Eileen M. O’Reilly, MD, is the Winthrop Rockefeller Endowed Chair of Medical Oncology and section head of hepatopancreaticobi at Memorial Sloan Kettering Cancer Center, as well as codirector of medical initiatives at the David M. Rubenstein Center for Pancreatic Cancer Research, in New York.

Eileen M. O’Reilly, MD, discusses the potential of tumor treating fields for the treatment of patients with locally advanced pancreatic cancer.

Dr O’Reilly on the Potential of TTFields in Unresectable, Locally Advanced Pancreatic Cancer

“[PANOVA-3] is an interesting and positive study looking at the addition of tumor treating fields to gemcitabine/nab-paclitaxel in locally advanced, unresectable pancreatic cancer. This trial met its primary end point of overall survival.”

Eileen M. O’Reilly, MD, the Winthrop Rockefeller Endowed Chair of Medical Oncology and section head of hepatopancreaticobi at Memorial Sloan Kettering Cancer Center, as well as codirector of medical initiatives at the David M. Rubenstein Center for Pancreatic Cancer Research, discussed the potential of tumor treating fields (TTFields) in patients with unresectable, locally advanced pancreatic adenocarcinoma.

The randomized, open-label, global, multicenter phase 3 PANOVA-3 trial (NCT03377491) evaluated gemcitabine plus nab-paclitaxel (Abraxane) with or without TTFields for the treatment of patients with newly diagnosed unresectable, locally advanced pancreatic adenocarcinoma. Of note, the primary end point was overall survival (OS), with secondary end points including progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR).

Findings from PANOVA-3 trial showed that the study met its primary end point, O’Reilly began. Notably, the median OS was 16.2 months (95% CI, 15.0-18.0) and 14.2 months (95% CI, 12.8-15.4) in the gemcitabine/nab-paclitaxel plus TTFields (n = 285) vs the gemcitabine/nab-paclitaxel (n = 286) arms, respectively (HR, 0.82; 95% CI, 0.68-0.99; log-rank 

 = .039). Furthermore, the 1-year OS rate was significantly improved with concomitant TTFields compared with gemcitabine/nab-paclitaxel, specifically at 68.1% (95% CI, 62.0%-73.5%) vs 60.2% (95% CI, 54.2%-65.7%) in the respective arms (

The data also demonstrated a reduction in pain for patients who were treated with TTFields, of which pain is a significant aspect of locally advanced pancreatic cancer, O’Reilly noted. The results revealed that pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel compared with the chemotherapy regimen alone. In particular, the median pain-free survival was 15.2 months (95% CI, 10.3-22.8) and 9.1 months (95% CI, 7.4-12.7) in the TTFields plus gemcitabine/nab-paclitaxel compared with gemcitabine/nab-paclitaxel alone, respectively (HR, 0.74; 95% CI, 0.56-0.97; log-rank 

Looking ahead, identifying whether TTFields can be combined with local therapies and immunotherapy could be a potential next step, O’Reilly said. Currently, there are a handful of positive pancreatic cancer trials, with PANOVA-3 as a first in the local advanced setting, she concluded.

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Dr O’Reilly on the Rapidly Evolving Role of Local Therapy in Advanced or Metastatic Pancreatic Cancer

"[There is] a lot more to come [with local therapy], especially as therapies get better in pancreas cancer, and I can see this being an area that's going to be increasingly developed."

Eileen M. O’Reilly, MD, the Winthrop Rockefeller Endowed Chair of Medical Oncology; chair of the Human Research Protection Program and Institutional Review Board; co-director of Medical Initiatives in the David M. Rubenstein Center for Pancreatic Cancer Research; and section head of Hepatopancreaticobiliary Service at Memorial Sloan Kettering Cancer Center, discussed the evolving role of local therapy in the management of metastatic pancreatic cancer, with a focus on patterns of disease progression and the potential for integrating locoregional approaches in select patient populations.

According to O’Reilly, some patients with metastatic pancreatic cancer—particularly those who develop isolated lung metastases—can experience a more indolent disease course, prompting a role for local therapies. However, in more common clinical scenarios, such as patients with liver metastases, the role of local therapy needs further refinement, O’Reilly said. She highlighted the biological distinction between patients with synchronous liver metastases, which present at initial diagnosis, and metachronous metastases, which arise after initial treatment. She noted that although local therapy is generally not recommended in the setting of synchronous liver metastases due to limited supporting evidence, retrospective data suggest a potential role for local interventions, such as ablation or resection, in patients with metachronous disease. However, she cautioned that these data should be interpreted with caution given their non-prospective nature.

Several prospective trials are now investigating the impact of local therapies in patients with metastatic pancreatic cancer, she continued. O’Reilly referenced the phase 2 EXTEND trial (NCT03599765) conducted by The University of Texas MD Anderson Cancer Center, which was a small, prospective, randomized study that evaluated the addition of radiation therapy to metastatic lesions in patients with oligometastatic pancreatic cancer. The study demonstrated a progression-free survival advantage, though no statistically significant improvement in overall survival was observed, she said.

As systemic therapies continue to improve, the consideration of local therapy in select patients with advanced pancreatic cancer may become more relevant, O’Reilly concluded.

Eileen M. O’Reilly, MD, discusses the rapidly evolving role of local therapy in the management of advanced/metastatic pancreatic cancer.

Dr O’Reilly on the Rapidly Evolving Role of Local Therapy in Metastatic Pancreatic Cancer

Eileen M. O'Reilly, MD, gastrointestinal oncologist, Winthrop Rockefeller Endowed Chair of Medical Oncology, co-director, Medical Initiatives, David M. Rubenstein Center for Pancreatic Cancer Research, section head, Hepatopancreaticobiliary & Neuroendocrine Cancers, Memorial Sloan Kettering Cancer Center, discusses survival outcomes from the phase 3 NAPOLI 3 trial (NCT04083235) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC).

At the 2023 ASCO Annual Meeting, O’Reilly and colleagues presented updated data from the phase 3 trial, which demonstrated that treatment with NALIRIFOX—liposomal irinotecan (Onivyde) plus 5-fluorouracil (5-FU), leucovorin, and oxaliplatin—led to a median overall survival (OS) of 11.1 months (95% CI, 10.0-12.1) compared with 9.2 months (95% CI, 8.3-10.6) for nab-paclitaxel (Abraxane) plus gemcitabine (HR, 0.83; 95% CI, 0.70-0.99; 

 = .04). The 12- and 18-month OS rates were 45.6% (95% CI, 40.5%-50.5%) and 26.2% (95% CI, 20.9%-31.7%) for NALIRIFOX, respectively, compared with 39.5% (95% CI, 34.6%-44.4%) and 19.3% (95% CI, 14.8%-24.2%) for nab-paclitaxel/gemcitabine, respectively.

Additionally, NALIRIFOX elicited an objective response rate (ORR) of 41.8% (95% CI, 36.8%-46.9%) vs 36.2% (95% CI, 31.4%-41.2%) for nab-paclitaxel/gemcitabine.

Previous findings presented at the 2023 Gastrointestinal Cancers Symposium

 also showed that first-line treatment with NALIRIFOX produced a clinically meaningful and statistically significant improvement in OS and PFS vs nab-paclitaxel plus gemcitabine. The updated results shared at the 2023 ASCO Annual Meeting built upon these previous outcomes, O'Reilly explains.

When examining these updated results at 12 and 18 months, the outcomes held up in favor of NALIRIFOX compared with nab-paclitaxel plus gemcitabine, O'Reilly expands. Moreover, no matter which time point that an investigator looked at, the outcomes on the NALIRIFOX arm were better relative to nab-paclitaxel plus gemcitabine, supporting the initial results of the study, she says. Although NALIRIFOX produced numerically more responses compared with nab-paclitaxel/gemcitabine, the vast majority of responses in both arms were partial responses, O’Reilly adds.

There was also a longer duration on treatment in the NALIRIFOX arm, O’Reilly continues. As of the July 2022 data cutoff, there were more patients remaining on the study in the NALIRIFOX arm compared with gemcitabine/nab-paclitaxel, O’Reilly concludes.

Eileen M. O'Reilly, MD, discusses survival outcomes from the phase 3 NAPOLI 3 trial in patients with metastatic pancreatic ductal adenocarcinoma.


Dr O'Reilly on Survival Outcomes of the NAPOLI 3 trial in Metastatic PDAC

Eileen O'Reilly, MD, associate director for clinical research at Memorial Sloan Kettering Cancer Center, discusses the role of immunotherapy in patients with pancreatic cancer.

According to O'Reilly, there is compelling science and biology behind using immunotherapy combinations in pancreatic cancer, since single-agent checkpoint inhibitors are insufficient.

In pancreatic cancer, the most promising combination is immunotherapy with a cytotoxic backbone, says O'Reilly. The disease needs to be under control for immunotherapy to work, which is why this combination has become a focus for this patient population.

Eileen M. O'Reilly, MD

Articles

Dr O’Reilly on the Potential of TTFields in Unresectable, Locally Advanced Pancreatic Cancer

Dr O’Reilly on the Rapidly Evolving Role of Local Therapy in Metastatic Pancreatic Cancer

Dr O'Reilly on Survival Outcomes of the NAPOLI 3 trial in Metastatic PDAC

Dr. O'Reilly on Immunotherapy in Pancreatic Cancer