Markman’s Take: Vibostolimab in dMMR Endometrial Cancer, Adjuvant Chemo in Cervical Cancer, and More

Maurie Markman, MD

Although strides with systemic therapy were a key aspect of this year’s gynecologic oncology track at the 2024 ASCO Annual Meeting, some of the more notable presentations included those highlighting the adequacy of less intensive treatment interventions, according to Maurie Markman, MD.

“The abstracts from this year’s ASCO gynecologic oncology session really focused on topics that are quite relevant, that go beyond the question of what the next best drug is––although that’s a critical component of what we do in the gynecologic cancer space and medical oncology [as a whole],” Maurie Markman, MD, editor-in-chief of OncologyLive®, said.

The first study looked at what Markman termed a “novel concept.” The study evaluated the activity of the humanized IgG1 anti-TIGIT antibody vibostolimab (MK-7684) coformulated with pembrolizumab (Keytruda) in patients with pretreated mismatch repair–deficient (dMMR) endometrial cancer. Results from cohort B1 (n = 40) of the trial showed that at a median follow-up of 17.2 months (range, 7.7-23.4), the investigator-assessed objective response rate (ORR) was 65% (95% CI, 48%-79%) by RECIST v1.1 criteria.¹ The median progression-free survival (PFS) and overall survival (OS) were 15.0 months (95% CI, 8.1-15.6) and not reached ([NR] 95% CI, 16.1-NR), respectively.

Results from the second study, which pooled data from the National Cancer database, demonstrated no difference in long-term OS outcomes in premenopausal patients with clinical stage I endometrial cancer who received primary hormonal therapy vs primary hysterectomy. The 2-, 5-, and 10-year OS rates for women who received hormonal therapy (n = 1187) were 98.6% (95% CI, 97.7%-99.2%), 96.8% (95% CI, 95.3%-97.8%), and 92.7% (95% CI, 89.8%-94.8%), respectively, vs 99.4% (95% CI, 98.6%-99.7%), 98.5% (95% CI, 97.3%-99.2%), and 96.8% (95% CI, 94.7%-98.1%), respectively, for those who received primary hysterectomy (n = 14,662; HR, 1.84; 95% CI, 1.06-3.21).² However, when evaluated by age, women between the ages of 40 and 49 years experienced a detriment with hormonal therapy (HR, 4.94; 95% CI, 1.89-12.91) vs women under the age of 40 years (HR, 1.00; 95% CI, 0.50-2.00).

The third study collected data from the United States Cancer Statistics database from between 2001 and 2018 and the National Health and Nutrition Examination Survey from 1988 to 2018 and showed a temporal correlation between the increasing incidence of endometrial cancer and obesity measured by average annual percentage changes (AAPC). The results illustrated disproportionate associations in younger women between the ages of 20 and 29 years (cancer: AAPC, 4.48%; P <.0001; obesity: AAPC, 7.36%; P <.05) and women of color (cancer in Black women: AAPC, 1.30%; P <.0001; obesity: AAPC, 3.89%; P <.05).³

Finally, findings from the phase 3 NRG Oncology/RTOG 0724/GOG-0724 trial (NCT00980954) indicated that adjuvant chemotherapy following concurrent chemoradiation (n = 103) did not improve disease-free survival ([DFS]; HR, 1.05; 90% CI, 0.65-1.68; 1-sided long-rank P =.56)) or OS (HR, 0.91; 90% CI, 0.49-1.69; 1-sided long-rank P =.40) vs concurrent chemoradiation alone (n = 109) in high-risk patients with early-stage cervical cancer following radical hysterectomy.4 The 4-year DFS and OS rates in the investigational arm were 76.9% and 89.0%, respectively, vs 76.2% and 87.3%, with chemoradiation alone, respectively.

In this special with OncLive, Markman, who is president of medicine & science at City of Hope Atlanta, Chicago, and Phoenix, discussed the significance of each trial and the conclusions that can be drawn from these research efforts.

Abstract 5502: Vibostolimab Coformulated With Pembrolizumab in Advanced dMMR Endometrial Cancer

Markman: The first [trial] I wanted to briefly mention looked at a novel concept. The drug was vibostolimab, which is a TIGIT inhibitor, which is a checkpoint in our immune system. This drug, which is an investigative agent, was coformulated with pembrolizumab. The idea was to give two checkpoint inhibitors together, and this abstract [reported on this approach in] patients with dMMR endometrial cancer. All these patients had previously been treated and had not received pembrolizumab or any other checkpoint inhibitor. There was a total of 40 patients in the trial, 31 had received 1 prior regimen, and 9 had received 2 or more prior regimens.

The ORR seen in this phase 3 study was 65% and although that by itself is interesting, the median duration of response was greater than 1 year; in fact, 75% of the responses lasted longer than 1 year. These are early-phase [data]. Much more needs to be done, but [these are] very provocative data in a population where we need additional therapy. [So], two checkpoint inhibitors in previously treated patients. What role will this play in the standard of care [SOC] in the previously treated setting, or perhaps in the future, even earlier in the course of the illness?

Abstract 5508: Long-Term Survival With Hormonal Therapy in Premenopausal, Clinical Stage I Endometrial Cancer

The second study I wanted to highlight was a very provocative database study, looking at long-term survival outcomes in women with early-stage endometrial cancer; these were all premenopausal women. The study evaluated over 15,000 patients from the National Cancer database. Investigators looked at [patients with] clinical stage I, grade 1/2 disease who were treated with primary hysterectomy vs primary hormone therapy. The goal here would be to potentially not have to [perform] hysterectomy in a younger age woman, both from the perspective of having children, but also quality-of-life [QOL] issues that might come up. What was very interesting is if one looked at the 5-year OS [rate] in women who underwent this therapeutic strategy, there was no difference in 5-year survival for women under the age of 40 years, but in women aged 40 to 49, there was a statistically significant difference. The hazard ratio was almost 5 for survival detriment in women who received the hormonal strategy as the primary treatment. These were database data, so a lot of details are not known, but this clearly needs to be looked at further. In other words, women aged 40 to 49 years should not undergo primary hormonal therapy, even if they have stage I, grade 1/2 disease, [because they will experience a] detriment in survival. Much more will hopefully follow on that observation.

Abstract 5507: Endometrial Cancer and Obesity Trends in the United States

The next study I want to briefly mention is not new news but notes the extreme relevance of what we know now is an increase in endometrial cancer in the United States and the obesity epidemic. This study looked at 2 databases. One was the United States cancer statistics from 2001 and 2018 looking at the incidence of endometrial cancer. The investigators also looked at a different database, the National Health and Nutrition Examination Survey, from 1988 to 2018, to identify trends of obesity in the United States. If one looks at these two databases together and looks at the increase [in endometrial cancer and obesity] over this period, the link between the two is remarkable and very disturbing. The data are very striking and indicate that we have to figure out what to do about it.

Abstract 5504: Adjuvant Chemotherapy After Chemoradiation in High-Risk, Early-Stage Cervical Cancer Following Radical Hysterectomy

The final paper I want to mention is on the long-term results of an extremely important phase 3 randomized trial that looked at the question of adjuvant chemotherapy following concurrent chemoradiation therapy in patients with high-risk, early-stage cervical cancer following primary hysterectomy. We now know, and we’ve known for a very long period, that the use of chemoradiation improves long-term survival in the high-risk population, and it is SOC. The question is: Is there value in adding adjuvant chemotherapy after chemoradiation is completed?

This trial [sought to answer this question]. It was conducted from 2009 to 2022 and randomly assigned 236 patients to standard chemoradiation or chemoradiation plus carboplatin and paclitaxel. The results definitively showed that there was no benefit from adding carboplatin and paclitaxel. [The addition of adjuvant chemotherapy] adds toxicity [negatively affecting] QOL and does not improve PFS or OS. That doesn’t mean that we don’t have a need for more therapy. Other strategies might be considered, but additional chemotherapy following chemoradiation does not improve outcomes, and there is no reason it should be given.

References

1. Rojas C, Eskens F, Ghiringhelli F, et al. Vibostolimab coformulated with pembrolizumab (vibo/pembro) for previously treated advanced mismatch repair–deficient (dMMR) endometrial cancer: results from cohort B1 of the phase 2 KEYVIBE-005 study. J Clin Oncol. 2024;42(suppl 16):5502. doi:10.1200/JCO.2024.42.16_suppl.5502
2. Long-term survival outcomes for hormonal therapy in premenopausal patients with clinical stage I endometrial cancer. J Clin Oncol. 2024;42(suppl 16):5508. doi:10.1200/JCO.2024.42.16_suppl.5508
3. Endometrial cancer and obesity trends in the United States in the 21st century. J Clin Oncol. 2024;42(suppl 16):5507. doi:10.1200/JCO.2024.42.16_suppl.5507
4. Adjuvant chemotherapy following concurrent chemoradiation (CRT) in patients with high-risk early-stage cervical carcinoma following radical hysterectomy: Results of NRG oncology/RTOG 0724/GOG-0724. J Clin Oncol. 2024;42(suppl 16):5504. doi:10.1200/JCO.2024.42.16_suppl.5504