Camizestrant-Related Photopsia Mostly Mild, Nondisabling in Patients With Advanced Breast Cancer: Adam Brufsky, MD, PhD

Results from the phase 3 SERENA-6 trial (NCT04964934), presented earlier this year at the American Society of Clinical Oncology Annual Meeting, showed that switching to camizestrant (AstraZeneca) when an ESR1 mutation is detected during first-line therapy can help slow cancer growth in patients with hormone receptor (HR)–positive, HER2-negative advanced breast cancer.

As a follow-up, investigators explored the impact of photopsia on patients. This effect of seeing flashes, sparks, or streaks of light was the most commonly reported nonhematological adverse event. Their findings are detailed in a poster titled “Visual Functioning and Characterization of Visual Effects From SERENA-6, a Phase 3 Study of Switch to Camizestrant (CAMI) From Aromatose Inhibitor (AI) While Continuing CDK4/6 Inhibitor (CDK4/6i) at Emergence of ESR1 Mutations (ESR1m) During First-Line Therapy for Patients With HR+/HER2- Advanced Breast Cancer (ABC)," to be presented at the San Antonio Breast Cancer Symposium this Friday by Adam Brufsky, MD, PhD, professor of medicine at the University of Pittsburgh School of Medicine.

Ahead of his presentation, Brufsky discussed the poster’s findings in an interview with The American Journal of Managed Care^®.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

For context, could you summarize the SERENA-6 trial findings, particularly the impact of switching to CAMI from AI while continuing a CDK4/6 inhibitor?

SERENA-6 was a very interesting trial. What happened is that patients who are on a CDK4/6 and an aromatase inhibitor [AI] were tested for the emergence of an ESR1 mutation, generally by Guardant360. If an ESR1 mutation became apparent, then they had a CT scan of the chest, abdomen, and pelvis to see if they had any disease.

If they had no evidence of disease but an emergent ESR1 mutation, they were randomized to continue the AI and CDK4/6 or be switched to camizestrant [CAMI], which is a novel SERD [selective estrogen receptor degrader], and the CDK4/6 inhibitor.

What happened in that trial is that the progression-free survival [PFS] in the camizestrant arm of that study was about probably 300 patients, a little over 300 patients, randomized. In the camizestrant arm of the trial, there was a PFS of about 16 months vs about 9 months for the continued aromatase inhibitor [arm]. Even the second PFS, which was called PFS 2, after they progressed, either on CAMI or the AI, also was better. The most interesting thing over the trial was that the quality of life of the patients who remained on AI and CDK really substantially decreased, whereas it was maintained on camizestrant.

I think this is really the first evidence that using molecular progression, or molecular changes, to change therapy in metastatic breast cancer is a viable strategy. Again, based on the FDA approval of camizestrant, it could potentially be a practice-changing trial.

As you know, photopsia was the most commonly reported nonhematological adverse event. With this in mind, what was the objective of this analysis?

Again, the most common side effect that's, in a way, unique to camizestrant—it's seen a little bit in some of the other SERDs—is photopsia, which is kind of a feeling of bright flashing lights at the edges of your vision. We did extensive quality-of-life testing in SERENA-6, and we're presenting in a poster this year in San Antonio the results of the visual quality of life testing.

I think it's important to know, because I think clinicians who are going to use camizestrant in clinical practice really want to know, are these disabling side effects? Are they something that needs to be brought into the equation when you're thinking about giving someone camizestrant vs another oral SERD or an aromatase inhibitor?

Can you summarize the key findings?

About 20% of the women did have some photopsia. It was mostly grade 1. It really was not disabling at all. We actually did various scope scales and asked the women directly, is this disabling in your life? For the vast majority of people, it was not. It was reversible in just about everybody. It was consistent with some of the phase 2 trials of camizestrant done in the past. There's nothing really new.

The bottom line here is that the photopsia, while a little bit more frequent than [in] the control arm—interestingly enough, there was photopsia in the control arm—by simple visual subscales, by visual parts of patient-related outcome scales, really, by just about every way you could analyze it, the vast majority of these events, which were not incredibly frequent, were grade 1 and nondisabling. That would give everybody comfort at the end of the day, if we're going to use camizestrant, that the photopsia and visual side effects in the real world are not going to be substantial.