Reflections from the Targeted Therapies of Lung Cancer Conference

By Katie Hulan

In February, I had the opportunity to attend the 2026 Targeted Therapies of Lung Cancer Meeting. The conference brought together clinicians and researchers to discuss the latest developments in targeted approaches for lung cancer. It was a space where molecular pathways, Kaplan–Meier curves, and toxicity tables were discussed alongside healthy (and fun) debates and panels. 

A Meeting Where Science Meets Real Life

Across multiple sessions, experts walked through trial and real world data, along with patient cases to explore questions like: How do co‑mutations shape prognosis? When should we be thinking about intratumoural therapies or novel combinations? What do we do when targeted therapies stop working? Each overarching topic was dissected by multiple clinicians or researchers and then opened up to debate, ending with panel discussions that invited questions from the audience and highlighted areas of uncertainty and ongoing research.

These panels weren’t necessarily about finding a single “right” answer. Instead, they modeled how multidisciplinary teams weigh evidence, patient values, and practical constraints in real time. For those of us living with or advocating for ALK‑positive lung cancer, it was reassuring to see such a strong emphasis on nuance: not just “Does this drug work?” but “For whom, for how long, and at what cost to quality of life?”

ALK‑Positive Disease: CROWN Trial, Resistance, and Targeted Protein Degradation

From the CROWN trial, the updated 5‑year results show that first‑line lorlatinib continues to deliver remarkable outcomes, with median progression‑free survival still not reached and a high proportion of patients remaining progression‑free at 5 years. At the same time, there is a subset—roughly around one in five patients—who progress relatively early despite starting on lorlatinib. A key area of active research is understanding this “early progression” group using circulating tumour DNA (ctDNA) and detailed analysis of ALK fusion partners, variants and resistance mechanisms, with the goal of predicting who may need alternative strategies sooner.

Targeted Protein Degradation

Looking forward, one of the most exciting ideas discussed for ALK‑positive disease is targeted protein degradation. How it works: instead of simply blocking ALK kinase activity, these new protein degraders are designed to tag ALK for destruction. by the cell’s own protein‑disposal machinery. Pre‑clinical (before a clinical trial has started) work has identified ALK degraders that show strong activity against some of the most challenging lorlatinib‑resistant compound mutations, and in mouse models they can provide deeper and more durable tumour control than lorlatinib in certain resistance settings. Learn more here.

The long‑term hope is that next‑generation ALK degraders will combine the kind of brain penetration that lorlatinib is known for with improved ability to prevent or overcome resistance, especially if you have been on a few other TKIs. For now, this remains an emerging approach, but it represents a promising avenue for patients in the future who have already exhausted current targeted options.

The Power of Co‑Mutations and Precision

One major theme throughout the meeting was the importance of looking beyond a single driver mutation. Presenters shared data on how common co‑mutations—like TP53, STK11, and others—can influence tumour biology, shape prognosis, and impact how long patients stay on targeted therapies before needing to switch. Seeing these patterns mapped out visually reinforced something many patients already feel: ALK‑positive cancers do not all behave exactly the same, and precision medicine must account for that complexity.

For people living with ALK‑positive non‑small cell lung cancer, researchers are learning that the ALK change is often only part of the story. Tumours can carry additional genomic changes—called co‑mutations—that influence how aggressive the cancer is and how long targeted drugs keep it under control. One co-mutation drawing particular attention is TP53, a kind of “quality‑control” gene that helps repair damaged DNA. When TP53 is also mutated in an ALK‑positive tumour, studies suggest some patients may stay on their first ALK pill for a shorter time. This does not mean ALK therapies stop working altogether, or that everyone with a TP53 mutation will do poorly; rather, it highlights how important comprehensive molecular testing has become. By understanding both the ALK fusion (including its subtype) and co‑mutations like TP53, doctors can better tailor treatment choices, and identify patients who might benefit from clinical trials or more intensive monitoring. 

“Don’t Underplay Toxicity”: Dr. Ross Camidge’s Message

The emotional heart of the conference came from Dr. Ross Camidge, who brought a deeply human lens to a very data‑heavy meeting. He reminded everyone in the room that life does not pause with a lung cancer diagnosis—families, careers, relationships, and everyday responsibilities all continue, even as patients juggle scans, side effects, and uncertainty.

Dr. Camidge spoke about “scanxiety,” the familiar dread many patients feel before imaging results, and how this anxiety can shape every aspect of life between appointments. He urged clinicians not to minimize the burden of side effects or the emotional weight of waiting. His message was clear and direct: “Don’t underplay toxicity.” When toxicity is acknowledged and proactively managed, patients can better plan their lives—work, caregiving, travel, and simple day‑to‑day joys—around treatment rather than feeling trapped by it.

The room was visibly moved. Hearing a respected oncologist speak so candidly about the emotional reality of treatment brought people to tears and then to their feet. For ALK Positive Canada members, this kind of advocacy from within the medical community matters. It validates what patients and caregivers have been saying for years: survival is not the only endpoint; how we live during and after treatment matters just as much.

Looking for “Zero‑Benefit” Groups

Another critical point Dr. Camidge emphasized was the need to identify “zero‑benefit” groups—patients who derive little to no advantage from specific therapies. Rather than viewing this as pessimistic, he framed it as a path to better care. If eventually clinicians can recognize who is unlikely to benefit from a given drug or strategy, they can spare those patients unnecessary toxicity, financial burden, and lost time.

For the ALK community, where we now have multiple generations of TKIs and new agents under investigation, this is particularly relevant. Precision medicine isn’t just about finding what works; it’s also about clearly understanding what doesn’t, so people can move on to more promising options sooner. This mindset aligns with what many in our community advocate for: more biomarker‑driven decision‑making and honest conversations about risk, benefit, and uncertainty.

We Can All Help

These meetings are where current patient outcomes and needs are reviewed, future standards of care are discussed and where new drugs showcase their promise based on trials. Seeing clinicians include patient‑reported outcomes and mention the importance of quality‑of‑life metrics, and lived experience in their talks signals real progress.

It also underscores the importance of us all discussing with our health care teams, what it actually feels like to go through treatment—how side effects affect daily life and your goals, and what success for you looks like in life. When that is respected and integrated, everyone benefits: patients, clinicians, and the science itself.