e21056 Background: High risk cutaneous squamous cell cancer of the head and neck (cSCC-HN) have suboptimal outcomes with surgery and postoperative radiation. We report preliminary safety outcomes of a phase II study (NCT03057613) exploring the safety and efficacy of the addition of Pembrolizumab to postoperative IMRT. Methods: Patients with cSCC-HN were eligible for this IRB approved study if they had resection of all gross disease and demonstrated (a) invasion of the skeleton or skull base; (b) node positive disease; (c) or a tumor > 2cm with ≥1 of the following risk factors: recurrent disease, perineural invasion, lymphovascular space invasion, poorly differentiated, positive margins, satellitosis or in-transit metastases. Immune competent pts and those with CLL were eligible. This study aimed to accrue 34 evaluable patients to assess a primary safety endpoint of dose limiting toxicity (DLT) defined as any grade ≥3 toxicity at least possibly related to the immunotherapy. Assuming toxicity of < 20% is acceptable and > 40% is unacceptable, if ≥11 of 34 (32%) patients experienced a DLT, the regimen would be considered unsafe. Results: Of 15 pts already enrolled on this study, 11 have completed the protocol treatment. There were no DLTs observed to date. Grade 2 immune related toxicity was seen in two patients, one with bullous pemphigoid and another with lymphopenia and peripheral neuropathy and weakness in his hands in the setting of a prior cervical spine injury. Both responded to steroids and recovered completely. Based on this initial cohort, the 95% confidence intervals (CI) on DLTs for the entire cohort is 0-28%. Using the most conservative CI of 28%, the likelihood of 11 of the remaining 23 patients experiencing a DLT is 3.4%. Assuming a CI of 20%, the risk is 0.3%. None of the 11 pts who have completed protocol therapy have experienced a recurrence. Conclusions: The addition of Pembrolizumab to postoperative IMRT in high risk cSCC-HN is safe and will be studied in a randomized phase III adjuvant study (Keynote 630). This phase II study will continue to enroll CLL patients to assess safety and efficacy signals in this unique higher risk population. Clinical trial information: NCT03057613.
No abstract
7557 Background: Concurrent chemoradiotherapy (CRT) is standard treatment for stage III NSCLC, although the management of resectable patients (pts) remains controversial. We report an open-label phase I/II trial of the epidermal growth factor receptor inhibitor E added to perioperative CRT for resectable stage III NSCLC pts, followed by maintenance (m) E. Methods: Eligible pts had stage IIIA/B NSCLC, PS 0–1, and were resectable as determined by a thoracic surgeon. Pts received weekly P (50 mg/m2), and C (AUC 2) with daily oral E for 28 days concurrent with twice daily thoracic radiation (1.5 Gy/fraction) to 30 Gy, followed by restaging. Non-progressors underwent resection followed by the same CRT regimen and 2 years of mE (150mg). The primary endpoint of the phase I portion was the maximum tolerated dose (MTD) of E given with CRT; and for the phase II was safety and tolerability. Secondary endpoints were pathologic complete response (pCR) rate, pathologic downstaging of mediastinal nodes, progression free survival (PFS), and overall survival (OS). Results: 9 pts were enrolled in the phase I trial. The MTD of E was150mg, which was the phase II dose used. 25 pts were treated in the phase II component: median age 60, 92% stage IIIA, 64% female, 72% PS 0, 64% adenocarcinoma, and 16% never smokers. The median duration of mE was 5.5 months, with the most common reason for discontinuation being pt preference. There was no grade 4 toxicity. Grade 3 toxicity seen in >5% of pts: rash (12%), diarrhea (9%), nausea (9%), and encephalopathy (6%). The most common toxicities during mE: grade 1/2 diarrhea (72%), rash (61%), fatigue (56%), nausea (22%), and dry eyes (17%).1 pt (4%) had a pCR after neoadjuvant CRT, and 46% were downstaged to pN0–1 at surgery. At a median follow-up of 36.5 mos the median PFS is 41.8 mos (95% CI 9.3-not yet reached). The median OS has not been reached. 3 year survival is 69%. Pts downstaged to pN0–1 vs those with persistent pN2–3 had a median PFS of 41.8 vs 18.1 mos (p=0.11). Conclusions: Perioperative P, C, and E given concurrently with HFRT was well tolerated and showed promising efficacy, while compliance was poor with maintenance E. [Table: see text]
e18085 Background: The ALK 2p23 translocation, ALK(+), is an important druggable target in 5-7% of non-small cell lung cancer (NSCLC). However, the break-part FISH assay is labor-intensive. Better understanding of the target population’s clinical features and alternative screening tests are desirable to enable cost-effective patient selection for molecular therapy. Methods: NSCLC patients (N=120) seen at the Cleveland Clinic (CC) who had clinical screening ALK 2p23 FISH (Abbott Molecular) were included in this retrospective analysis. Biopsy specimens were also tested using immunohistochemistry (IHC) for ALK overexpression via clone D5F3 (Cell Signaling Tech.) with OptiView ultrasensitive detection (Ventana Medical Sys.). Clinical data were extracted from electronic medical records. Comparison was performed using Fisher’s exact test, Wilcoxon rank sum test or log-rank test. Results: Of the 120 tumors tested, 34 (28.3%) were ALK(+) by FISH, predominantly adenocarcinomas (33/34). 97% of the samples were also tested by ALK-IHC, with a concordance rate of 99%. Comparing to ALK (-) group, ALK(+) patients were younger (median 53 vs 65, p<0.01) and mostly never/light smokers (91% vs 43%, p<0.01). ALK(+) tumors tended to have higher number of metastatic sites at diagnosis, especially for liver metastasis (26.5% vs 10.5%, p=0.04). Interestingly, venous thrombosis (DVT/PE) was also significantly more common in ALK(+) patients (35.3% vs 16.3%, p=0.03). 17 (50%) patients were treated with crizotinib in the ALK(+) group. Two cases with positive screening ALK-IHC helped to identify FISH(+) tumor areas. Of those tumors with EGFR status available (n=103), 6 were EGFR mutation-positive, all being ALK(-). No significant OS difference was seen in ALK(+)/EGFR(-) patients (n=28) compared to ALK(-)/EGFR(-) patients (n=69). Conclusions: ALK 2p23 (+) NSCLC at CC was more commonly seen in younger patients and never/light smokers. They tended to have greater number of metastases, especially in the liver, and significantly higher risk of venous thrombosis. ALK-ultrasensitive IHC using the D5F4 clone helped to identify FISH(+) tumor areas and may be considered a cost-effective screening test demonstrating high concordance with ALK FISH.
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