ESMO Round-Up: Ritu Salani, MD, Shares Key Insights Ranging From PARP Inhibitors to Immunotherapy in the Advanced Gynecologic Cancer Space

At the 2022 European Society for Medical Oncology (ESMO) Congress, a plethora of clinical data read out within the gynecologic cancer space. In particular, Ritu Salani, MD, cited updates in the PARP inhibitor space for patients with ovarian cancer and findings about immunotherapeutics for endometrial and cervical cancer.

“PARP inhibitors in the frontline setting, particularly HRD [homologous recombination deficiency] and BRCA-mutant disease, is really critical and is making a survival impact. It really should be the standard of care,” Salani, director of gynecologic oncology at the University of California, Los Angeles, said in an interview with CancerNetwork®. “From an immunotherapy standpoint, we’re seeing lenvatinib [Lenvima] and pembrolizumab [Keytruda] in that mismatch repair–proficient [pMMR] population really show survival and quality of life benefits, and should be considered as a second-line option. For cervical cancer, we’re exploring the role of immunotherapies or immunotherapy combinations, particularly with a PD-1 inhibitor and CTLA inhibitor.”

Long-Term Findings With PARP Maintenance in Advanced Ovarian Cancer

One area of excitement at this year’s meeting was maintenance PARP inhibitors for patients with advanced ovarian cancer, according to Salani. In particular, she shined a spotlight on the long-term findings of the phase 3 SOLO-1 trial (NCT01844986) assessing olaparib (Lynparza) maintenance in patients with BRCA-mutated advanced ovarian cancer and the final results of the phase 3 PAOLA-1 trial (NCT02477644) examining maintenance olaparib and bevacizumab (Avastin) in newly diagnosed advanced ovarian cancer.^1,2

“The most exciting thing from [ESMO regarding PARP] inhibitors was the long-term data we’re starting to see in the frontline maintenance [setting], both in SOLO-1 and PAOLA-1,” Salani said. “[These studies] were exciting and show continued benefit in patients who received PARP inhibitors. In PAOLA-1, that [benefit] was shown in both the BRCA-mutant and the HRD population reaffirming the earlier data that we had seen.”

Long-term data from the SOLO-1 trial indicated that patients who were treated with olaparib (n = 260) had 60- and 84-month overall survival (OS) rates of 73.1% and 67.0% compared with 63.4% and 46.5% in the placebo arm (n = 131), respectively. Moreover, the media OS was not reached in the olaparib arm vs 75.2 months in the placebo arm (HR, 0.55; 95% CI, 0.40-0.76; P = .0004).

In the PAOLA-1 trial, patients treated with the olaparib/bevacizumab combination (n = 537) experienced a 5-year OS rate of 47.3% vs 41.5% in the placebo arm (n = 269). Moreover, the median OS was 56.5 months compared with 51.6 months in each respective arm (HR, 0.92; 95% CI, 0.76-1.12; P = .4118). In the HRD-positive subgroup, the 5-year OS rate was 65.5% vs 48.4% in each arm, respectively. The median OS was 75.2 months in the olaparib arm compared with 48.4 months (HR, 0.62; 95% CI, 0.45-0.85). In the subgroup analysis, investigators reported that treatment with olaparib/bevacizumab and placebo/bevacizumab yielded 5-year OS rates of 73.2% vs 53.8% in BRCA-mutant patients, 54.7% vs 44.2% in the HRD-positive group excluding those with a BRCA mutation, and 32.3% vs 25.7% in the HRD-negative group.

Latest Innovations in Immunotherapy for Gynecologic Malignancies

Salani touched on some exciting immunotherapy data that read out at the congress, including an updated efficacy analysis of the phase 3 KEYNOTE-775 trial (NCT03517449) assessing lenvatinib and pembrolizumab as treatment for patients with advanced endometrial cancer andof the phase 1/2 CheckMate 358 study (NCT02488759) examining nivolumab (Opdivo) with or without ipilimumab (Yervoy) in a population of patients with recurrent/metastatic cervical cancer.^3,4

“We’re seeing more long-term, mature data,” she explained. “This is interesting because over the last several years, we’ve seen new data and it’s nice to see the long-term activity of these agents. Although there wasn’t anything strikingly new in the immunotherapy realm, we do continue to [see] sustained benefit in these areas and it’s really exciting. Many of us, if not most of us, have already adopted immunotherapy. This once again reaffirms our choice and gives us more confidence in treating patients with these therapies.”

Updated findings from the KEYNOTE-775 study highlighted a continued OS benefit among patients with pMMR-positive endometrial cancer who were treated with the combination vs physician’s choice (HR, 0.64; 95% CI, 0.54-0.76). Moreover, patients in the pMMR population maintained a promising overall response rate of 32.4%, including a complete response rate of 5.8%, in the combination arm vs 15.1% and 2.6% with control therapy, respectively.

In the CheckMate 358 study, patients were treated with nivolumab at 240 mg; 3 mg of nivolumab and 1 mg/kg of ipilimumab; or 1 mg of nivolumab plus 3 mg of ipilimumab in the expansion arm. The median OS between the 3 cohorts was 21.6 months, 15.2 months, and 20.9 months, respectively. Moreover, the 12- and 24-month OS rates were 73% and 43% in the nivolumab arm, 54% and 37% in the combination arm, and 69% and 48% in the expansion cohort, respectively.

References

1. DiSilvestro P, Banerjee S, Colombo N, Scambia G, et al. Overall survival with maintenance olaparib at a 7-Year follow-Up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: the SOLO1/GOG 3004 trial. Ann Oncol. 2022;33(suppl 7):S235-S282. doi:10.1016/annonc/annonc1054
2. Ray-Coquard IL, Leary A, Pignata S, et al. Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC). Ann Oncol. 2022;33(suppl 7):S808-S869. doi:10.1016/annonc/annonc1089
3. Makker V, Colombo N, Casado Herraez A, et al. Updated efficacy and safety of lenvatinib plus pembrolizumab versus treatment of physician’s choice in patients with advanced endometrial cancer: Study 309/KEYNOTE-775. Ann Oncol. 2022;3(suppl 7):525MO. doi:10.1016/annonc/annonc1054
4. Oaknin A, Moore KN, Meyer T, et al. Safety and efficacy of nivolumab (NIVO) ± ipilimumab (IPI) in patients (pts) with recurrent/metastatic cervical cancer (R/M Cx Ca) in checkmate 358. Ann Oncol. 2022;33(suppl 7):S235-S282. doi:10.1016/annonc/annonc1054