Impact case study database

The SCOT and the IDEA trials have been highlighted through international guidelines and within the professional community as a landmark moment for oncologists and their patients. The studies demonstrated the effectiveness of 3 months of adjuvant chemotherapy for some patients with CRC (with reduced side effects) and the economic benefits of a shorter regimen. The clinical findings reported by these trials have led to a new global standard for most patients who are suitable to treat with CAPOX, particularly those with low-risk stage 3 disease; this new standard balances the efficacy of a chemotherapy regimen with toxicity and quality of life, depending on patients’ tolerance and attitude to their disease.

Dissemination and discussion in the clinical community

In 2017, the SCOT and IDEA trial results were presented at the American Society for Clinical Oncology (ASCO) conference, a leading forum for oncologists worldwide consisting of 35,000 medical professionals, and at the 2017 European Society for Medical Oncology (ESMO) congress, which brings together over 15,000 medical professionals. At ESMO, a Special Session debate brought together the SCOT and IDEA trial leads with external experts and a clinical audience to clarify the potential impact of these results on clinical practice and to achieve a more meaningful interpretation of the results. The panel agreed on the value of CAPOX for 3 versus 6 months in low-risk stage III patients, given the increased quality of life [5.A]. Given that 92% of oncologists in a recent survey identified conferences as a key influence in their practice, the presentation of the SCOT and IDEA trial findings at these conferences likely stimulated discussion and considerations of practice within the CRC community [5.B]. An important and unanticipated piece of knowledge generated from post-hoc studies within both SCOT and IDEA is stage III risk stratification (into ‘low’ and ‘high’) which didn’t exist before. Many clinicians have adopted this risk stratification into their practice [5.B].

Impact on clinical guidelines now reflect a short-course treatment option

Updates to the preeminent clinical guidelines used by UK and international clinicians provide new options for treating low- and high-risk stage III CRC. We know that from a recent survey of this clinical community that 87% of clinicians treating CRC patients in the adjuvant setting use guidelines to inform treatment decisions, citing ESMO, ASCO, NCCN and NICE as preeminent in this regard [5.B].

• In September 2019, ESMO issued an eUpdate to their 2013 early colon cancer guidelines, citing IDEA data to recommend that duration of oxaliplatin-based adjuvant treatment for stage III colon cancer may be tailored to 3 months for CAPOX (for patients with low risk T1–3 N1 disease), level II B [5.C]. They also recommended, for the first time, that oncologists consider using a 3-month CAPOX regimen for high-risk, stage II colon cancer, based on the pre-planned sub-group analysis of IDEA data that drew heavily from SCOT trial data [3.5]. This is an important consideration given the benefits that oxaliplatin therapy can have for patients with high-risk stage II CRC, and addresses uncertainty among oncologists—25% of survey respondents were unsure whether 3-month CAPOX could be considered.

• In June 2019, ASCO published a clinical practice guideline to specifically address the duration of oxaliplatin-containing adjuvant therapy [5.D]. This guideline offers three recommendations: 1) that high-risk (T4 and/or N2) stage III CRC patients are offered a 6-month therapy; 2) that low-risk patients (those with T1-3 and N1 stage tumours) are given a choice of 3-month or 6-month therapy; and 3) that a shared decision-making approach with patients should be used that reflects patient characteristics and preferences, and the risks and benefits of treatment duration.

• In 2018, the National Comprehensive Cancer Network ( NCCN) —a consortium of 23 US centres of clinical excellence in cancer care— updated its colon cancer guidelines to recommend that the preferred treatment for low-risk stage III CRC include CAPOX for 3 months or FOLFOX for 3–6 months; and for high-risk CRC, CAPOX (3–6 months) or FOLFOX (6 months) [5.E].

• In January 2020, NICE published a new guideline (NG151 Colorectal cancer) that specifically addressed the optimal duration of adjuvant chemotherapy for CRC [5.F]. Drawing on the SCOT and IDEA trials, the committee recommended 3 months of CAPOX chemotherapy for both low- and high-risk CRC patients. The review concluded there was strong cost-effectiveness evidence to support the recommendation, citing the UofG study [3.3] as being directly applicable and of high quality. NICE also recommended FOLFOX for 3 to 6 months, with duration determined through individual consultation with those patients not suitable for 3 months of CAPOX, taking into account the benefits and short- and long-term harms of each option. On the basis of the SCOT trial, which was the only study to recruit a significant number of patients with rectal cancer, the committee also extended these recommendations to those rectal cancer patients who had not received preoperative, long-course chemotherapy.

Impact on clinical practice

Around 64% of all stage-III CRC patients are eligible for chemotherapy. In the UK, this equates to ~6,300 patients, with an equal split between low-risk (T1–3/N1) and high-risk (T4/N2) disease. In April 2019, 95% of international clinicians and 99% of UK clinicians who provide adjuvant doublet chemotherapy to CRC patients reported being aware of clinical trials on optimising chemotherapy duration in this setting, citing either SCOT (more common in UK) or IDEA. Around 92% self-reported changing their practice in line with these studies’ findings, with 98% of these clinicians doing so specifically when treating ‘low risk’ stage III disease [5.B]. Of UK clinicians surveyed (n=141), 92% treat patients with rectal cancer and 58% use the same treatment strategy as for CRC [5.B]. Practice change is also evident within the Beatson West of Scotland Cancer Care Centre, which serves 60% of Scotland’s population. The proportion of patients within this region receiving more than 3 months of CAPOX treatment decreased substantially since the SCOT trial results were reported (from 84% pre-SCOT to 20% post-SCOT) with a clear change in trend from June 2017 onwards, reflecting rapid translation of trial evidence into practice [5.G]. This change to a 3-month treatment duration is also apparent in prescribing data from across Scotland [5.G].

The National Cancer Research Institute (NCRI) Colorectal Cancer Clinical Studies Group (CRC-CSG) comprises senior clinicians and patient representatives with a broad overview of UK practice in CRC. They stated, ‘ there has been a nationwide shift in prescribing a shorter duration of adjuvant doublet chemotherapy (CAPOX) for patients with low-risk stage III colon cancer. Using a shorter duration of treatment (3 months versus 6 months) for these patients has also had an immediate capacity impact at oncology outpatient departments and chemotherapy units across the UK, allowing appointments and chair time to be made available for treatment of other patients. For those patients with colorectal cancer who receive a shorter duration of treatment, a reduction in toxicity, especially peripheral neurotoxicity, has already been seen’ [5.H]. The CRC-CSG also acknowledged that, ‘ a shorter duration of doublet treatment (CAPOX) will likely be included as a new standard treatment for many patients receiving adjuvant treatment for CRC in future trials’. A reduction in toxicity also makes it possible to include additional combination therapies (e.g. immunotherapies) concurrently, increasing their curative potential [5.H].

Impact on patient quality of life

Neuropathy is the primary, long-term adverse effect of chemotherapy that has a significant negative impact on patients’ lives. However, peripheral sensory neuropathy is measurably reduced in patients receiving a shorter duration of treatment. In the UK, if ~3,630 patients per year agreed to a 3-month treatment regimen for stage III disease, 1,198 fewer patients are likely to experience grade 2 (moderate) or more severe neuropathy. These levels of neuropathy impede daily life (preparing meals, shopping, managing money) and work, and can persist for up to 5 years. A shorter course of chemotherapy also means less diarrhoea (a 40% reduced incidence has been reported in a 3-month therapy population [3.2]), as well as a lower incidence of fatigue, neutropenia, thrombocytopenia, nausea and hand-foot syndrome, fewer doctor appointments, blood draws and less time away from work/social interactions.

Impacts on healthcare and societal costs

The treatment costs accrued during the first year of a CRC diagnosis are greater than those accrued for other common cancers, such as breast, lung, and prostate. The total economic burden of CRC in the USA alone is estimated to be around USD39 billion. A shorter treatment duration will, on average, halve drug costs, as well as reducing administrative costs and the costs of treating adverse effects. The estimated costs saved in the UK ultimately depend on treatment choice, but the UofG health economic analysis put NHS cost savings at GBP4,881 per patient per year (or GBP3,853 for CAPOX and GBP6,481 for FOLFOX, with two-thirds of patients treated with CAPOX) [3.3]. A budget impact analysis calculated NHS savings over two years at GBP42 million [5.I]. This assumes that 64% stage III CRC patients receive adjuvant chemotherapy and 55% practice change across the whole stage III population who get chemotherapy. The budget impact analysis over a 5-year basis performed for SCOT-participant countries amounts to savings of around USD151 million: Australia (USD25 million), Denmark (USD7 million), New Zealand (USD4 million), Spain (USD44 million), Sweden (USD10 million) and UK (USD61 million) [5.I]. Furthermore, there are substantial potential savings in societal costs—defined as productivity loss from time away from work during chemotherapy treatment in patients of working age, plus the travel costs incurred by patients. During year 1 of treatment, extended over a 5-year basis, societal savings are nearly equal to the healthcare savings [5.I].