Sample demographics

64/114 applicants were selected to participate. 21/64 ineligible participants were subsequently excluded following screening. 7/43 who were invited to attend a FGD did not attend. Between January and May 2023 7 FGDs were conducted with 36 participants (3 FGDs for RCC, 3 FGDs for melanoma and 1 for carers). 5 participants from the first FGD (prior to the implementation of the screening video call) were excluded from the analysis as they did not meaningfully contribute to the discussion. The characteristics for the 31 participants included in the analysis are outlined in Table 1. Only 5 participants (2 RCC, 3 melanoma) had previous experience of taking part in a clinical trial.

Table 1 Participant characteristics.Findings

Participants’ perspectives on ICI optimisation were grouped into three themes: (1) “Treatment and clinic visits provide reassurance”, (2) “Assessment of personal risk versus benefit” and (3) “Pre-existing experience and beliefs about how treatment and trials work”. Themes were further divided into subthemes (see Fig. 2). Participants are described by a study ID number, with the preface M for participants with melanoma, R with RCC, and C for carers. Where participants with previous trial experience are quoted, this is indicated following the quote; all other quotes are from participants without previous trial experience.

Fig. 2

Patient perspectives on ICI optimisation themes and subthemes.

Theme 1: Treatment and clinic visits provide reassurance

One of the main aims of ICI optimisation trials is to improve HRQoL, assuming that a reduction in treatment visits would be desirable for patients. However, in this study, many participants reported that they found attending hospital for treatment or clinic visits reassuring, suggesting that reducing hospital visits may not necessarily improve HRQoL.

Subtheme 1: Attending hospital can be a positive experience

Patients receiving ICI reported attending for treatment allowed them to connect with others who were in a similar situation, giving a sense of community and providing support. Some participants described this as particularly beneficial during the COVID-19 pandemic when there was a reduction of in-person support services. Some participants also welcomed the opportunity to unwind and disconnect from external pressures.

“It’s funny because you would think it’s a depressing time, but actually there is a lot of camaraderie there and they’re really looked after by the teams.” (C2)

Subtheme 2: Stopping treatment is psychologically challenging

Some participants who had stopped treatment reported anxiety about not receiving treatment and feeling abandoned.

“Well, I found it really hard when I had to stop [treatment] after four [cycles]. From the psychological point of view, I felt, you know, this is just me and you know the gods, really.” (M4)

Participants expressed concern about a lack of monitoring and contact with their medical team when they stopped treatment, prompting feelings of worry and isolation.

“When your treatment comes to an end, you feel you’re in a black hole because whilst you’re on treatment, you’re being monitored, you’re being looked after and sort of at the end there’s nothing there.” (C5)

Subtheme 3: Dose or interval optimisation as a way of enabling treatment to continue for longer

When asked about their preferred optimisation approach, most participants preferred dose reduction or extending the interval between treatments over early cessation as they did not want to discontinue treatment and the associated monitoring. Several participants found reducing the dose or extending the interval between treatments attractive, as they felt these dosing schedules would be more tolerable and allow them to continue their overall treatment for longer.

“If I had been offered a lesser dose as a trial or a bigger gap to recover in the meantime that would have been terrific for me because it was literally all or nothing and I ended up with nothing. (M6)

Subtheme 4: Levels of clinical review on trial impacts views on taking part

Many participants found frequent contact with their specialist team reassuring, particularly early in their diagnosis. Lack of contact with their medical team may be detrimental psychologically.

“I quite like the idea that I go to hospital once a month. It isn’t a drag for me at all to have blood tests, chat with my oncologists or the nurse. You know, I feel like they’re keeping a watchful eye on me. If I didn’t go in for two months, I think I would start wondering what, you know, if everything is OK.” (R3)

ICI are typically administered as intravenous infusions every 2–6 weeks. Many participants wanted reassurance that if they received treatment less often, or stopped treatment, they would still receive regular monitoring from their medical team. Most reported having a telephone consultation in between treatment visits would provide adequate reassurance. Participants also felt it was important to have the option to resume standard of care (SOC) treatment if their cancer progressed and that this should be communicated clearly when they were considering whether to enrol.

“If you’re sort of carefully monitored thereafter. That would be crucial, I think.” (M7)

“As somebody said earlier, nobody knows the exact way of doing things and if you say that, OK, we stop [treatment] and it starts growing again, we’ll put you back on it. I’d feel reasonably comfortable about that.” (R8)

Some participants felt taking part in a clinical trial would increase the monitoring and input from medical staff in comparison to receiving treatment outside of a clinical trial and this would encourage them to take part.

“I’ve been on the … trial, so that was my only experience of any oncology treatment. So my first experience was I was given a research nurse and I was given access to this research nurse and my bloods were done regularly. I could have a sort of personal hotline to her, but at the time the care and attention that you get when you’re on a trial as opposed to [SOC] and I’m not saying that the care is inferior on the NHS, but it definitely is different being on a trial and not being on a trial.” (R9 – previous clinical trial experience)

Theme 2: Assessment of personal risk versus benefit

All participants reported they would prefer to receive optimised treatment if these regimens were proven to be equally as effective within a clinical trial. However, participants differed in their views about whether they would participate in an ICI optimisation trial. An ideal type analysis was conducted to determine which factors influenced participants’ views (see supplementary materials for optimal cases). This suggested that people’s willingness to participate was influenced by four main personal factors which participants used to assess the personal risk versus benefit of participating: response to treatment, prior toxicity, travel time to receive treatment/unable to drive and employment status. Of these factors, the most important were response to treatment and prior toxicity. Age, gender, whether participants had dependents and prior participation in a clinical trial did not appear to influence decision making.

Response to treatment

In general, participants were more positive about participation when they had experienced a good response to treatment, particularly if it was a complete response. Many participants indicated that they would be reluctant to participate in an early cessation trial unless they had a complete response.

“Personally, if the scan was clear, I wouldn’t have a problem with it [enrolling in an early cessation trial]. If the scan wasn’t clear, I’d be very reluctant to come off. If it was working, but not to the point of clear, I wouldn’t want to be coming off it after a year. Even with the chance of going back on it.” (R10)

Prior toxicity

Although many of the participants who responded well to treatment were positive about participating in an ICI optimisation study, others were reluctant to change the dose or schedule of a treatment they perceived was working well for them. This was particularly evident in those who were tolerating treatment well with minimal toxicity.

“I was doing well with minimal side effects… If it’s not broke, don’t fix it.” (M12)

In contrast, participants who experienced toxicity were more motivated to participate, as the primary driver for participating in an ICI optimisation trial was a potential reduction in toxicity.

“You know, if it’s still going to sort of do the job, but it’s not going to send the liver mad then I would want a bit of that.” (R10)

“My thoughts are more to do with, I think, management of side effects [rather than logistical benefits]. We did have a conversation about having a shorter period on nivolumab. I know that there is a trial run at [cancer centre] I think that runs that basically you can have a nivolumab for a year instead of two and then you’re being monitored and at the time we were willing to do that. We were actually welcoming the opportunity.” (C38)

Travel time to receive treatment and employment status

Some participants felt that attending less often for treatment would have logistical benefits, including spending more time with family, spending less time travelling to hospital and minimising the impact of treatment on work. Participants who had to travel long distances for treatment or were unable to drive felt that this would be much more beneficial than participants who had a short commute to receive treatment.

“I had brain metastases from the minute I was diagnosed, I’m not allowed to drive. So getting to the hospital for the blood tests and the treatment etcetera becomes sort of a fairly major undertaking… So it means that my partner’s disrupted from work. I’m disrupted from work and then, you know, it adds to the time frame because I can’t just jump in the car and drive there.” (M4)

Views on the balance of risk versus benefit changed over time

Most participants felt that their perception of personal risk and benefit changed over time. Many reported feeling fearful after their diagnosis, and as a result their primary focus was on controlling the cancer. Over time, participants whose cancer responded to treatment described a decrease in anxiety. Furthermore, most participants reported after initiating treatment they gained a better understanding about how treatment worked, and more insight into the implications of any side-effects that occurred. In these patients, their focus shifted from purely controlling the cancer to managing side effects and optimising HRQoL. This change in focus affected their personal assessment of risk and benefit and impacted their views about taking part in an ICI optimisation trial.

“Yeah. It’s like priorities, isn’t it? The priority is to hit it hard. You’ll put up with the rest of it. And then there’s a point where actually the priority is now the side effects.” (R14)

Theme 3: Pre-existing experience and beliefs about how treatment and trials work

Many participants had pre-existing beliefs about how treatment and trials work. This included the belief that more treatment would result in better disease control or that treatment should be tailored to the individual. Some participants also had the pre-existing belief that trials were a last resort when all other treatments had failed. These beliefs affected the acceptability of ICI optimisation trials.

Subtheme 1: Belief that more treatment is better

Most participants reported a pre-existing belief that the doses of treatment directly correlate with effect. Many participants translated their existing knowledge of other anticancer therapies, including chemotherapy and targeted therapies, into their understanding of ICI. Despite a presentation at the start of the FGD which outlined the mechanism of action of ICI and the evidence of overtreatment, most participants said they instinctively felt that higher doses of ICI would result in better disease control. This pre-existing belief made them less likely to agree to participate in an ICI optimisation trial, as they felt less treatment would be less effective at controlling the cancer.

“Logically there’s no reason why more grunt [treatment] should work, but instinctively, that’s what you think.” (R15)

“Look, I can remember looking up at the bag and thinking, oh, there’s a little bit left in there and telling the nurse there’s a bit in there. Can you just wiggle it in? I want as much in me as possible.” (R16)

Many participants reported that they found it difficult to understand how ICI worked, particularly when they were first diagnosed, which made it challenging to understand the logic for receiving less treatment.

“Immunotherapy is still a really weird thing for people, I think to get to grips with and understand how it works… I really struggled with the concept of it at the beginning.” (M4)

Most participants felt that patients would be more likely to consider participating in an ICI optimisation trial if they received clear communication from the oncology team explaining the scientific rationale. Importantly, this would need to include an explanation of the mechanism of action to emphasise that ICI do not result in the same dose-effect relationship we see with other treatments. A clear and appropriately pitched summary of the evidence supporting giving less ICI would be crucial.

“But isn’t some of this kind of about education to people, you know, before they started immunotherapy, if it was properly explained how it worked, and the fact that the current dosing is random. I mean, that’s the thing they just threw everything at it as often as possible because that was, you know, it’s what you did with chemo. And so, if that was what was translated across before you started this, someone sort of explained, then people would start from a different place with it or would understand we’re all being completely over medicated.” (M18 – previous clinical trial experience)

In contrast, some participants felt that they would not be able to process information about ICI and the logic of receiving optimised treatment at the time of diagnosis or during the early stages of their treatment as they were in a state of shock. Their decision making would be driven by emotions, and they may be too anxious to participate in an ICI optimisation trial.

Subtheme 2: Treatment should be personalised to the individual

Many participants had the belief that treatment dosing schedules should be personalised to the individual, for example doses based according to weight or other factors. Hypothetical trial designs that employed a personalised approached to optimise the dose and schedule of ICI were discussed. For example, trial designs which used therapeutic drug monitoring to measure ICI drug concentrations and formulate personalised treatment plans. Most participants felt this made intuitive sense and were very positive about taking part in a trial with a ‘personalised’ design.

“Everybody is different, and everybody reacts differently to treatment. Everybody’s cancer is different. And so why should everyone be getting exactly the same standard treatment? And it makes sense to personalise it. And the less treatment you have to have is a benefit. So if you’re saying, the drugs are still in your system, still working, why give more when you don’t need them?” (M19)

Subtheme 3: Trials are a last resort

Many participants who had not previously taken part in a clinical trial had the preconceived idea that trials were a last resort when all other treatments had failed. Consequently, some participants felt approaching patients about clinical trials early on in their diagnosis had the potential to be perceived negatively, the implication being that no other treatment options were available. Clearly communicating the nature of ICI optimisation trials and ensuring patients are aware of subsequent available treatments and trials should mitigate this concern. Providing general information on the role and nature of clinical trials may also help address the misconception of trials as a last resort.

“Like the whole concept of a trial has something of a ring of last chance saloon about it doesn’t it?” (M11)

“I’m getting the impression that literally the first time that people talk about trials is when everything has failed, and you are out of options and you’re suddenly scarpering for what do I do next? And then what I find is in those groups when I’m talking to patients is they start asking strangers. Does anybody know about any trials?” (C38)