ASCO 2023: Successes, failings, and cowboy boots

?Chicago feels a little different this year. The train ride from the airport to the city had a notable splash of youth and anticipation. I thought, perhaps, it was the joy and colour associated with the first day of #pridemonth, but this crowd was a little too young, a little too female, and a little too sparkly. The lift (or, elevator) at my hotel was packed; 20 or more people. I have a personal hatred of stereotypes, but it was impossible for any of us to ignore the contrast – a group of grey-haired serious looking doctors (all in suits), and a group of teenage girls with their mums (all in cowboy boots). What do you get when you mix an Oncology Medical Conference and a Taylor Swift Concert? Turns out you get a lot of laughter in a crowded lift. I was asked where I fit in. “Neither” I answered, “and a bit of both”. There is something about ASCO that creates special moments.

Saturday kicked off early; the 8am clinical science symposium addressing the promise of neoadjuvant immunotherapy across solid tumours. Dr Heather Wakelee presented data from KEYNOTE-671, a Phase III trial investigating perioperative pembrolizumab in early-stage NSCLC. This is just one of several trials looking at immunotherapy (IO) in this setting, exploring the benefit of administering IO both pre- and post-surgery. KEYNOTE-671 trials up to 4 cycles of neoadjuvant pembrolizumab (+ chemo), followed by surgery, followed by up to 13 cycles of pembrolizumab monotherapy. Primary endpoints were event-free survival (EFS) and overall survival (OS), and the curve separation of the active vs placebo arm in this interim analysis was clear; EFS at 24 months was 62.4% (in the active arm) vs 40.6% (placebo arm). The hazard ratio at time of analysis was 0.58, with this significant benefit seen across almost all sub-groups analysed. The OS curves began to clearly separate at 2 years; median OS was not yet reached for the active arm at the point of this interim analysis.

Achieving a pathological complete response (pCR) to neoadjuvant therapy means that there is no viable residual tumour detected in the resected specimen. It indicates the neoadjuvant therapy has worked well, and is linked with better long-term outcomes for the patient. In the active arm of this study, 18% of patients achieved pCR. This - as with other neoadjuvant trials before it - is significantly better than the placebo arm, however there is still a gap to the higher pCR rates we associate with the likes of HER2+ve breast cancer.

KEYNOTE-671 clearly supports the use of perioperative IO in early-stage NSCLC, as does the impressive data from the Phase III Neotorch read-out later in the day, showing a statistical benefit of perioperative toripalimab in Stage III NSCLC. As did the positive data from the Phase III AEGEAN trial investigating durvalumab in Stage IIA-III resectable NSCLC back in March. However, both sessions at ASCO today ended with debate over the benefit of a perioperative strategy versus a neoadjuvant only, or adjuvant only approach, and how to identify which patients will benefit from which approach. There is a clearly expressed need for prospective clinical trials comparing the three strategies, rather than the current reliance on cross-trial comparisons which is, as one attendee put it, ‘fraught with danger’. It was poignant that a panel member ended the first half of afternoon’s Lung cancer oral session admitting that mistakes had been made by the Oncology community in trial design in the metastatic setting, and these same mistakes were now being repeated in early-stage. Advances are happening at such pace, with such intent, but there is a need to take a pause, as a group, to determine a homogenous and structured approach to trial design.

On leaving the morning session, I walked the 17,000 miles to the Poster presentation area where my colleague, Ayse Levent, was presenting Ipsos real-world evidence on biomarker testing rates in NSCLC. A doctor from Germany was reviewing Ayse’s poster and we got to talking. He was a lung cancer specialist from a leading academic institute in Munich, so I took the opportunity to ask his thoughts on the clinical significance of neoadjuvant and/or adjuvant IO therapy in NSCLC. He was clearly excited by the imminent availability of nivolumab in the neoadjuvant setting and would definitely use the approach (once approved) when a suitable patient presents to him. His expectation for the next 5 years was that that there will be more clearly defined parameters on which to make the decision of neoadjuvant, adjuvant or both for his early-stage patients; with more data on patient types and the impact of biomarkers. However, he very quickly brought the conversation back to the here and now, and the challenges of today. “Look at this poster. We still have doctors who don’t truly understand why we should conduct biomarker tests, even in metastatic lung cancer”.

Further advances in early-stage NSCLC are coming. However, it seems there is still a need to fully embed the advances of the last 10 years, to ensure they benefit all patients.