Current Systemic Treatment Options for Metastatic and Unresectable Pancreatic Cancer

Metastatic and local advanced unresectable pancreatic cancers are lethal conditions that always carry a poor prognosis with rare exceptions. Currently, the mainstay of therapy is cytotoxic chemotherapy plus best supportive care. First-line therapy for patients with a good performance status includes FOLFIRINOX or gemcitabine plus nab-paclitaxel regimens. Patients carrying a deleterious germline BRCA mutation can be treated with maintenance olaparib after FOLFIRINOX. Patients with a poor performance status, but still fit enough for chemotherapy, may be treated with single agent gemcitabine. Second-line therapy will depend on previous therapy and current performance status. Options for patients treated with gemcitabine-based regimens are 5-fluorouracil plus leucovorin plus either nanoliposomal irinotecan, irinotecan or oxaliplatin. Patients that were treated with first line FOLFIRINOX may benefit from a gemcitabine-based chemotherapy, but evidence from randomized trials is lacking. Other options like immunotherapy and targeted therapies yield benefit only in very selected cases, and it is still an area of research

Neoadjuvant Treatment for Nonmetastatic Pancreatic Cancer

Pancreatic adenocarcinoma is one of the most lethal malignancies among solid tumors. Unfortunately, several patients are diagnosed at metastatic stage or with unresectable disease due to vascular compromise involving the pancreas without any chance of curative treatment. There are also two other groups of patients: resectable patients at upfront diagnosis and “borderline resectable” pancreatic cancer patients. This last group represents those patients where surgery is not always possible without a preoperative treatment allowing surgeons to perform an R0 resection. Achieving an R0 resection is the only curative option for pancreatic cancer patients; nevertheless, many R0-resected patients will relapse within 2 years from surgery. Despite adjuvant treatment, reported median overall survival is only 28 months for patients with resectable pancreatic adenocarcinoma; thus, neoadjuvant treatment has been explored in order to improve survival. We aim to describe the controversial reported data and to show the recommendations that are suggested for these patients; however, we need to remark that there is no strong data that support neoadjuvant treatment. Currently, clinical trials are ongoing, and probably soon this approach will become a standard of care among borderline resectable patients and probably in selected resectable patients too

Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma

BackgroundAdjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.MethodsIn this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent. A significant improvement in disease-free survival according to investigator assessment (the primary end point) was shown previously. Overall survival was the key secondary end point. Safety was a secondary end point.Download a PDF of the Research Summary.ResultsA total of 496 participants were assigned to receive pembrolizumab and 498 to receive placebo. As of September 15, 2023, the median follow-up was 57.2 months. The disease-free survival benefit was consistent with that in previous analyses (hazard ratio for recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87). A significant improvement in overall survival was observed with pembrolizumab as compared with placebo (hazard ratio for death, 0.62; 95% CI, 0.44 to 0.87; P=0.005). The estimated overall survival at 48 months was 91.2% in the pembrolizumab group, as compared with 86.0% in the placebo group; the benefit was consistent across key subgroups. Pembrolizumab was associated with a higher incidence of serious adverse events of any cause (20.7%, vs. 11.5% with placebo) and of grade 3 or 4 adverse events related to pembrolizumab or placebo (18.6% vs. 1.2%). No deaths were attributed to pembrolizumab therapy.ConclusionsAdjuvant pembrolizumab was associated with a significant and clinically meaningful improvement in overall survival, as compared with placebo, among participants with clear-cell renal-cell carcinoma at increased risk for recurrence after surgery. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.

Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma

BACKGROUND: Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. METHODS: In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point. RESULTS: A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred. CONCLUSIONS: Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.)

Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

BACKGROUND: The first interim analysis of the KEYNOTE-564 study showed improved disease-free survival with adjuvant pembrolizumab compared with placebo after surgery in patients with clear cell renal cell carcinoma at an increased risk of recurrence. The analysis reported here, with an additional 6 months of follow-up, was designed to assess longer-term efficacy and safety of pembrolizumab versus placebo, as well as additional secondary and exploratory endpoints. METHODS: In the multicentre, randomised, double-blind, placebo-controlled, phase 3 KEYNOTE-564 trial, adults aged 18 years or older with clear cell renal cell carcinoma with an increased risk of recurrence were enrolled at 213 hospitals and cancer centres in North America, South America, Europe, Asia, and Australia. Eligible participants had an Eastern Cooperative Oncology Group performance status of 0 or 1, had undergone nephrectomy 12 weeks or less before randomisation, and had not received previous systemic therapy for advanced renal cell carcinoma. Participants were randomly assigned (1:1) via central permuted block randomisation (block size of four) to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for up to 17 cycles. Randomisation was stratified by metastatic disease status (M0 vs M1), and the M0 group was further stratified by ECOG performance status and geographical region. All participants and investigators involved in study treatment administration were masked to the treatment group assignment. The primary endpoint was disease-free survival by investigator assessment in the intention-to-treat population (all participants randomly assigned to a treatment). Safety was assessed in the safety population, comprising all participants who received at least one dose of pembrolizumab or placebo. As the primary endpoint was met at the first interim analysis, updated data are reported without p values. This study is ongoing, but no longer recruiting, and is registered with ClinicalTrials.gov, NCT03142334. FINDINGS: Between June 30, 2017, and Sept 20, 2019, 994 participants were assigned to receive pembrolizumab (n=496) or placebo (n=498). Median follow-up, defined as the time from randomisation to data cutoff (June 14, 2021), was 30·1 months (IQR 25·7-36·7). Disease-free survival was better with pembrolizumab compared with placebo (HR 0·63 [95% CI 0·50-0·80]). Median disease-free survival was not reached in either group. The most common all-cause grade 3-4 adverse events were hypertension (in 14 [3%] of 496 participants) and increased alanine aminotransferase (in 11 [2%]) in the pembrolizumab group, and hypertension (in 13 [3%] of 498 participants) in the placebo group. Serious adverse events attributed to study treatment occurred in 59 (12%) participants in the pembrolizumab group and one (<1%) participant in the placebo group. No deaths were attributed to pembrolizumab. INTERPRETATION: Updated results from KEYNOTE-564 support the use of adjuvant pembrolizumab monotherapy as a standard of care for participants with renal cell carcinoma with an increased risk of recurrence after nephrectomy. FUNDING: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA

Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227

[Purpose] We present 5-year results from CheckMate 227 Part 1, in which nivolumab plus ipilimumab improved overall survival (OS) versus chemotherapy in patients with metastatic non–small-cell lung cancer, regardless of tumor programmed death ligand 1 (PD-L1) status.[Methods] Adults with stage IV/recurrent non–small-cell lung cancer without EGFR mutations or ALK alterations and with tumor PD-L1 ≥ 1% or < 1% (n = 1739) were randomly assigned. Patients with tumor PD-L1 ≥ 1% were randomly assigned to first-line nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. Patients with tumor PD-L1 < 1% were randomly assigned to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. End points included exploratory 5-year results for efficacy, safety, and quality of life.[Results] At a minimum follow-up of 61.3 months, 5-year OS rates were 24% versus 14% for nivolumab plus ipilimumab versus chemotherapy (PD-L1 ≥ 1%) and 19% versus 7% (PD-L1 < 1%). The median duration of response was 24.5 versus 6.7 months (PD-L1 ≥ 1%) and 19.4 versus 4.8 months (PD-L1 < 1%). Among patients surviving 5 years, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) were off nivolumab plus ipilimumab without initiating subsequent systemic anticancer treatment by the 5-year time point. Survival benefit continued after nivolumab plus ipilimumab discontinuation because of treatment-related adverse events, with a 5-year OS rate of 39% (combined PD-L1 ≥ 1% and < 1% populations). Quality of life in 5-year survivors treated with nivolumab plus ipilimumab was similar to that in the general US population through the 5-year follow-up. No new safety signals were observed.[Conclusion] With all patients off immunotherapy treatment for ≥ 3 years, nivolumab plus ipilimumab increased 5-year survivorship versus chemotherapy, including long-term, durable clinical benefit regardless of tumor PD-L1 expression. These data support nivolumab plus ipilimumab as an effective first-line treatment for patients with metastatic non–small-cell lung cancer.Peer reviewe

The current situation for gastric cancer in Chile

Gastric cancer is a neoplasm with a high incidence and mortality rate in Chile where more than 3000 people die every year from this type of cancer. This study shows the clinical and epidemiological considerations of this disease, information about translational research on this pathology in Chile, the contribution of Chilean doctors to the development of gastric cancer management awareness and the general situation of gastric cancer in Chile

Hepatocellular carcinoma in identical twins in Chile: case report

Liver cancer is the second leading cause of cancer death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary malignant liver tumour, with a typically poor prognosis, growing incidence and a well-documented relationship with chronic inflammation factors of the liver tissue. Despite the fact that family medical history has been identified as a risk factor for the development of HCC, its significance in terms of etiopathogenesis and prognosis is not well documented. With a view to contributing to this discussion, we will report the clinical case of two identical twins with HCC, both diagnosed within a short period of time, by providing relevant clinical data, and relating this to other medical literature reports that could contribute to a deeper understanding of this illness