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1.
Clin Lung Cancer ; 23(8): 686-693, 2022 12.
Article in English | MEDLINE | ID: mdl-36050243

ABSTRACT

BACKGROUND: Despite their anti-tumor efficacy, immune checkpoint inhibitors (ICIs) are associated with a variety of immune-related adverse events (irAEs). Grade ≥ 2 irAEs require ICI discontinuation. The decision to resume ICI treatment often remains challenging. METHODS: We retrospectively studied 1051 adult patients with stage IV non-small cell lung cancer (NSCLC) treated with ICIs at a single institution between January 2015 and December 2020, and identified 99 (9.4%) patients with grade≥2 irAEs necessitating treatment interruption. Forty patients underwent retreatment (rechallenged group), while 59 discontinued the treatment (discontinued group). RESULTS: Baseline characteristics of patients in the 2 groups were similar. Initial irAEs were less severe in the rechallenged group. After rechallenging, 24 of 40 (60%) patients had recurrence of the same or de-novo irAEs. Twenty (50%) developed second grade≥ 2 irAEs. No grade 4 irAE or irAE-related death occurred after rechallenging. Using multivariate analysis, no statistically significant differences in overall survival (OS) (HR: 1.10, 95% CI: 0.57-2.15, P = .77) or progression-free survival (PFS) (HR: 0.87, 95% CI: 0.45-1.71, P = .69) were noted between the 2 groups, while the best objective response prior to the initial irAEs was the only variable affecting OS and PFS. CONCLUSIONS: Rechallenge was associated with a relative high risk of second grade≥ 2 irAEs. The risk was less if the initial irAEs were resolved. No differences were seen in survival outcomes of patients who had ICI rechallenge and those who did not. Permanent ICI discontinuation is an appropriate strategy after grade≥ 2 irAEs, especially severe irAEs.


Subject(s)
Antineoplastic Agents, Immunological , Carcinoma, Non-Small-Cell Lung , Drug-Related Side Effects and Adverse Reactions , Lung Neoplasms , Adult , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Immune Checkpoint Inhibitors/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Lung Neoplasms/pathology , Retrospective Studies , Drug-Related Side Effects and Adverse Reactions/etiology
2.
J Natl Compr Canc Netw ; 17(4): 302-310, 2019 04 01.
Article in English | MEDLINE | ID: mdl-30959462

ABSTRACT

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans
3.
J Natl Compr Canc Netw ; 15(5): 563-573, 2017 05.
Article in English | MEDLINE | ID: mdl-28476736

ABSTRACT

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Humans , United States
4.
J Clin Oncol ; 35(2): 157-165, 2017 Jan 10.
Article in English | MEDLINE | ID: mdl-27870574

ABSTRACT

Purpose This two-part, first-in-human study was initiated in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors (FGFRs) to determine the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor. Patients and Methods Adult patients were treated with escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily continuously in 28-day cycles. During expansion at the MTD, patients with FGFR1-amplified squamous cell non-small-cell lung cancer (sqNSCLC; arm 1) or other solid tumors with FGFR genetic alterations (mutations/amplifications/fusions) received BGJ398 daily on a continuous schedule (arm 2), or on a 3-weeks-on/1-week-off schedule (arm 3). Results Data in 132 patients from the escalation and expansion arms are reported (May 15, 2015, cutoff). The MTD, 125 mg daily, was determined on the basis of dose-limiting toxicities in four patients (100 mg, grade 3 aminotransferase elevations [n = 1]; 125 mg, hyperphosphatemia [n = 1]; 150 mg, grade 1 corneal toxicity [n = 1] and grade 3 aminotransferase elevations [n = 1]). Common adverse events in patients treated at the MTD (n = 57) included hyperphosphatemia (82.5%), constipation (50.9%), decreased appetite (45.6%), and stomatitis (45.6%). A similar safety profile was observed using the 3-weeks-on/1-week-off schedule (RP2D). However, adverse event-related dose adjustments/interruptions were less frequent with the 3-weeks-on/1-week-off (50.0%) versus the continuous (73.7%) schedule. Antitumor activity (seven partial responses [six confirmed]) was demonstrated with BGJ398 doses ≥ 100 mg in patients with FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancer. Conclusion BGJ398 at the MTD/RP2D had a tolerable and manageable safety profile and showed antitumor activity in several tumor types, including FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancers.


Subject(s)
Antineoplastic Agents/administration & dosage , Phenylurea Compounds/administration & dosage , Pyrimidines/administration & dosage , Receptors, Fibroblast Growth Factor/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Agents/blood , Antineoplastic Agents/pharmacokinetics , Female , Humans , Hyperphosphatemia/chemically induced , Male , Maximum Tolerated Dose , Middle Aged , Phenylurea Compounds/adverse effects , Phenylurea Compounds/blood , Phenylurea Compounds/pharmacokinetics , Pyrimidines/adverse effects , Pyrimidines/blood , Pyrimidines/pharmacokinetics
5.
J Natl Compr Canc Netw ; 12(8): 1152-82, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25099447

ABSTRACT

Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma), gall bladder, and bile ducts (cholangiocarcinomas). Gallbladder cancer and cholangiocarcinomas are collectively known as biliary tract cancers. Gallbladder cancer is the most common and aggressive type of all the biliary tract cancers. Cholangiocarcinomas are diagnosed throughout the biliary tree and are typically classified as either intrahepatic or extrahepatic cholangiocarcinoma. Extrahepatic cholangiocarcinomas are more common than intrahepatic cholangiocarcinomas. This manuscript focuses on the clinical management of patients with gallbladder cancer and cholangiocarcinomas (intrahepatic and extrahepatic).


Subject(s)
Bile Duct Neoplasms/therapy , Carcinoma, Hepatocellular/therapy , Cholangiocarcinoma/therapy , Gallbladder Neoplasms/therapy , Bile Duct Neoplasms/epidemiology , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Carcinoma, Hepatocellular/pathology , Cholangiocarcinoma/epidemiology , Cholangiocarcinoma/pathology , Gallbladder Neoplasms/epidemiology , Gallbladder Neoplasms/pathology , Guidelines as Topic , Humans , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Randomized Controlled Trials as Topic
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