Four-year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma.

BACKGROUND: In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA. PATIENTS AND METHODS: Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization). RESULTS: For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified. CONCLUSIONS: These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.

Behavioural insights and attitudes on community masking during the initial spread of COVID-19 in Hong Kong.

INTRODUCTION: Community face mask use during the coronavirus disease 2019 (COVID-19) pandemic has considerably differed worldwide. Generally, Asians are more inclined to wear face masks during disease outbreaks. Hong Kong has emerged relatively unscathed during the initial outbreak of COVID-19, despite its dense population. Previous infectious disease outbreaks influenced the local masking behaviour and response to public health measures. Thus, local behavioural insights are important for the successful implementation of infection control measures. This study explored the behaviour and attitudes of wearing face masks in the community during the initial spread of COVID-19 in Hong Kong. METHODS: We observed the masking behaviour of 10 211 pedestrians in several regions across Hong Kong from 1 to 29 February 2020. We supplemented the data with an online survey of 3199 respondents' views on face mask use. RESULTS: Among pedestrians, the masking rate was 94.8%; 83.7% wore disposable surgical masks. However, 13.0% wore surgical masks incorrectly with 42.5% worn too low, exposing the nostrils or mouth; 35.5% worn 'inside-out' or 'upside-down'. Most online respondents believed in the efficacy of wearing face mask for protection (94.6%) and prevention of community spread (96.6%). Surprisingly, 78.9% reused their mask; more respondents obtained information from social media (65.9%) than from government websites (23.2%). CONCLUSIONS: In Hong Kong, members of the population are motivated to wear masks and believe in the effectiveness of face masks against disease spread. However, a high mask reuse rate and errors in masking techniques were observed. Information on government websites should be enhanced and their accessibility should be improved.

Management of hepatocellular carcinoma after progression on first-line systemic treatment: defining the optimal sequencing strategy in second line and beyond.

Hepatocellular carcinoma (hcc) is one of the most common cancers in the world. It has a high mortality rate, especially when localized treatments fail. For about a decade, the only systemic treatment shown to improve survival was sorafenib. Recently, lenvatinib was found to be noninferior to sorafenib for overall survival, and combination atezolizumab-bevacizumab improved survival compared with sorafenib. Similarly, in the post-sorafenib setting, a number of recent positive clinical trials have been reported, and they indicate that regorafenib, cabozantinib, and ramucirumab are effective and safe in the second-line setting. With so many new options available, including immunotherapy, it is challenging to define the best sequence of systemic treatment for patients with hcc. In the present review, we introduce the current data for second-line systemic treatment and beyond in hcc. A treatment algorithm is also suggested, based on the best available evidence and expert opinion.

Oncology education for Canadian internal medicine residents: the value of participating in a medical oncology elective rotation.

Background: Despite the high incidence and burden of cancer in Canadians, medical oncology (mo) rotations are not mandatory in most Canadian internal medicine (im) residency training programs. Methods: All im residents scheduled for a mo rotation at 4 Canadian teaching cancer centres between 1 January 2013 and 31 December 2015 were invited to complete an online survey before and after their rotation. The survey was designed to evaluate perceptions of oncology, comfort in managing cancer patients, and basic oncology knowledge. Results: The survey was completed by 68 im residents pre-rotation and by 48 (71%) post-rotation. Cancer-related learning was acquired mostly from mo physicians in clinic (35%). Self-directed learning, didactic teaching, and resident or fellow teaching accounted for 31%, 26%, and 10% respectively of learning acquisition. Comfort level in dealing with cancer patients and patients at end of life improved to 4.0/5 from 3.2/5 (p < 0.001) and to 4.0/5 from 3.6/5 (p = 0.003) respectively. Mean knowledge assessment score improved to 83% post-rotation from 76% pre-rotation (p = 0.003), with the greatest increase observed in general knowledge of common malignancies. The 3 topics ranked as most important to learn during a mo rotation were oncologic emergencies, common complications of treatment, and approach to diagnosis of cancer. Conclusions: A rotation in mo improves the perceptions of im residents about oncology and their comfort level in dealing with cancer patients and patients at end of life. Overall cancer knowledge is also improved. Given those benefits, im residency programs should encourage most of their residents to complete a mo rotation.

Impact of country-specific EQ-5D-3L tariffs on the economic value of systemic therapies used in the treatment of metastatic pancreatic cancer.

BACKGROUND: Previous Canadian cost-effectiveness analyses in cancer based on the EQ-5D-3L (EuroQoL, Rotterdam, Netherlands) have commonly used U.K. or U.S. tariffs because the Canadian equivalent only just recently became available. The implications of using non-Canadian tariffs to inform decision-making are unclear. We aimed to reevaluate an earlier cost-effectiveness analysis of therapies for metastatic pancreatic cancer (originally performed using U.S. tariffs) with tariffs from Canada and various other countries to determine the impact of using non-country-specific tariffs. METHODS: We used tariffs from Canada, the United States, the United Kingdom, Denmark, France, Germany, Japan, the Netherlands, and Spain to derive EQ-5D-3L utilities for the 10 health states in the pancreatic cancer model. Quality-adjusted life years (qalys) and incremental cost-effectiveness ratios (icers) were generated, and probabilistic sensitivity analyses (psas) were performed. RESULTS: Canadian utilities are generally lower than the corresponding U.S. utilities and higher than those for the United Kingdom. Compared with the Canadian-valued scenarios, U.S. and U.K. estimates were statistically different for 3 and 9 scenarios respectively. Overall, 35% of the non-Canadian utilities (28 of 80) were significantly different, clinically, from the Canadian values. Canadian qalys were 6% lower than those for the United States and 6% higher than those for the United Kingdom. When comparing the qalys of each treatment with those of gemcitabine alone, the average percent change was +6.8% for a U.S. scenario and -7.5% for a U.K. scenario compared with a Canadian scenario. Consequently, Canadian icers were approximately 5.4% greater than those for the United States and 8.6% lower than those for the United Kingdom. Based on the psas and compared with the Canadian threshold value, the minimum willingness-to-pay threshold at which the combination chemotherapy regimen of gemcitabine-capecitabine is the most cost-effective is $5,239 less than in the United States and $11,986 more than in the United Kingdom. CONCLUSIONS: The use of non-country-specific tariffs leads to significant differences in the derived utilities, icers, and psa results. Past Canadian EQ-5D-3L-based cost-effectiveness analyses and related funding decisions might need to be re-visited using Canadian tariffs.

Oncology education in Canadian undergraduate and postgraduate medical programs: a survey of educators and learners.

BACKGROUND: The oncology education framework currently in use in Canadian medical training programs is unknown, and the needs of learners have not been fully assessed to determine whether they are adequately prepared to manage patients with cancer. METHODS: To assess the oncology education framework currently in use at Canadian medical schools and residency training programs for family (fm) and internal medicine (im), and to evaluate opinions about the content and utility of standard oncology education objectives, a Web survey was designed and sent to educators and learners. The survey recipients included undergraduate medical education curriculum committee members (umeccms), directors of fm and im programs, oncologists, medical students, and fm and im residents. RESULTS: Survey responses were received from 677 educators and learners. Oncology education was felt to be inadequate in their respective programs by 58% of umeccms, 57% of fm program directors, and 50% of im program directors. For learners, oncology education was thought to be inadequate by 67% of medical students, 86% of fm residents, and 63% of im residents. When comparing teaching of medical subspecialty-related diseases, all groups agreed that their trainees were least prepared to manage patients with cancer. A standard set of oncology objectives was thought to be possibly or definitely useful for undergraduate learners by 59% of respondents overall and by 61% of postgraduate learners. CONCLUSIONS: Oncology education in Canadian undergraduate and postgraduate fm and im training programs are currently thought to be inadequate by a majority of educators and learners. Developing a standard set of oncology objectives might address the needs of learners.

Cost-effectiveness of systemic therapies for metastatic pancreatic cancer.

PURPOSE: Gemcitabine and capecitabine (gem-cap), gemcitabine and erlotinib (gem-e), and folfirinox (5-fluorouracil-leucovorin-irinotecan-oxaliplatin) are new treatment options for metastatic pancreatic cancer, but they are also more expensive and potentially more toxic than gemcitabine alone (gem). We conducted a cost-effectiveness analysis of these treatment options compared with gem. METHODS: A Markov model was constructed to examine costs and outcomes of gem-cap, gem-e, folfirinox, and gem in patients with metastatic pancreatic cancer from the perspective of a government health care plan. Ontario health economic and costing data (2010 Canadian dollars) were used. Efficacy data for the treatments were obtained from the published literature. Resource utilization data were derived from a chart review of consecutive metastatic patients treated for pancreatic cancer at Princess Margaret Hospital, Toronto, Ontario, 2008-2009, and supplemented with data from the literature. Utilities were obtained by surveying medical oncologists across Canada using the EQ-5D. Incremental cost-effectiveness ratios (icers) were calculated. RESULTS: The icers for gem-cap, gem-e, and folfirinox compared with gem were, respectively, CA$84,299, CA$153,631, and CA$133,184 per quality-adjusted life year (qaly). The model was driven mostly by drug acquisition costs. Given a willingness-to-pay (wtp) threshold greater than CA$130,000/qaly, folfirinox was most cost-effective treatment. When the wtp threshold was less than CA$80,000/qaly, gem alone was most cost-effective. The gem-e option was dominated by the other treatments. CONCLUSIONS: The most cost-effective treatment for metastatic pancreatic cancer depends on the societal wtp threshold. If the societal wtp threshold were to be relatively high or if drug costs were to be substantially reduced, folfirinox might be cost-effective.

Generalizability of toxicity data from oncology clinical trials to clinical practice: toxicity of irinotecan-based regimens in patients with metastatic colorectal cancer.

BACKGROUND: The relevance of oncology trial results to clinical practice depends on whether the trial participants are similar to the actual population of patients receiving treatment for the malignancy and whether the patients are treated similarly in both circumstances. Chemotherapy treatments may be more toxic in patients of advanced age and poor performance status-patients typically excluded from clinical trials. METHODS: In a retrospective chart review that included all non-trial patients with metastatic colorectal cancer treated with irinotecan-based chemotherapy from January 2004 to September 2006 at our institution, we quantified and subsequently compared the toxicity rates of the irinotecan regimens in clinical practice with published toxicity rates from corresponding phase iii clinical trials. The primary endpoint was the incidence of grades 3 and 4 diarrhea. RESULTS: The study included 203 patients, and the irinotecan regimens considered included FOLFIRI [irinotecan, leucovorin, 5-fluorouracil (5fu)],IFL (bevacizumab, irinotecan, 5FU, leucovorin),XELIRI (capecitabine, 3-weekly irinotecan), andirinotecan monotherapy. The rates of grades 3 and 4 diarrhea for FOLFIRI, IFL, XELIRI, and irinotecan monotherapy in clinical practice were 10%, 15%, 17%, and 21% as compared with 10%, 23%, 20%, and 31% respectively in clinical trials. When only patients meeting trial performance status and age criteria were analyzed, the rates of grades 3 and 4 diarrhea by regimen were 11%, 20%, 19%, and 26% respectively. CONCLUSIONS: Overall, the toxicity rates for FOLFIRI and irinotecan monotherapy in non-trial patients were not statistically different from the rates quoted in published clinical trials.