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The article presents abstracts on medical topics which include acute chemotherapy-related toxicity in BRCA1 and BRCA2 mutation carriers treated for breast cancer in Great Britain, neoadjuvant endocrine therapy for locally advanced breast cancer, and human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer.

Background: In the phase 3 KEYNOTE-040 study, pembrolizumab prolonged OS versus chemotherapy in previously treated recurrent or metastatic (R/M) HNSCC. We present a post hoc subgroup analysis by disease recurrence pattern: recurrent-only, recurrent and metastatic (recurrent-metastatic), and metastatic-only HNSCC., Materials and Methods: Patients had HNSCC that progressed during or after platinum-containing treatment for R/M disease or had recurrence or progression within 3-6 months of previous platinum-containing definitive therapy for locally advanced disease. Patients were randomly assigned (1:1) to pembrolizumab 200 mg Q3W or investigator's choice of standards of care (SOC): methotrexate, docetaxel, or cetuximab. Outcomes included OS, PFS, ORR, and DOR. The data cutoff was May 15, 2017., Results: There were 125 patients (pembrolizumab, 53; SOC, 72) in the recurrent-only subgroup, 204 in the recurrent-metastatic subgroup (pembrolizumab, 108; SOC, 96), and 166 in the metastatic-only subgroup (pembrolizumab, 86; SOC, 80). The hazard ratio (95% CI) for death for pembrolizumab versus SOC was 0.83 (0.55-1.25) in the recurrent-only, 0.78 (0.58-1.06) in the recurrent-metastatic, and 0.74 (0.52-1.05) in the metastatic-only subgroups. PFS was similar between treatment arms in all subgroups. ORR was 22.6% for pembrolizumab versus 16.7% for SOC in the recurrent-only, 10.2% versus 6.3% in the recurrent-metastatic, and 15.1% versus 8.8% in the metastatic-only subgroups. DOR was numerically longer with pembrolizumab in all subgroups., Conclusion: Pembrolizumab provided numerically longer OS and durable responses in all subgroups compared with SOC, suggesting that patients with previously treated R/M HNSCC benefit from pembrolizumab regardless of recurrence pattern., Competing Interests: Declaration of Competing Interest KJH reports honoraria from BMS, Merck-Serono, MSD, and Replimune; advisory/consultancy roles with Arch Oncology, AstraZeneca, BMS, Boehringer-Ingelheim, Codiak, Eisai, Inzen, Merck-Serono, MSD, Oncolys, Pfizer, and Replimune; speaker bureau for BMS, Merck-Serono, MSD, and Replimune; and research grant/funding from AstraZeneca, Boehringer-Ingelheim, and Replimune. EEWC reports advisory/consultancy roles with Axelia, Cel Sci, Eisai, Hoopika, ImmunoSensor, Istari, Janssen, Kahr Medical, Mana Therapeutics, Merck, Mirati, MSD, Nectin Tx, Pangea Therapeutics, and Roche; is a member of the board of directors for Psiouxus Therapeutics, and NCCN; has stock/shares with Kinnate Biopharma and Primmune Therapeutics; and has a leadership role with Ayala, Kura, and Kinnate Biopharma DS reports advisory/consultancy roles with Merck and Adlai-Nortye and research grant/funding from Merck, GSK, Adlai-Nortye, and BMS. JD reports advisory/consultancy role with Roche, PharmaMar, BMS, Merck Serono, and MSD; is a principal investigator for studies from Roche, BI, and MSD; and travel expenses from PharmaMar. LL reports research funding from Astrazeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Merck-Serono, MSD, Novartis, Pfizer, Roche, and Buran; and occasional fees for participation as a speaker at conferences/congresses or as a scientific consultant for advisory boards from Astrazeneca, Bayer, MSD, Merck-Serono, AccMed, and Neutron Therapeutics, Inc. MJA reports honoraria from AstraZeneca, Lilly, MSD, Merck, TAKEDA, ONO, Amgen, YUHAN, and Roche; advisory/consultancy roles with AstraZeneca, Lilly, MSD, Merck, TAKEDA, ONO, Amgen, YUHAN, Roche, and Alpha Pharmaceuticals; and research grant/funding from YUHAN. AS reports honoraria from MSD, Merck Serono, Novartis Pharma, Bristol Myers Squibb, Pierre Fabre, and Sanofi; and advisory/consultancy roles with MSD, Merck Serono, Novartis Pharma, Bristol Myers Squibb, Pierre Fabre, and Sanofi. JPM reports advisory/consultancy roles with Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Boerhinger, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, NEKTAR, F-Star, Seagen, Genmab, Astellas, and Psioxius; leadership roles with the EORTC head and neck group (Chair); travel/accommodation/expenses from Amgen, BMS, Pfizer, MSD, and Gilead; and non-remunerated activities with MSD (Advisory board). NM reports being a co-founder and shareholder MaxiVAX, a personalized cancer immunotherapy biotech, with ongoing Phase IIa in patients with advanced Head & Neck cancer; and being the Chief Medical Officer at MaxiVAX. RM reports advisor/consultancy role for Janssen, AstraZeneca (uncompensated), Coherus and Rakuten Medical; and research funding from Merck. BB reports advisory/consultancy roles with Genentech, Glaxo Smith Kline, Nektar, Debio, Merck KgA, Astra Zeneca,Vaccinex, Exelexis, Cue BioPharma, Fusion, Arvinas, Coherus, ALX Oncology, Hookipa Kura, Astra Zeneca/Medimmune, Nektar, and Roche; and research grant/funding from Cue Biopharma, Merck, Gilead, Exelexis, and Vaccinex. RFS reports employment at the time of the study at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; current employment at Carisma Therapeutics. JL reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and stock ownership in Merck & Co., Inc., Rahway, NJ, USA. JG reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and stock ownership in Merck & Co., Inc., Rahway, NJ, USA. NL reports employment at Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and stock ownership in Merck & Co., Inc., Rahway, NJ, USA. CLT reports honoraria from MSD, BMS, Merck Serono, Celgene, Astra Zeneca, Seattle Genetics, Maxivax, Seagen, and Roche; research grant/funding from MSD; and travel/accommodation/expenses from MSD, Merck Serono, Astra Zeneca, and BMS., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, PD-L1-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented., Patients and Methods: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1:1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary end point was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population., Results: Between May 5, 2016, and May 28, 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cutoff (November 30, 2020) was 45.1 months (interquartile range, 39.0-48.8). Median OS was 17.2 months (95% confidence interval [CI], 11.7-22.9) with pembrolizumab and 15.3 months (95% CI, 10.9-18.1) with chemotherapy (hazard ratio, 0.90 [95% CI, 0.67-1.19; P = 0.2262]). Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage)., Conclusion: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events., Clinical Trial Registry: ClinicalTrials.gov, NCT02611960., (Copyright © 2022. Published by Elsevier Ltd.)

Malignant lymphomas of the diffuse mixed or diffuse large cell subtype are immunologically heterogeneous and morphologic features do not allow prediction of lineage. Applications of immunophenotypic and gene rearrangement techniques has greatly improved our ability to determine clonality and lineage. Nevertheless, some diffuse lymphomas are composed of numerous reactive cells accompanying a small clonal population, thereby making determination of clonality difficult, even with gene rearrangement techniques. In this study, we report two malignant lymphomas in which immunophenotypic and genotypic studies failed to elucidate evidence of clonality. In both cases, the polymerase chain reaction amplified segments of DNA containing the bcl-2/JH sequence, providing evidence of clonality and suggesting B-cell lineage. We conclude that the polymerase chain reaction technique may be useful in the diagnosis of some diffuse mixed and large cell lymphomas.