Unification of Efforts to Improve Global Access to Cancer Therapeutics: Report From the 2022/2023 Access to Essential Cancer Medicines Stakeholder Summit.

PURPOSE: There is an urgent need to improve access to cancer therapy globally. Several independent initiatives have been undertaken to improve access to cancer medicines, and additional new initiatives are in development. Improved sharing of experiences and increased collaboration are needed to achieve substantial improvements in global access to essential oncology medicines. METHODS: The inaugural Access to Essential Cancer Medicines Stakeholder Meeting was organized by ASCO and convened at the June 2022 ASCO Annual Meeting in Chicago, IL, with two subsequent meetings, Union for International Cancer Control World Cancer Congress held in Geneva, Switzerland, in October 2022 and at the ASCO Annual Meeting in June of 2023. Invited stakeholders included representatives from cancer institutes, physicians, researchers, professional societies, the pharmaceutical industry, patient advocacy organizations, funders, cancer organizations and foundations, policy makers, and regulatory bodies. The session was moderated by ASCO. Past efforts and current and upcoming initiatives were initially discussed (2022), updates on progress were provided (2023), and broad agreement on resulting action steps was achieved with participants. RESULTS: Summit participants recognized that while much work was ongoing to enhance access to cancer therapeutics globally, communication and synergy across projects and organizations could be enhanced by providing a platform for collaboration and shared expertise. CONCLUSION: The summit resulted in new cross-stakeholder insights and planned collaboration addressing barriers to accessing cancer medications. Specific actions and timelines for implementation and reporting were established.

Treatment Access for Gastrointestinal Stromal Tumor in Predominantly Low- and Middle-Income Countries.

Importance: Gastrointestinal stromal tumor (GIST) is a rare cancer treated with the tyrosine kinase inhibitors imatinib mesylate or sunitinib malate. In general, in low- and middle-income countries (LMICs), access to these treatments is limited. Objective: To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs. Design, Setting, and Participants: This retrospective database cohort analysis included patients in 2 access programs administered by The Max Foundation: the Glivec International Patient Assistance Program (GIPAP), from January 1, 2001, to December 31, 2016, and the Max Access Solutions (MAS) program, January 1, 2017, to October 12, 2020. Sixty-six countries in which The Max Foundation facilitates access to imatinib and sunitinib were included. Participants consisted of patients with approved indications for imatinib, including adjuvant therapy in high-risk GIST by pathologic evaluation of resected tumor or biopsy-proven unresectable or metastatic GIST. All patients were reported to have tumors positive for CD117(c-kit) by treating physicians. A total of 9866 patients received treatment for metastatic and/or unresectable disease; 2100 received adjuvant imatinib; 49 received imatinib from another source and were only included in the sunitinib analysis; and 53 received both imatinib and sunitinib through The Max Foundation programs. Data were analyzed from October 13, 2020, to January 30, 2024. Main Outcomes and Measures: Demographic and clinical information was reported by treating physicians. Kaplan-Meier analysis was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). An imputation-based informed censoring model estimated events for patients lost to follow-up after treatment with adjuvant imatinib. Patients who were lost to follow-up with metastatic or unresectable disease were presumed deceased. Results: A total of 12 015 unique patients were included in the analysis (6890 male [57.6%]; median age, 54 [range, 0-100] years). Of these, 2100 patients were treated with imatinib in the adjuvant setting (median age, 54 [range 8-88] years) and 9866 were treated with imatinib for metastatic or unresectable disease (median age, 55 [range, 0-100] years). Male patients comprised 5867 of 9866 patients (59.5%) with metastatic or unresectable disease and 1023 of 2100 patients (48.7%) receiving adjuvant therapy. The median OS with imatinib for unresectable or metastatic disease was 5.8 (95% CI, 5.6-6.1) years, and the median TTD was 4.2 (95% CI, 4.1-4.4) years. The median OS with sunitinib for patients with metastatic or unresectable GIST was 2.0 (95% CI, 1.5-2.5) years; the median TTD was 1.5 (95% CI, 1.0-2.1) years. The 10-year OS rate in the adjuvant setting was 73.8% (95% CI, 67.2%-81.1%). Conclusions and Relevance: In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.

CML Outcomes and Care Delivery During the COVID-19 Pandemic in Low- and Middle-Income Countries.

PURPOSE OF REVIEW: The study aims to evaluate the impact of COVID-19 on the delivery of health care and services to patients with chronic myeloid leukemia in low- and middle-income countries (LMICs) accessing treatment through The Max Foundation. RECENT FINDINGS: An online survey was developed and sent via email to 527 partner physicians who had active patients under their care in July 2020, asking about the disruption of health services with multiple-choice answers or a five-point ordinal scale. Data from The Max Foundation's Patient Access Tracking System (PATS®) was analyzed to evaluate program performance in 2020 compared with 2019. PATS® is used to track key patient information and supply chain data to ensure robust reporting, quality assurance, and safety. Among the 111 physicians who responded (20% response rate), 48% reported that someone on their team had contracted COVID-19. A total of 95 (85%) physicians reported at least some disruption of services to patients due to COVID-19, with 29 (26%) reporting frequent or complete disruption. Almost all physicians in the South Asia and Asia Pacific regions reported disruption (96% and 95%, respectively), compared with three quarters of physicians in Latin America. Institutions overcame challenges using a variety of solutions including telemedicine (60%), electronic prescriptions (45%), home delivery via courier services (31%), government workers (9%), and dispensation coordination with regional hospitals (14%). The COVID-19 pandemic has disrupted services for CML physicians and patients worldwide. Overall, these disruptions did not appear to significantly affect The Max Foundation's ability to provide patients with access to treatment, as novel approaches in telemedicine, supply chain, and dispensing, as well as provision of guidance and support for physicians were utilized to overcame disruption of services.

Analysis of the gap in PCR monitoring availability for patients with chronic myeloid leukemia in 60 low- and middle-income countries.

PURPOSE: To estimate the resource gap in the polymerase chain reaction (PCR) monitoring for patients with chronic myeloid leukemia (CML) in low- and middle-income countries (LMICs). METHODS: We developed a model of demand and supply of PCR monitoring of CML patients in 60 LMICs. PCR testing was assumed to use Cepheid's GeneXpert® IV system. We included costs of GeneXpert® instruments, uninterrupted power supplies, warranties, calibration kits, test cartridges, and shipping. We calculated the country-specific monetary gap in PCR monitoring, stratified by country priority defined as the availability of tyrosine kinase inhibitors (TKIs) through The Max Foundation initiatives. RESULTS: The 5-year gap in PCR monitoring was $29.1 million across all countries, 22% ($6.4 million) in countries with all five TKIs available, 20% ($5.7 million) in countries with four TKIs available, 50% ($14.5 million) in countries with three TKIs available, 8% ($2.2 million) in countries with two TKIs available, and 1% ($0.3 million) in countries with one TKI available. The gap was highest in South Asia (52%; $15.1 million) and lowest in Latin America (6%; $1.9 million). Excluding labor costs, the bulk of the resource needs (86%; $25.2 million) were for procurement of BCR-ABL cartridges. CONCLUSION: Removing the 5-year gap in PCR monitoring capacity for CML in LMICs will require the mobilization of significant resources and will likely lead to better treatment outcomes and reduced treatment costs through optimization of treatment, discontinuation of therapy in appropriate patients, and facilitation of clinical research. Development of streamlined monitoring guidelines for resource-limited countries should be considered.

The survival of patients enrolled in a global direct-to-patient cancer medicine donation program: The Glivec International Patient Assistance Program (GIPAP).

BACKGROUND: The Glivec International Patient Assistance Program (GIPAP) is a unique direct-to-patient program that provides imatinib (Glivec) at no cost to eligible patients in low- and middle-income countries (LMICs) with chronic myelogenous leukemia (CML) or gastrointestinal stromal tumor (GIST). This paper analyses the output, outcome and impact of the program between 2001 and 2014 using the data collected by the Max Foundation. METHOD: We extracted data on GIPAP patients' country of residence, sex, diagnosis, date of enrollment in GIPAP, age at enrollment, case closure date, and reason for closure from The Max Foundation database covering the period 2001 to 2014. We used Kaplan-Meier method to assess the survival rate of patients in GIPAP and used the proportional hazard regression model to estimate the effect of different variables on patients' survival. FINDINGS: About 63,000 GIPAP patients in 93 countries received over 71 million defined daily doses (DDD) of imatinib between 2001 and 2014. Our analysis showed that GIPAP patients had a 5-year survival rate of 89% which compares favorably to survival in high income countries despite the challenges of delivering cancer care in LMICs. Age at enrollment into the program, sex, duration between diagnosis and enrollment into program, year of enrollment, and patients' diagnosis (CML vs non-CML) were factors that influenced survival. INTERPRETATION: The GIPAP program has improved the survival of CML and GIST patients in LMICs, most of whom would not have had access to imatinib in the absence of the donation and therapeutic support of the program. FUNDING: This work was funded as part of Access Accelerated case studies. Access Accelerated is an initiative of more than 20 global biopharmaceutical companies in partnership with the World Bank and Union of International Cancer Control that seeks to reduce barriers to prevention, treatment and care for non-communicable diseases in LMICs.

Meeting the needs of CML patients in resource-poor countries.

Subsequent to the development and global availability of BCR/ABL-targeted tyrosine kinase inhibitors (TKIs), the prognosis of patients with chronic myeloid leukemia (CML), at least those in the chronic phase, has markedly improved, and in the developed world, the average lifespan of these patients is now close to that of age- and sex-matched subjects without the disease. However, the situation in low- and middle-income countries (LMICs) may not be so rosy. Many important differences in hematological cancers, including CML, have been highlighted in various publications in LMICs vs developed countries. These include differences in incidence and prevalence rates, age and stage of disease at diagnosis, response rates, and survival. Some of the possible reasons proposed for these are varying socioeconomic milieu (impacting availability of effective drugs and essential monitoring), environmental factors (mainly exposure to viral infections and pesticides), nutritional factors with interplay of malnutrition and diet on drug absorption and blood levels, and possible unknown genetic factors. Although generic first-generation TKIs (imatinib) are available in many parts of the world, several challenges remain in providing optimal treatment to patients with CML in resource-poor countries. Some of these include availability of optimal and high-quality BCR/ABL testing, availability and expense related to use of second- and third-generation TKIs (nilotinib, dasatinib, bosutinib, and ponatinib) and hematopoietic stem cell transplantation, issues with compliance and toxicities of drugs, and ensuring a minimal standard-of-care treatment and monitoring for every patient diagnosed with CML. For the purpose of this article, the more objective country label-LMIC-coined by the World Bank will be used (gross national income per capita between $1026 and $3995; World Bank, June 2019). Some of these issues will be discussed in this article in greater detail by experts in the field in 3 different but interconnected sections.

A pharmacovigilance system for treatment access and medical donation programs: The Max Foundation experience.

BACKGROUND: Cancer is a major burden of disease in low- and middle-income countries (LMICs) yet financial barriers limit access to life-saving oncology drugs. Medical donation and other drug access programs can help improve patient access to essential medicines, such as quality assured oncology drugs in LMICs. However, there are no published examples of the conduct of pharmacovigilance with donated medical products intended for use in LMICs where pharmacovigilance is weak. We describe a partnership between a pharmaceutical company and a non-governmental organization as a case example that addresses the challenges in performing pharmacovigilance with donated medicines in LMICs. The Max Foundation's direct to patient model is designed to improve global access to quality assured oncology drugs through access programs such as the Glivec® (generic name: imatinib) International Patient Assistance Program (GIPAP). RESULTS: Between 2013 and 2016, in the course of managing the GIPAP program, The Max Foundation was made aware of 13,039 instances of adverse events (AEs). These AEs were reported to The Max Foundation by physicians, patients, and caregivers. The Max Foundation reported these AEs to Novartis through the AE reporting tool within its Patient Assistance Tracking System (PATS). Physicians were the reporters for 58% of the AEs while the remainder of the AEs were reported directly by patients or caregivers. The overall rate of reported AEs remained relatively steady for the years 2013 through 2016 at 92, 95, 86, and 97 AEs reported per 1000 persons who received Glivec® per year, respectively. The vast majority of adverse events (85%) were reported from countries where The Max Foundation has a MaxStation, i.e., where The Max Foundation staff interact directly with physicians and patients at clinics or over the phone. AE reporting rates were consistently higher in all years studied from countries where The Max Foundation has a MaxStation. While India accounted for the largest number of reported adverse events in 2016 (1990), Bolivia had the highest rate of reported adverse events at 484 AEs per 1000 patients. CONCLUSIONS: International patient assistance programs that provide access to medicines can have an important role in assisting pharmaceutical companies in fulfilling their pharmacovigilance obligations. Adverse event information collected through PATS can potentially contribute to the overall body of knowledge on the safety of medicinal products.

Novel Humanitarian Aid Program: The Glivec International Patient Assistance Program-Lessons Learned From Providing Access to Breakthrough Targeted Oncology Treatment in Low- and Middle-Income Countries.

Imatinib was the first targeted therapy approved for the treatment of cancer. With its approval, it was immediately clear to Novartis that this breakthrough therapy would require an innovative approach to worldwide access, with special consideration of low- and middle-income countries. Lack of government reimbursement, universal health care, or health insurance coverage, few trained specialty physicians or diagnostic services, and poor health care infrastructure were, and continue to be, contributing barriers to access to treatment in low- and middle-income countries. The Glivec International Patient Assistance Program (GIPAP) is an international drug donation program established by Novartis Pharma AG and implemented in partnership with The Max Foundation, a nonprofit, nongovernmental organization. GIPAP was established in 2001, essentially in parallel with the first approval of imatinib for chronic myeloid leukemia. Since 2001, GIPAP has made imatinib accessible to all medically and financially eligible patients within 80 countries on an ongoing basis as long as their physicians prescribe it and no other means of access exists. To date, more than 49,000 patients have benefited from GIPAP, and 2.3 million monthly doses of imatinib have been approved through the program. GIPAP represents an innovative drug donation model that has set the standard for access programs for other targeted or innovative therapies. The purpose of this article is to describe the structure of GIPAP, as well as important lessons that have contributed to the success of the program. This article may assist other companies with the development of successful and far-reaching patient assistance programs in the future.

International patterns of childhood chronic myeloid leukemia: comparisons between the United States and resource-restricted nations.

BACKGROUND: Chronic myeloid leukemia (CML) is a rare disease in children and represents approximately 2% of all childhood leukemia. This results in difficulty creating large cohorts of patients for pediatric CML research. The Glivec International Patient Assistance Program (GIPAP) is a patient-access program sponsored by Novartis Oncology and administered by The Max Foundation (MAX) that provides imatinib free of charge to patients in resource-restricted countries who are not able to afford this treatment. PROCEDURES: GIPAP highlights a cohort of children (n = 3,188) with CML that provides novel insight into international trends in diagnosis, treatment, and survival. These trends can be compared to outcomes in developed nations to crudely assess the impact of an extended access program for CML treatment such as GIPAP. RESULTS: Overall survival values for children treated for CML within the GIPAP (89%) suggest that imatinib is very effective in middle and low-income countries. CONCLUSIONS: This may allow for increased international awareness within the scientific community to consider possible reasons for the differences in overall survival in pediatric CML within the United States versus other nations with fewer resources.

Regional variations in age at diagnosis and overall survival among patients with chronic myeloid leukemia from low and middle income countries.

INTRODUCTION: The epidemiology of chronic myeloid leukemia (CML) in low and middle income countries is limited. As a result, we analyzed a contemporary cohort of patients from low and middle income countries treated with Imatinib through The Glivec(®) International Patient Assistance Program (GIPAP). METHODS: Generalized estimating equations (GEE) and Kaplan-Meier estimation were utilized to test for regional variations in age at diagnosis and overall survival among 33,985 patients from 94 countries. RESULTS: Patients participated from Asia (79.2%), Africa (9.4%), Latin America (8.7%) and Southern/Eastern Europe (2.5%). Sixty-one (61.2%) percent were male. Mean age at diagnosis was 38.5 years (9.4% <20 years and only 4.7% ≥65 years). Using GEE, Asians were youngest (38.3 years), followed by Africans (39.5 years), Southern/Eastern Europeans (41.1 years) and Latin Americans (41.3 years; p < 0.0001). Diagnoses were predominately in chronic stage (78.3%). In 2002, 85.2% of patients had a delay in treatment >1 year; decreasing to 15.5% in 2010 (p < 0.0001). The 3-year overall survival probability was 89.4% (95% CI, 88.9-89.9). In multivariate analysis, risk of death increased among patients 65 years or older at diagnosis (p < 0.0001), time from diagnosis to treatment >1-year (p < 0.0001), diagnoses in the accelerated or blast crisis (p < 0.0001), initial dose of Imatinib >400 mg (p < 0.0001) and among Latin Americans and Africans (p < 0.0001). CONCLUSION: The GIPAP cohort is the largest series of patients with CML described from low and middle income countries. Differences in age at diagnosis and overall survival exist within and between regions. Additional epidemiological studies should be conducted to assess for possible environmental factors associated with the earlier age at onset.

Maximize Life Global Cancer Awareness Campaign: improving the lives of cancer patients while increasing global awareness of their needs.

In October 2010 The Max Foundation, in partnership with 30 cancer patient associations in emerging countries, organized a global cancer awareness campaign. The aims of the campaign were: (i) to increase awareness of the needs of people living with cancer in developing countries; (ii) to increase local visibility of patient associations in their countries; (iii) to collect more than 10,000 signatures to the World Cancer Declaration (WCD); and (iv) to improve the lives of cancer survivors by providing them with an opportunity to express their feelings about the disease. The campaign was developed as a global effort, to be implemented by local patient associations through their volunteer survivors and caregivers. The methodology at the global level included developing the framework, branding, and communication tools, while making available limited funding and heavy logistical support. Local patient associations were encouraged to adapt the initiative to a culturally accepted format. Key elements of the campaign were the mix of low tech and high tech elements to allow low tech populations to participate while promoting the initiative using social media and high tech tools. Additionally, the participation of survivors and caregivers ensured the campaign provided immediate benefit to cancer patients. Finally, the addition of the World Cancer Declaration provided a strong unifying component. More than 60 events were held in 31 countries around the world, collecting more than 13,000 signatures to the World Cancer Declaration and a similar number of support messages to cancer survivors representing 84 countries. Local events gained local media visibility in many countries, and the campaign was promoted in multiple international forums and Web sites. This initiative involving mobilization of volunteers and the development of a global initiative as a grassroots movement taught important lessons on media outreach and selection of leaders for a cancer awareness campaign.

Benefits of global partnerships to facilitate access to medicines in developing countries: a multi-country analysis of patients and patient outcomes in GIPAP.

BACKGROUND: Access to medicines in developing countries continues to be a significant problem due to lack of insurance and lack of affordability. Chronic Myeloid Leukemia (CML), a rare disease, can be treated effectively, but the pharmaceutical treatment available (imatinib) is costly and unaffordable by most patients. GIPAP, is a programme set up between a manufacturer and an NGO to provide free treatment to eligible CML patients in 80 countries worldwide. OBJECTIVES: To discuss the socio-economic and demographic characteristics of patients participating in GIPAP; to research the impact GIPAP is having on health outcomes (survival) of assistance-eligible CML patients; and to discuss the determinants of such outcomes and whether there are any variations according to socio-economic, demographic, or geographical criteria. METHODS: Data for 13,568 patients across 15 countries, available quarterly, were analysed over the 2005-2007 period. Ordered Probit panel data analysis was used to analyze the determinants of a patient's progress in terms of participation in the programme. Four waves of patients entering quarterly in 2005 were used to evaluate patient survival over the sample period. RESULTS: All patients in the sample are eligible to receive treatment provided they report to a facility quarterly. 62.3% of patients were male and 37.7% female. The majority (84.4%) entered during the chronic phase of the disease and their average age was 38.4 years. Having controlled for age, location and occupation, the analysis showed that patients were significantly much more likely to move towards a better health state after receiving treatment irrespective of their disease stage at the point of entry to the program (OR = 30.5, alpha = 1%); and that the larger the gap between diagnosis and approval for participation in the program, the more likely it is that patients' condition deteriorates (OR = 0.995, alpha = 1%), due to absence of treatment. Regressions to account for the effect of large countries (India, China, Pakistan) did not show any important differences when compared to the remaining countries in the sample. Survival analysis shows that at least 66 percent of all patients that entered the program in 2005 were alive and active by the end of 2007. CONCLUSIONS: GIPAP has a significant positive effect on patient access to important medicines for a life threatening condition such as CML. It impacts both the progress and phase of the disease and leads to a high survival rate. Overall, it sets a good example for access to treatment in developing countries, where such programmes can substitute or complement local efforts to provide care to eligible patients.