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Video to go with: Prolonging the life of people with metastatic breast cancer in routine clinical practice by adding palbociclib to an aromatase inhibitor from a real-world database analysis: a plain language summary

Additional file 1.

Additional file 2.

Supplemental material, sj-docx-1-tam-10.1177_17588359211039928 for ALBI score and outcomes in patients with hepatocellular carcinoma: post hoc analysis of the randomized controlled trial KEYNOTE-240 by Arndt Vogel, Philippe Merle, Chris Verslype, Richard S. Finn, Andrew X. Zhu, Ann-Lii Cheng, Stephen Lam Chan, Thomas Yau, Baek-Yeol Ryoo, Jennifer Knox, Bruno Daniele, Shukui Qin, Ziwen Wei, Yanna Miteva, Usha Malhotra, Abby B. Siegel and Masatoshi Kudo in Therapeutic Advances in Medical Oncology

Additional file 2. Patient Characteristics After PSM.

Additional file 3. Forest Plot of Real-World Progression-Free Survival by Subgroup After PSM*.

Additional file 4. Forest Plot of Overall Survival by Subgroup* After PSM.

Supplemental material, sj-docx-1-tam-10.1177_17588359211039928 for ALBI score and outcomes in patients with hepatocellular carcinoma: post hoc analysis of the randomized controlled trial KEYNOTE-240 by Arndt Vogel, Philippe Merle, Chris Verslype, Richard S. Finn, Andrew X. Zhu, Ann-Lii Cheng, Stephen Lam Chan, Thomas Yau, Baek-Yeol Ryoo, Jennifer Knox, Bruno Daniele, Shukui Qin, Ziwen Wei, Yanna Miteva, Usha Malhotra, Abby B. Siegel and Masatoshi Kudo in Therapeutic Advances in Medical Oncology

Additional file 3. Forest Plot of Real-World Progression-Free Survival by Subgroup After PSM*.

Additional file 1. Patient Attrition Diagram.

Hepatocellular carcinoma (HCC) is a leading cause of mortality. Checkpoint inhibitors of programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown great efficacy, but lack biomarkers that predict response. Circulating tumor cells (CTCs) have promise as a liquid-biopsy biomarker; however, data on HCC CTCs expressing PD-L1 have not been reported. We sought to detect PD-L1-expressing HCC-CTCs and investigated their role as a prognostic and predictive biomarker. Using an antibody-based platform, CTCs were enumerated/phenotyped from a prospective cohort of 87 patients with HCC (49 early-stage, 22 locally advanced, and 16 metastatic), 7 patients with cirrhosis, and 8 healthy controls. Immunocytochemistry identified total HCC CTCs (4',6-diamidino-2-phenylindole-positive [DAPI+]/cytokeratin-positive [CK+]/clusters of differentiation 45-negative [CD45-]) and a subpopulation expressing PD-L1 (DAPI+/CK+/PD-L1+/CD45-). PD-L1+ CTCs were identified in 4 of 49 (8.2%) early-stage patients, but 12 of 22 (54.5%) locally advanced and 15 of 16 (93.8%) metastatic patients, accurately discriminating early from locally advanced/metastatic HCC (sensitivity=71.1%, specificity=91.8%, area under the receiver operating characteristic curve=0.807; P&nbsp

Additional file 1 : Table S1. Summary of the PALOMA Clinical Trial Data. Table S2. Schedule of Per Protocol Palbociclib Dose Reductions and Modifications. Table S3. Time Points for Assessing Frequency of AEs Both Before and After Palbociclib Dose Reductions. Table S4. Incidence of Hematologic Adverse Events Before/After Palbociclib Dose Reduction From 125 to 100 mg: Asian/non-Asian. Table S5. Incidence of Hematologic Adverse Events Before/After Palbociclib Dose Reduction From 125 to 100 mg: BMI. Table S6. Incidence of Hematologic Adverse Events Before/After Palbociclib Dose Reduction From 125 to 100 mg: Age. Figure S1. Study Design of PALOMA-1, PALOMA-2, and PALOMA-3.

BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease with diverse underlying aetiologies. REACH/REACH-2 were global phase III studies investigating ramucirumab in advanced HCC (aHCC) following sorafenib treatment. We performed an exploratory analysis of outcomes by liver disease aetiology and baseline serum viral load. METHODS Meta-analysis was conducted in patients with aHCC and alpha-fetoprotein (AFP) ≥400 ng/mL (N = 542) from REACH/REACH-2 trials. Individual patient-level data were pooled with results reported by aetiology subgroup (hepatitis B [HBV] or C [HCV] and Other). Pre-treatment serum HBV DNA and HCV RNA were quantified using Roche COBAS AmpliPrep/COBAS TaqMan. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox proportional hazard model (stratified by study). RESULTS Baseline characteristics were generally balanced between arms in each subgroup (HBV: N = 225, HCV: N = 127, Other: N = 190). No significant difference in treatment effect by aetiology subgroup was detected (OS interaction P-value = .23). Median OS (ramucirumab vs placebo) in months was 7.7 versus 4.5 (HR 0.74, 95% CI 0.55-0.99) for HBV, 8.2 versus 5.5 (HR 0.82, 95% CI 0.55-1.23) for HCV and 8.5 versus 5.4 (HR 0.56, 95% CI 0.40-0.79) for Other. Ramucirumab showed similar overall safety profiles across subgroups. Worst outcomes were noted in patients with a detectable HBV load. Use of HBV antiviral therapy, irrespective of viral load, was beneficial for survival, liver function and liver-specific adverse events. CONCLUSIONS Ramucirumab improved survival across aetiology subgroups with a tolerable safety profile, supporting its use in patients with aHCC and elevated AFP.