Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: updated results of the phase III KEYNOTE-048 study

Purpose: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented. Methods: Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Efficacy was evaluated in programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, CPS ≥ 1, and total populations, with no multiplicity or alpha adjustment. Results: The median study follow-up was 45.0 months (interquartile range, 41.0-49.2; n = 882). At data cutoff (February 18, 2020), overall survival improved with pembrolizumab in the PD-L1 CPS ≥ 20 (hazard ratio [HR], 0.61; 95% CI, 0.46 to 0.81) and CPS ≥ 1 populations (HR, 0.74; 95% CI, 0.61 to 0.89) and was noninferior in the total population (HR, 0.81; 95% CI, 0.68 to 0.97). Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS ≥ 1 (HR, 0.64; 95% CI, 0.53 to 0.78), and total (HR, 0.71; 95% CI, 0.59 to 0.85) populations. The objective response rate on second-course pembrolizumab was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.84) and CPS ≥ 1 (HR, 0.79; 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.86), CPS ≥ 1 (HR, 0.66; 95% CI, 0.55 to 0.81), and total (HR, 0.73; 95% CI, 0.61 to 0.88) populations. PFS2 was similar after pembrolizumab and longer after pembrolizumab-chemotherapy on next-line taxanes and shorter after pembrolizumab and similar after pembrolizumab-chemotherapy on next-line nontaxanes. Conclusion: With a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy continued to demonstrate survival benefit versus cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Patients responded well to subsequent treatment after pembrolizumab-based therapy

SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial.

BACKGROUND: Adding bevacizumab to chemotherapy improves response rates and progression-free survival (PFS) in metastatic breast cancer (mBC). We aimed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab. METHODS: This multicenter, randomized phase III trial compared bevacizumab with either paclitaxel (arm A) or daily oral capecitabine-cyclophosphamide (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. The primary endpoint was the incidence of selected grade 3-5 adverse events (AE) including: febrile neutropenia, infection, sensory/motor neuropathy, and mucositis. Secondary endpoints included objective response rate, disease control rate, PFS, overall survival (OS), quality of life (QoL), and pharmacoeconomics. The study was registered prospectively with ClinicalTrials.gov, number NCT01131195 on May 25, 2010. RESULTS: Between September 2010 and December 2012, 147 patients were included at 22 centers. The incidence of primary endpoint-defining AEs was similar in arm A (25 % [18/71]; 95 % CI 15-35 %) and arm B (24 % [16/68]; 95 % CI 13-34 %; P = 0.96). Objective response rates were 58 % (42/73; 95 % CI 0.46-0.69) and 50 % (37/74; 95 % CI 0.39-0.61) in arms A and B, respectively (P = 0.45). Median PFS was 10.3 months (95 % CI 8.7-11.3) in arm A and 8.5 months (95 % CI 6.5-11.9) in arm B (P = 0.90). Other secondary efficacy endpoints were not significantly different between study arms. The only statistically significant differences in QoL were less hair loss and less numbness in arm B. Treatment costs between the two arms were equivalent. CONCLUSION: This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3-5 AEs with metronomic bevacizumab, cyclophosphamide and capecitabine

Standards und häufige Fragen: Tumoren des Kopf-Hals-Bereichs

Bei Tumoren des Kopf-Hals-Bereichs stellen Plattenepithelkarzinome (Head & Neck Squamous Cell Carcinoma, HNSCC) die häufigste Histologie dar und machen mehr als 90% aller malignen Erkrankungen dieser Region aus. Die durch die «klassischen» Risikofaktoren, Nikotin- und Alkoholkonsum, verursachten HNSCC treten im ganzen oberen Aerodigestivtrakt auf

18FDG-PET-CT identifies histopathological non-responders after neoadjuvant chemotherapy in locally advanced gastric and cardia cancer: cohort study

BACKGROUND Pathologic response to neoadjuvant chemotherapy (neoCTX) is a prognostic factor in many cancer types, and early prediction would help to modify treatment. In patients with gastric and esophagogastric junction (AEG) cancer, the accuracy of FDG PET-CT to predict early pathologic response after neoadjuvant chemotherapy (neoCTX) is currently not known. METHODS From a consecutive cohort of 72 patients, 44 patients with resectable, locally-advanced gastric cancer or AEG Siewert type II and III received neoCTX after primary staging with endoscopic ultrasound, PET-CT and laparoscopy. Overall, 14 patients did not show FDG uptake, and the remaining 30 were restaged by PET-CT 14 days after the first cycle of neoCTX. Metabolic response was defined as decrease of tumor standardized uptake value (SUV) by ≥35%. Major pathologic regression was defined as less than 10% residual tumor cells. RESULTS Metabolic response after neoCTX was detected in 20/30 (66.7%), and non-response in 10/30 (33.3%) patients. Among metabolic responders, n = 10 (50%) showed major and n = 10 (50%) minor pathologic regression. In non-responders, n = 9 (90%) had minor and 1 (10%) a major pathologic regression. This resulted in a sensitivity of 90.9%, specificity 47.3%, positive predictive value 50%, negative predictive value 90% and accuracy of 63.3%. CONCLUSION Response PET-CT after the first cycle of neoCTX does not accurately predict overall pathologic response. However, PET-CT reliably detects non-responders, and identifies patients who should either immediately proceed to resection or receive a modified multimodality therapy. TRIAL REGISTRATION The trial was registered and approved by local ethics committee PB_2016-00769

IMRT/VMAT for malignancies in the head-and-neck region : Outcome in patients aged 80

OBJECTIVE Elderly patients with malignant head-and-neck tumors (HNT) often pose a therapeutic challenge. They frequently have significant comorbidities which may influence their ability to tolerate tumor-specific therapies. Our aim was to investigate the outcome of patients aged 80+ years undergoing curative intent intensity- or volume-modulated radiation therapy (IMRT/VMAT). METHODS We retrospectively reviewed our HNT patients aged 80+ treated with curative IMRT/VMAT from December 2003 to November 2015. Overall survival (OS), disease-free survival (DFS), local control (LC), and treatment tolerance were assessed. Outcome results were compared with that of a younger HNT patient cohort from our hospital. RESULTS A total of 140 consecutive patients were included (65 postoperative, 75 definitive). Mean/median age at treatment start was 84.8/84.1 years (range 80-96 years). Mean/median follow-up time was 25/16 months (range 2-92 months). Of the 140 patients, 80 were alive with no evidence of disease when last seen, 28 had died due to the cancer, 12 remained alive with disease, the remaining 20 died intercurrently. Systemic concomitant therapy was administered in 7 %. Late grade 3-4 toxicity was observed in 2 %. All patients completed treatment. Hospitalization and feeding tube rates were 26 % and 11 %, respectively. The 2‑/3-year LC, DFS, and OS rates for the entire cohort were 81/80 %, 69/63 %, and 68/66 %, respectively. Squamous cell carcinoma (SCC) patients showed an inferior 3-year OS rate as compared to non-SCC patients (62 % vs 77 %, p = 0.0002), while LC and DFS did not differ. Patients undergoing postoperative radiation attained a higher OS compared to the definitively irradiated subgroup with 74 vs. 60 % at 3 years (p = 0.01); however, DFS rates were similar for both groups (68 vs. 61 %, p = 0.15). Corresponding rates for >1400 HNT patients <80 years treated during the same time interval were 81/80 %, 69/67 %, and 77/72 %, respectively. CONCLUSIONS Treatment tolerance in our patients aged 80+ was high. These results suggest that elderly HNT patients should not be denied potentially curative treatment strategies

Impact of tumor volume and systemic therapy on outcome in patients undergoing IMRT for large volume head neck cancer

BACKGROUND: Former prospective analyses revealed gross tumor volume (GTV) as the most reliable parameter to statistically significantly predict disease control in head neck cancer (HNC) patients treated with definitive intensity modulated radiation therapy (IMRT) +/-concomitant systemic therapy. The most 'unfavourable' subgroup was characterized by total GTV (tGTV) of > 70 cc, translating in ~50 and 65% 3-year disease free (DFS) and overall survival (OAS, vs 68% and 88% in tGTV 70 cc, which only marginally benefits from intensive curative treatment. RESULTS: Between 03/2002-03/2011, 112 HNC patients with tGTV > 70 cc were definitively irradiated with curative intention. Mean tGTV was 104 cc (71-251). 98/112 (88%) patients underwent systemic therapy. Parameters with potential impact on disease outcome were retrospectively tested. The 3-year local-regional control (LRC), DFS and OAS rates were 61%, 50%, and 58%. The used cut-off value of 130 cc revealed an inverse association between tGTV and outcome. Patients able to undergo any systemic therapy (n = 98, mean tGTV0 103 cc, mean age 60 years) showed a satisfying and significantly superior outcome compared to the subgroup with radiation alone (n = 14, mean tGTV 99 cc, mean age 73 years), with 53% vs 17% 3-year DFS (p = 0.01). Radiation alone for tGTV > 130 cc failed to aim its curative goal in 3/3 patients. CONCLUSION: Patients with tGTV > 70 cc unable to undergo any systemic therapy represented a subgroup in which disease control was achievable in ~130 cc fails to meet its curative aim

Neuer Therapieansatz mit Denosumab bei Riesenzellgranulomen. Ein Fallbeispiel

Riesenzellgranulome stellen die Patienten und den Behandler vor eine grosse Herausforderung. Die frühzeitige Diagnose durch den Zahnarzt und die zeitnahe Therapie sind essentiell