Safety and Efficacy of Cetuximab-Based Salvage Chemotherapy After Checkpoint Inhibitors in Head and Neck Cancer.

BACKGROUND: There are still few data on the activity and safety of cetuximab-based salvage chemotherapy after immunotherapy (SCAI) in patients with squamous cell cancer of the head and neck (SCCHN). MATERIALS AND METHODS: This was a retrospective study of patients with SCCHN who received cetuximab-based SCAI after programmed cell death protein 1 or programmed cell death ligand 1(PD[L]1) inhibitors. Overall response rate (ORR) and disease control rate (DCR) with SCAI and with last chemotherapy before immunotherapy (LCBI) by RECIST 1.1, percentage change from baseline in target lesions (PCTL), progression-free survival (PFS), overall survival (OS), treatment compliance, and toxicity were evaluated. RESULTS: Between March 2016 and November 2019, 23 patients were identified. SCAI consisted of cetuximab-based combinations (3-weekly cisplatin-5FU-cetuximab [n = 2], weekly paclitaxel-cetuximab [n = 17], weekly cisplatin-cetuximab [n = 2], weekly carboplatin-paclitaxel-cetuximab [n = 2]). ORR was 56.5% (11 partial response, 2 complete response). DCR was 78.3%. Among 13 objective responders, median best PCTL was -53.5% (range, -30% to -100%). Median OS and PFS were 12 months and 6 months, respectively. In 10 patients receiving LCBI, ORR to LCBI was 40%, whereas ORR to SCAI achieved 60%. In LCBI-treated patients, median PFS with LCBI was 8 months and median PFS and OS with SCAI were 7 months and 12 months, respectively. Reduced dose intensity of the chemotherapy and cetuximab components occurred in 82.6% and 52.2% of the patients. Grade 1 or 2 adverse events (AEs) occurred in all patients. Grade 3 or 4 AEs developed in 65%, being grade 3 in all of them except in one patient (grade 4 neutropenia). There were no treatment-related deaths. CONCLUSION: Cetuximab-based salvage chemotherapy after PD(L)1 inhibitors associated with high response rates and deep tumor reductions with a manageable safety profile. Subsequent lines of therapy may explain the long survival achieved in our series. These results invite to design studies to elucidate the best therapeutic sequence in patients with SCCHN in the immunotherapy era. IMPLICATIONS FOR PRACTICE: Cetuximab-based salvage chemotherapy (SCAI) achieved high response rates in patients with recurrent/metastatic squamous cell cancer of the head and neck (SCCHN) after progression to PD-1/PD-L1 inhibitors. Objective response rate was higher than and progression-free survival was comparable to that of chemotherapy administered before immunotherapy (IO). In most patients, SCAI consisted of weekly, well-tolerated regimens. These observations have implications for current practice because of the limited evidence to date in SCCHN and the scant therapeutic options in this disease and invite to elucidate which may be the best treatment sequence for patients with head and neck cancer in the IO era.

Ber-EP4 staining in effusion cytology: A potential source of false positives.

The distinction between reactive mesothelium and carcinoma in serous effusions can be very difficult. Immunocytochemistry (ICC) is the most widely used tool to improve the diagnostic accuracy of body fluid cytology, with several ICC markers being proposed. Ber-EP4 antibody has shown high sensitivity and specificity rates for diagnosing metastatic carcinoma. In our department, we have detected Ber-EP4 positivity in mesothelium in some cytological specimens. We reviewed all articles on Ber-EP4 staining in effusion cytology, summarized current findings and analyzed the staining pattern of all cases expressing Ber-EP4. Some cases showing Ber-EP4 positivity in mesothelium have been reported, most of which showed only weak Ber-EP4 staining or staining of less than 50% of mesothelial cells. However, some cases may show strong positivity both in cytological and histological specimens. Clinicians and pathologists should be aware of this source of misdiagnosis, and ICC results in mesothelium should be always interpreted cautiously and correlated with clinical tests, other ICC markers and patient's previous history.

Major and durable response to second-line pembrolizumab-carboplatin-paclitaxel in an oral cavity cancer patient.

Many patients with recurrent/metastatic squamous cell cancer of the head and neck (SCCHN) are old or fragile and, despite deserving rapid and deep responses due to symptoms or a high tumor burden, they are not candidates for the current standard in the first-line setting of pembrolizumab plus platinum-5-FU. Other chemoimmunotherapy combinations substituting the 5-FU infusion by a taxane, may allow for less toxic effects without the need for a central venous catheter placement while maintaining efficacy. We present the case of an oral cavity cancer progressing with bulky disease to first-line cetuximab-paclitaxel in a frail and malnourished patient, where second-line treatment with pembrolizumab and reduced-dose 3-weekly carboplatin-paclitaxel achieved a deep and durable response. This is, to our knowledge, the first reported case of such combination being used in the R/M setting of SCCHN. Clinical trials should try to investigate the feasibility of this potentially less toxic and convenient combination in patients with SCCHN.

Not All Heart Uptakes on 99mTc-DPD Scintigraphy Are Amyloidosis: Chloroquine-Induced Cardiomyopathy.

ABSTRACT: This was the case of a 61-year-old woman with a medical history significant for hypertension and rheumatoid arthritis treated with chloroquine for the last 10 years. She was admitted to our hospital for heart failure symptoms. Echocardiography revealed severe concentric left ventricular hypertrophy. Serum and urine immunofixation electrophoresis and serum light chain assay were negative. No late gadolinium enhancement was observed on cardiovascular magnetic resonance. 99mTc-99mTc-DPD (3,3-diphosphono-1,2-propanodicarboxylic acid) scintigraphy showed myocardial uptake (Perugini score 2/3). Genetic testing excluded hereditary transthyretin cardiac amyloidosis. Endomyocardial biopsy analysis did not show findings suggestive of amyloidosis but consistent with chloroquine toxicity. Chloroquine-mediated cardiotoxicity is rare, and there are very few reports about bone scintigraphy imaging features.

Diagnosing Aortic Intramural Hematoma: Current Perspectives.

Aortic intramural hematoma (AIH) is an entity within the acute aortic syndrome. Combination of a priori probability, clinical history, laboratory blood test and imaging techniques are the basis for diagnosis of AIH. This review is focused on all aspects related to diagnosis of patients with AIH, from clinical to imaging and analytical.

IgG4-aortitis among thoracic aortic aneurysms.

OBJECTIVE: The incidence of aortitis in patients with thoracic aortic diseases is not well established. The aim of this study was to analyse the frequency and clinical course of patients with aortitis in a surgical series. METHODS: 320 consecutive patients with ascending aorta/aortic arch aneurysm or acute aortic syndrome who underwent surgery from 2012 to 2017 in a single tertiary referral hospital were retrospectively reviewed. Epidemiological data, clinical course and variables related to diagnosis, treatment and follow-up were collected from patients with histologically proven aortitis. RESULTS: From 320 examined aortic samples, 279 (87.2%) thoracic aneurysms and 41 acute aortic syndromes (12.8%), 9 (2.8%) were aortitis: 3 cases of Takayasu's arteritis, 3 of IgG4-related aortitis, 2 of giant cell, and 1 classified as idiopathic. Median age at surgery was 53.4 (51-69.2) years and six cases were female. Seven patients presented with non-specific symptoms and the diagnosis was made at pathology. Surgery was elective in eight patients and emergent in one case of IgG4-related aortitis. 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) was performed for disease extension study and as a monitoring technique during the follow-up of five patients, with just one case performed presurgically. All the patients with IgG4-related disease showed extrathoracic aortic involvement. There were no deaths, neither in-hospital nor during the 1.7 years of median follow-up. CONCLUSIONS: In surgically treated thoracic aorta pathology, the frequency of aortitis is low; IgG4-related disease is among the most common aetiologies with a frequency similar to other types of aortitis, such as Takayasu's and giant cell arteritis, and clinical manifestations are non-specific making presurgical diagnosis difficult. 18F-FDG PET/CT allows a better assessment of disease extension and therapeutic response. Surgery can be successfully performed and corticosteroid therapy ensures a good mid-term follow-up.

Durable intracranial and extracranial response to nivolumab with appearance of secondary resistance in a heavily pretreated patient with head and neck cancer.

BACKGROUND: Recently, nivolumab was approved in the second-line setting of squamous cell cancer of the head and neck (SCCHN). The benefits of PD-(L)1 inhibitors in PD-L1(-) tumors are unclear, and no reports exist on the activity of these agents in brain metastases from SCCHN. Little is known regarding the mechanisms underlying acquired resistance to PD-(L)1 inhibition. METHODS: A patient with PD-L1(-) metastatic SCCHN progressing to cetuximab-based chemotherapy received third-line nivolumab. T cell infiltration and mRNA expression of immune-related genes were compared in prenivolumab and postnivolumab biopsies from a progressing tumor lesion. RESULTS: An exceptional local and systemic response was achieved, including complete devitalization of brain metastases that lasted for more than a year. Increased T cell infiltration and upregulation of genes related to T cell exhaustion and resistance to PD-1 inhibition were found. CONCLUSION: Durable responses to PD-(L)1 inhibitors may be observed in biomarker-negative SCCHN. Mechanisms of resistance should be studied.