrant c-Met activity. Dual inhibition of EGFR and c-Met is therefore a rational option to treat c-Met+ EGFR TKI-resistant NSCLC. Tepotinib is a highly selective c-Met inhibitor with good tolerability and promising activity against solid tumors. We report final data from a phase Ib trial of tepotinib + gefitinib in pts with c-Met+/EGFR-mutant NSCLC conducted in Asia. Methods: Eligible pts were adults with locally advanced/metastatic NSCLC and ECOG PS 0–1. Tumors had to express EGFR with an activating mutation be resistant to EGFR TKI therapy and be c-Met+ by IHC. Pts received tepotinib 300 or 500 mg QD combined with gefitinib 250 mg QD (T300G250 or T500G250). The primary objective was to determine the recommended phase II dose (RP2D) of tepotinib in combination with gefitinib; secondary objectives included pharmacokinetics (PK), safety, and antitumor activity. Results: 18 pts were enrolled (median age 65 [41–78]; 8 male); 6 received T300G250, 12 T500G250. No dose-limiting toxicities were observed, and tepotinib 500 mg QD was confirmed as the RP2D. 17 pts experienced treatment-related treatment-emergent adverse events (TRTEAEs), mostly grade ≤2 and most commonly diarrhea (12), rash (8), and amylase increase (6). Grade ≥3 TRTEAEs were increased amylase (n = 4), increased lipase (3), neutropenia (1), and hyperglycemia (1). The best overall response was partial response in 6 pts; 4/7 pts with IHC 3+ tumors responded (all treated with T500G250) vs 2/11 with IHC 2+ tumors. Response durations of pts with PR were 4.2–12.5 months. 4/18 pts (IHC 2+, n = 3) had stable disease. 8 pts experienced progression free survival > 5 months, 3 pts > 10 months. PK were as expected from previous studies. Conclusions: Tepotinib in combination with gefitinib was well tolerated. The RP2D of tepotinib for use in combination with gefitinib in NSCLC is 500 mg QD. T500G250 showed signs of activity against c-Met+ tumors. A phase II trial is randomizing ≈156 pts with c-Met+/T790M– tumors who have failed first-line EFGR TKI 2:1 to tepotinib + gefitinib or pemetrexed + cisplatin/carboplatin. Clinical trial information: NCT02864992.

Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in regulating the immune response against cancer. This study investigated the prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating immune cells (TILs) in the tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma (ESCC). Archival formalin-fixed, paraffin-embedded ESCC samples from treatment-naïve patients with ESCC after surgery or by diagnostic endoscopic biopsy were collected between 2004 and 2014. Expression of PD-L1 in ESCC tumor specimens was assessed by immunohistochemistry (IHC), and the degree of TIL infiltration was evaluated by examining hematoxylin and eosin-stained (H&E) specimens. PD-L1+ as defined as ≥1% of tumor cell membranes showing ≥1+ intensity. In 428 patients, specimens from 341 (79.7%) were PD-L1+. In the definitive treatment group (patients who received curative esophagectomy or definitive [chemo-]radiation therapy), PD-L1 positivity was associated with a significantly shorter DFS and OS. In the palliative chemotherapy group exhibited, neither PFS nor OS correlated significantly with PD-L1 expression. PD-L1 expression was positively associated with TIL density. In 17 paired tumor tissues collected before and after treatment, an increase in PD-L1 expression was associated with disease progression, whereas a decrease in PD-L1 expression was associated with response to chemotherapy or disease control. So, PD-L1 expression was associated with a significantly worse prognosis in patients with ESCC. These observations suggest that PD-L1 may play a critical role in ESCC cancer progression and provide a rationale for developing PD-L1 inhibitors for treatment of a subset of ESCC patients.

683 Background: In the RAS wt population of TAILOR, adding cet to 1L F significantly improved progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). In this subgroup analysis, we evaluate the impact of TL. Methods: TAILOR is a randomized phase 3 trial that includes a modified intention-to-treat (mITT) population of 393 pts from China with RASwt mCRC treated with F ± cet. The primary endpoint of TAILOR is PFS; key secondary endpoints include OS and ORR. TL was categorized in evaluable pts in the mITT population (left-sided = splenic flexure, descending colon, sigmoid colon, and rectum; right-sided = appendix, cecum, ascending colon, hepatic flexure, ± transverse colon). Results: Efficacy data for the TL subgroups are summarized in the table. Additionally, the prognostic effect of TL (left- vs right-sided) within the treatment arms could be shown for PFS (HR = 1.72; p = .007), OS (HR = 1.84; p = .002), and ORR (OR = 0.40; p = .014) in the cet + F arm and PFS (HR = 1.97; p = .002), OS (HR = 1.43; p = .073), and ORR (OR = 0.41; p = .028) in the F arm. Regarding the potential predictive value of TL, the p values for the interaction between TL and treatment are: PFS (.676), OS (.339), and ORR (.986). Conclusions: In TAILOR, adding cet to 1L F clearly benefitted RAS wt pts with left-sided tumors in terms of PFS, OS, and ORR; for pts with right-sided tumors, the HRs for PFS and the ORs for ORR also consistently suggested a benefit showing a trend in favor of cet. Clinical trial information: NCT01228734. [Table: see text]

The purpose of the present study is to explore the influence of body mass index (BMI) on outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) techniques in Chinese women with polycystic ovary syndrome (PCOS).

4072 Background: Patients (pts) with advanced HCC have a poor prognosis, particularly if tumor c-Met activity is aberrant. Current first-line therapy is sorafenib, which has limited efficacy and is not widely used in Asia. Tepotinib (MSC2156119J) is a highly selective c-Met inhibitor with favorable safety and promising antitumor activity, particularly in c-Met+ tumors. Translational modeling established a recommended phase II dose (RP2D) of 500 mg/day. All patients enrolled into a phase Ib trial of tepotinib in Asian pts with HCC have completed the dose-limiting toxicity (DLT) evaluation period and data are reported. Methods: Asian adults with confirmed HCC of BCLC Stage C, Child-Pugh Class A liver function without encephalopathy, and ECOG PS 0–2 were recruited to this 3+3 dose-escalation study (tepotinib 300 or 500 mg/day, 21-day cycle; protocol amendment added a 1,000 mg/day cohort, n = 6). In total, 12 patients were to be enrolled at the RP2D. c-Met expression was retrospectively determined by IHC. PK was analyzed by non-compartmental methods. Results: 27 pts were enrolled (median age 57 [38-69]; male 23; ECOG PS 0/1 11/15). 7 received tepotinib 300 mg/day, 14 500 mg/day, and 6 1,000 mg/day. No DLTs were observed. 22 pts experienced treatment-related treatment-emergent adverse events (TRTEAEs); most were grade ≤ 2. The most common TRTEAEs were diarrhea (n = 10), elevated AST (7), nausea (7), and elevated ALT (6). 15 grade ≥ 3 TRTEAEs occurred, including grade 3 increased lipase levels (n = 3) and grade 3 diarrhea (n = 2). Best overall response (BOR) in pts with c-Met+ (n = 7) tumors was partial response (n = 2), stable disease (SD; n = 2), and progressive disease (PD; n = 3). The 2 pts with PRs were treated with tepotinib 500 and 1,000 mg/day, respectively; AFP levels in these pts were at least stabilized during response to tepotinib. Of 18 pts with c-Met– tumors, 6 had a BOR of SD, 10 PD, and 2 were not evaluable. Conclusions: Data indicate that tepotinib at doses of up to 1,000 mg/day is well tolerated by Asian pts with HCC. Efficacy appeared to be greatest in the c-Met+ population. The ongoing phase II part of this study is comparing the efficacy and safety of first-line tepotinib and sorafenib in pts with c-Met+ HCC. Clinical trial information: NCT01988493.