SWOG Analyses Shine at ESMO, ASCO Quality Care

Primary results from the S1801 trial in patients with operable stage III-IV melanoma were presented at last year’s ESMO Congress, and were subsequently published in the New England Journal of Medicine. They showed a significant benefit in event-free survival times for patients starting immunotherapy before surgery versus after surgery.

At ESMO 2023 this week, Dr. Sapna Patel, S1801 study chair (and SWOG melanoma committee chair), presented a late-breaking abstract featuring results of exploratory analyses from the trial.

In a central review of surgical specimens from patients on the neoadjuvant arm, just over one half of tissue samples submitted showed a major pathologic response to pre-surgery pembrolizumab – that is, no more than 10 percent residual viable tumor remained in the tumor bed. All specimens were reviewed by the same pathologist, who was blinded to clinical outcomes. 

This significant response in so many patients raises hopes that future neoadjuvant regimens could reduce the extent of surgery needed in these patients – or in some cases eliminate the need entirely.

Among numerous clinical trials of adjuvant therapy in renal cell carcinoma published over the last two decades, only two have reported positive results: the S-TRAC trial of sunitinib and the KEYNOTE-546 trial of pembrolizumab. 

Our S0931 EVEREST came close to being the third. Led by Dr. Christopher Ryan, SWOG executive officer for GI, GU, melanoma, and early therapeutics research, it was the first phase III trial of an adjuvant mTOR inhibitor (everolimus) in these patients. Primary results, presented at ASCO 2022 and published in The Lancet, showed improved recurrence-free survival for patients on the everolimus arm, but results fell just shy of the predefined level for statistical significance.

S0931, however, treated a wide swath of patients, including both clear-cell and non-clear cell histologies, and patients at intermediate-high and very high risk of recurrence. S-TRAC and KEYNOTE-546, by contrast, had enrolled only patients with clear-cell disease who were considered to be at very high risk.

So, an S0931 secondary analysis was performed on a similarly narrow subgroup of patients – those with clear-cell histology who were at very high risk of recurrence. Dr. Primo “Lucky” Lara, SWOG’s deputy group chair and group co-chair-elect, presented results in Madrid this week.

Among patients in this subgroup, those who received adjuvant everolimus had a statistically significant improvement in recurrence-free survival compared to those getting a placebo.

This subgroup analysis could help designers of future trials in this space interpret S0931’s results in the context of the positive S-TRAC and KEYNOTE-564 trials. It should be noted that results of those trials were key in gaining FDA regulatory approval of sunitinib and pembrolizumab as adjuvant therapies in renal cell carcinoma – the only FDA approvals in this setting to date.

The third set of results I want to highlight are findings from a pre-implementation analysis informing the conduct of an ongoing study.

S2108CD is a cluster-randomized study testing whether a remote, educationally enhanced genomic tumor board can help oncology practices that have limited access to local tumor boards. Study co-chair Dr. Jens Rueter just presented the trial at our translational medicine plenary session in Chicago. If you missed it, the recording should soon be posted to the SWOG website.

The study’s other co-chair, Dr. Meghna Trivedi, is lead author on an abstract being presented today at the ASCO Quality Care Symposium, by co-author Dr. Alissa Michel. The abstract assesses the baseline use of genomic tumor testing among physicians at S2108CD rural and community oncology sites, and the physicians’ confidence in using such testing.

Most of those surveyed reported they were moderately or very confident in their abilities to determine when genomic testing is appropriate, to use its results in making clinical decisions, and to explain it to their patients.

But interviews revealed the doctors were somewhat less confident in their abilities to make treatment decisions about genome-informed therapy when there was no clear FDA guidance to rely on. The remote tumor board model being tested in S2108CD is designed to provide critical information to help clinicians with just such decisions.

We learned yesterday that this analysis has been selected as a Journal of Clinical Oncology Featured Abstract, an honor reserved for the most important abstracts “on the topics critical to measuring patient and caregiver experience, provider efficiency, clinical outcomes, and quality and safety in the cancer care field.”

So, congratulations to the S2108CD team! And congratulations to the S1801 and S0931 teams as well! 
 

Reminder: The post group meeting survey is still open (though not for much longer) and there’s still time to claim Continuing Medical Education (CME) credits for sessions you attended at the Chicago meeting.

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Trial of the Week

S1925: Randomized, Phase III Study of Early Intervention with Venetoclax and Obinutuzumab Versus Delayed Therapy with Venetoclax and Obinutuzumab in Newly Diagnosed Asymptomatic High-Risk Patients with Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL): EVOLVE CLL/SLL Study

S1925 is enrolling patients with high-risk chronic lymphocytic leukemia (CLL) or small cell lymphocytic lymphoma (SLL) who have been diagnosed within the previous 12 months but are not yet experiencing symptoms of the disease.

The study asks whether starting these patients on treatment with targeted therapy immediately versus waiting until the onset of symptoms (active surveillance is a standard approach) can extend overall survival. 

It also looks at whether early treatment improves patients’ health-related quality of life. Early treatment may ease the anxiety that often comes with waiting, but it can also bring treatment-related toxicity.

S1925 was activated at the end of 2020 and has accrued 81 patients at 40 sites, with a goal of enrolling 247 patients. The study has been opened at more than 500 sites.

Deborah Stephens, DO, is S1925 study chair, and her home institution, the University of Utah’s Huntsman Cancer Institute, is the accrual leader on the trial, by a wide margin. 

Three other institutions are clustered in a near-tie for second place: University of Rochester, Ohio State University Comprehensive Cancer Center, and Cleveland Clinic. 

Learn more on the SWOG S1925 page or the CTSU S1925 page. A patient-friendly summary of S1925 is also available to use as an aid in presenting the study to patients (a Spanish-language version is posted as well).