Best Survival Ever in Resectable Pancreatic Cancer



2018 ASCO Annual Meeting, Installment Part 5

BREAKTHROUGH: mFOLFIRINOX After Surgery

likely Nab-P+Gem Before

Everyone:

This posting applies to patients who are resectable at the time of diagnosis, unfortunately not metastatic victims.

News reports call it a “breakthrough.” Oncologists say it “changes clinical practice.”

Abstract LBA4001 was a late release on June 04 at the 2018 ASCO Annual Meeting.

In the report French and Canadian researchers describe the test. At 3 to 12 weeks following surgical resection 493 patients were randomly assigned to receive either Gemcitabine or modified FOLFIRINOX (mFOLFIRINOX) for 6 months – to determine which therapy performed better. Such post-surgery therapy is called adjuvant chemotherapy. And Gemcitabine monotherapy has been a frequent adjuvant choice, because the patient is weakened by surgery.

The patient outcome was dramatic.

1. At a median follow-up of 33.6 months, median overall survival was much longer in the mFOLFIRINOX group (54.4 vs 35.0 months), as was the median disease-free survival (21.6 vs 12.8 months). Of course most of the survival time is due to the surgical resection itself.

2. mFOLFIRINOX also markedly extended the time until metastases appeared (30.4 months for mFOLFIRINOX vs 17.0 months for Gemcitabine).

3. The 3-year disease-free survival was also superior in the mFOLFIRINOX group compared with the Gemcitabine group (39.7% vs 21.4%).

4. The 3-year overall survival was 63.4% vs 48.6% in favor of FOLFIRINOX, and 3-year cancer specific survival was 66.2% vs 51.2%.

5. Grade 3/4 adverse events were more common in the mFOLFIRINOX group than in the gemcitabine group (76% vs 53%), including 12% with grade 4 events in each group, but the side effects were manageable. Commentary on Abstract LBA4001 is available here:



What Chemo Sequence, The Difficult Neoadjuvant Decision. This is fine performance for mFOLFIRINOX. The next question is: What should be the NEOADJUVANT chemotherapy (therapy BEFORE surgery) for initially resectable patients? The Surgery-First vs Neoadjuvant-First debate has determined (to large extent) that newly-arrived resectable patient should begin with neoadjuvant chemotherapy, rather than go directly to surgery (see previous posts on the debate).

Many oncologists typically start with FOLFIRINOX, if the patient is strong. But now the neoadjuvant therapy will likely have to be Nab-Paclitaxel + Gemcitabine (+ Cisplatin for BRCA defect patients).

But, Nab-Paclitaxel + Gemcitabine is not a disadvantage, at least not for metastatic patients, according to research presented in January 2018 at the ASCO GI Symposium. See Installment Part 2 which shows Nab-Paclitaxel + Gemcitabine to be superior to FOLFIRINOX, especially in strong patients. See



Be sure to study the full range of other topics at my website:



PhilipJax

Check for June 4 posting:

Dr. Conroy Discusses Adjuvant mFOLFIRINOX in Pancreatic Cancer

Thierry Conroy, MD | Published: Thursday, Jun 07, 2018 |

Thierry Conroy, MD, medical oncologist, director, Institut de Cancerologie de Lorraine, discusses the results of an adjuvant modified FOLFIRINOX regimen (mFOLFIRINOX) in patients with pancreatic cancer.

When given postoperatively, the 4-drug combination of mFOLFIRINOX improved survival compared with standard gemicatbine. Phase III findings presented at the 2018 ASCO Annual Meeting showed that median overall survival (OS) was nearly 20 months longer with a mFOLFIRINOX than with gemcitabine. Median OS with mFOLFIRINOX was 54.4 versus 35.0 months with gemcitabine, which represents a 36% reduction in the risk of death (HR, 0.64; 95% CI, 0.48-0.86; P = .003).

Following surgical resection, patients were randomized to receive either mFOLFIRINOX or gemcitabine for 6 months. The mFOLFIRINOX regimen was administered intravenously (IV) at day 1, followed by 5-fluorouracil via continuous IV infusion over 46 hours, for 12 two-week cycles. Gemcitabine was administered via IV on days 1, 8, and 15 every 28 days for 6 cycles.

In light of these results, investigators say that mFOLFIRINOX should be the new adjuvant standard of care for patients who are fit enough to undergo chemotherapy following surgical resection. Conroy says that although mFOLFIRINOX was more toxic than gemcitabine, it is still a safe regimen with manageable toxicities.

Thierry Conroy, MD, medical oncologist, director, Institut de Cancerologie de Lorraine, discusses the results of an adjuvant modified FOLFIRINOX regimen (mFOLFIRINOX) in patients with pancreatic cancer.

When given postoperatively, the 4-drug combination of mFOLFIRINOX improved survival compared with standard gemicatbine. Phase III findings presented at the 2018 ASCO Annual Meeting showed that median overall survival (OS) was nearly 20 months longer with a mFOLFIRINOX than with gemcitabine. Median OS with mFOLFIRINOX was 54.4 versus 35.0 months with gemcitabine, which represents a 36% reduction in the risk of death (HR, 0.64; 95% CI, 0.48-0.86; P = .003).

Following surgical resection, patients were randomized to receive either mFOLFIRINOX or gemcitabine for 6 months. The mFOLFIRINOX regimen was administered intravenously (IV) at day 1, followed by 5-fluorouracil via continuous IV infusion over 46 hours, for 12 two-week cycles. Gemcitabine was administered via IV on days 1, 8, and 15 every 28 days for 6 cycles.

In light of these results, investigators say that mFOLFIRINOX should be the new adjuvant standard of care for patients who are fit enough to undergo chemotherapy following surgical resection. Conroy says that although mFOLFIRINOX was more toxic than gemcitabine, it is still a safe regimen with manageable toxicities.

SEE ALL VIDEOS FROM: Thierry Conroy, MD

2018 ASCO: Adjuvant mFOLFIRINOX vs Gemcitabine in Resected Pancreatic Cancer

By The ASCO Post | Posted: 6/4/2018 11:07:23 AM Last Updated: 6/4/2018 11:07:23 AM |

Key Points

• At a median follow-up of 33.6 months, the median disease-free survival was much longer in the mFOLFIRINOX group than in the gemcitabine group (21.6 vs 12.8 months), as was the median overall survival (54.4 vs 35.0 months).

• mFOLFIRINOX also markedly extended the time until metastases appeared (median = 30.4 months vs 17.0 months with gemcitabine).

• Overall, more patients experienced severe side effects (mainly hematologic) in the mFOLFIRINOX group than in the gemcitabine group (76% vs 53%), but the side effects were manageable.

In a randomized phase III trial, patients with surgically removed pancreatic cancer who received mFOLFIRINOX (a modified regimen containing oxaliplatin, leucovorin, irinotecan, and fluorouracil) lived a median of 20 months longer and were cancer-free 9 months longer than those who received the current standard of care, gemcitabine. The study was featured in a press briefing today and presented by Conroy et al at the 2018 ASCO Annual Meeting (Abstract LBA4001).

“For the first time, our trial shows a large benefit from adjuvant FOLFIRINOX chemotherapy over standard chemotherapy with gemcitabine, showing we can help patients with pancreatic cancer live much longer,” said lead study author Thierry Conroy, MD, a medical oncologist and Director of the Institut de Cancerologie de Lorraine in Nancy, one of the UNICANCER Comprehensive Cancer Centers in France. “In addition, we were encouraged to see that the results were better than expected when we planned this trial.”

After pancreatic cancer surgery, adjuvant chemotherapy with gemcitabine can substantially prolong survival compared to surgery alone, as well as increase the number of patients who will probably not relapse from pancreatic cancer (at 5 years, about 21% with gemcitabine vs 10% with surgery alone). Gemcitabine has been the standard adjuvant therapy for the past 10 years.

About the Study

The PRODIGE 24/CCTG PA.6 trial enrolled patients with nonmetastatic pancreatic ductal adenocarcinoma who had surgery that removed all or nearly all of the tumor (meaning no cancer cells visible to the surgeon after surgery, but microscopic tumoral cells may have remained).

At 3 to 12 weeks after surgery, 493 patients were randomly assigned in France and Canada to receive either gemcitabine or mFOLFIRINOX for 6 months. A regimen very similar to mFOLFIRINOX is already used as an initial treatment for metastatic pancreatic cancer, and this study shows FOLFIRINOX can also benefit patients with earlier-stage disease.

Key Findings

At a median follow-up of 33.6 months, the median disease-free survival was much longer in the mFOLFIRINOX group than in the gemcitabine group (21.6 vs 12.8 months), as was the median overall survival (54.4 vs 35.0 months). The benefit of the mFOLFIRINOX was observed in all patient subgroups. mFOLFIRINOX also markedly extended the time until metastases appeared (median = 30.4 months vs 17.0 months with gemcitabine).

Overall, more patients experienced severe side effects (mainly hematologic) in the mFOLFIRINOX group than in the gemcitabine group (76% vs 53%), but the side effects were manageable, according to the authors. One treatment-related death occurred in the gemcitabine group, and none occurred in the mFOLFIRINOX group.

The types of side effects also differed between the two groups. The most common side effects of gemcitabine were headache, fever, flu-like symptoms, swelling, and leukopenia. Patients who received mFOLFIRINOX had more diarrhea, nausea, vomiting, and fatigue. There was no difference in the risk of febrile neutropenia between the two groups.

A past history of ischemic heart disease represents a risk with either regimen, but particularly mFOLFIRINOX. Patients should be assessed for underlying heart disease before starting this adjuvant treatment, a precaution that is routine for many people with cancer receiving surgery and chemotherapy.

Next Steps

The next step will be to explore the timing of chemotherapy. Patients may benefit from neoadjuvant chemotherapy to destroy undetectable micrometastases and increase the chance that the tumor can be completely removed through surgery. Dr. Conroy noted that mFOLFIRINOX appears to be a good candidate for neoadjuvant chemotherapy. Another option is to give perioperative chemotherapy. Ongoing clinical trials are already testing both of these approaches.

This study, sponsored by UNICANCER, Paris, received funding from the Institut National du Cancer in France, French National League Against Cancer, Canadian Cancer Society, and “7 Days in May,” a charity cycling event in Canada.

Best Survival Ever in Resectable Pancreatic Cancer

Roxanne Nelson, BSN, RN | June 04, 2018

CHICAGO — A new standard of care has emerged for nonmetastatic pancreatic ductal adenocarcinoma (PDAC) in patients who have undergone surgical resection and have a good performance status.

In this patient group, the survival achieved with a modified FOLFIRINOX (mFOLFIRINOX) regimen (composed of oxaliplatin, leucovorin, irinotecan, and 5-fluorouracil) achieved the best survival ever seen with any adjuvant treatment, say researchers presenting new results from a phase 3 study.  

The median overall survival was 54.5 months with mFOLFIRINOX, compared with 35 months with gemcitabine; median disease-free survival was 21.6 months vs 12.8 months, respectively.

"For the first time, our trial shows a large benefit from adjuvant FOLFIRINOX chemotherapy over standard chemotherapy with gemcitabine," said lead study author Thierry Conroy, MD, a medical oncologist and director of the Institut de Cancerologie de Lorraine in Nancy, one of the UNICANCER comprehensive cancer centers in France.

On the basis of these findings, "mFOLFIRINOX should now be considered a new standard of care after pancreatic cancer resection in patients with good performance status," said Conroy. "The median survival with FOLFIRINOX is the best ever achieved with any adjuvant treatment, and there was a 15% increase in survival at 3 years."

The new data were presented here at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting.

Noting that the results show a median overall survival of 4.5 years in pancreatic cancer, Richard Schilsky, MD, chief medical officer of ASCO, commented to Medscape Medical News:  "We are just not used to talking about those sorts of numbers, so I consider this to be a big step forward in the management of patients with resectable cancer."

"What we are seeing is an almost 2-year difference in survival, and that is pretty amazing," given the general dismal prognosis of pancreatic cancer, commented  Daniel Labow MD, system chief of surgical oncology at Mount Sinai and site chair of the Department of Surgery at Mount Sinai St. Luke's and Mount Sinai West, New York City.

 "This combination has already been proven to be more effective in the metastatic setting, and now we're using it in the adjuvant setting, so it's not surprising that we saw good results," he told Medscape Medical News. "Of course, results don't always translate from one setting to another, but in this case, we are seeing that."

He predicts that it will change the standard of care for patients with resectable pancreatic cancer, but he pointed out that only about 20% of patients with pancreatic cancer ever make it to surgery. "So we are already taking patients who have a more favorable prognosis, and giving them a new and effective regimen, and what this is confirming — and in a positive way — that long-term survival is possible," he said. "It's all very encouraging, and the next step is if we can get more people to surgery by using FOLFIRINOX or another regimen."

"This trial is basically confirmatory that the four-drug regimen and surgery can result in long-term survival, and this should be the standard of care in patients who can tolerate it," Epstein added.

Superior for All Endpoints

Adjuvant chemotherapy is used to reduce the risk for recurrence in pancreatic cancer, and 6 months of gemcitabine and/or fluoropyrimidine has been the standard treatment in this setting since 2008, explained Conroy. "However, 71% to 76% of patients still relapse within 2 years despite these treatments, and there is an obvious need for a more efficient regimen to cure patients."

FOLFIRINOX is more effective than gemcitabine in the metastatic setting, Conroy noted. "But as it could be too toxic for the adjuvant setting, a modified regimen was developed without the bolus of fluorouracil."

The modified regimen is associated with less hematologic toxicities and diarrhea, but efficacy is not affected, he said.

In their multicenter study, Conroy and colleagues assessed the benefit of mFOLFIRINOX in the adjuvant setting in a cohort of 493 patients who were enrolled from 77 centers in France and Canada. All patients had undergone resection for nonmetastatic disease and were randomly assigned 21 to 84 days after surgery to receive gemcitabine (given in 28-day cycles on days 1, 8, and 15 for 6 cycles) or mFOLFIRINOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m² D1, and 5-fluoroucil 2.4 g/m² over 46 hours) every 14 days for 12 cycles.

At a median follow-up of 33.6 months, the median disease-free and overall survival durations were much longer in the mFOLFIRINOX group than in the gemcitabine group, as was metastasis-free survival  (median, 30.4 months vs 17.0 months with gemcitabine; hazard ratio, 0.59). 

The 3-year disease-free survival was also superior in the mFOLFIRINOX group compared with the gemcitabine group (39.7% vs 21.4%).

Similarly, 3-year overall survival was 63.4% vs 48.6% in favor of the combination regimen, and 3-year cancer specific survival was 66.2% vs 51.2%.

"The superiority of FOLFIRINOX was observed in all predefined patient subgroups," said Conroy.

Grade 3/4 adverse events were more common in the mFOLFIRINOX group than in the gemcitabine group (76% vs 53%), including 12% with grade 4 events in each group. There was one treatment-related death in the gemcitabine group, and none in the mFOLFIRINOX group. 

Conroy explained that the next step will be to explore the timing of chemotherapy and that mFOLFIRINOX appears to be a good candidate for neoadjuvant chemotherapy. Another option is to give it as perioperative chemotherapy; ongoing clinical trials are already investigating both of these approaches.

Practice-Changing

ASCO expert Andrew Epstein, MD, agreed with the authors that this does represent a new standard of care in this setting. "There was a significant improvement in survival for a notoriously aggressive disease," he said, and he emphasized that it is important that this chemotherapy regimen is given to patients with a good performance status.

"It would be tempting to give this to anyone after surgery, but it is a relatively challenging regimen and we want to make sure we recommend it to patients who can withstand the rigorousness of this treatment," said Epstein, who is an oncologist at Memorial Sloan Kettering Cancer Center in New York City. "This is one that I would recommend to my patients."

This study, sponsored by UNICANCER, Paris, France, received funding from the Institut National du Cancer in France, French League Against Cancer, Canadian Cancer Society, and "7 Days in May," a charity cycling event in Canada. Conroy reports travel, accommodations, and expenses from Roche; several coauthors report relationships with industry. Epstein disclosed a relationship with UptoDate. Labow has disclosed no relevant financial relationships.  

American Society of Clinical Oncology (ASCO) 2018 Annual Meeting. Presented June 4, 2018. Abstract LBA4001

Major pancreatic cancer breakthrough

Clinical trial results show pancreatic cancer patients nearly twice as likely to survive with new treatment.

By Pranjal Mehar June 4, 2018

Queen's/CCTG researcher Jim Biagi discusses study results with clinical trial participant Kathleen Kennedy.

The pancreatic tumor is regularly exceptionally aggressive, with just around eight percent individuals surviving beyond five years after treatment, even after surgery and the standard chemotherapy treatment. The distressing part of pancreatic cancer is that only a small proportion of patients are candidates for surgery and, even if surgery is successful, most will die of recurrent disease.

A new study by the Queen’s University suggests that increased survival rates for pancreatic cancer patients who received a four-drug chemotherapy combination known as mFOLFIRINOX after surgery. This is life-changing for these patients and should impact how we treat pancreatic cancer around the world.

Scientists involved 493 patients with pancreatic cancer for the surgery. On average, patients who received mFOLFIRINOX lived almost 20 months longer and were cancer-free nine months longer than those who received the standard treatment.

The outcomes recommend the new treatment regimen ought to wind up standard practice around the world. There are additionally some subsequent stages to investigate, incorporating trying different things with the planning of chemotherapy.

Kathleen Kennedy, a Kingston-area resident said, “A few months after my cancer diagnosis, I had surgery and then elected to try this experimental treatment. I knew that there could be risks, but I also knew that it would be helpful – if not immediately to me, then for other pancreatic cancer patients in the future. Now, three disease-free years later, I feel so blessed that this treatment has afforded me more time with my husband, children, and grandchildren.”

Judy Bray, Vice-President of Research at the Canadian Cancer Society said, “Since 1980, more than 80,000 people have received excellent care at over 800 hospitals and cancer centers across the country in clinical trials that we funded. We’re obviously thrilled when discoveries from these trials improve survival and change the way cancer is treated worldwide. We are committed to helping Canadians through the entire cancer journey by investing in research on prevention, detection, diagnosis, treatment and the quality of life of those affected by cancer.”

The study’s co-lead is Thierry Conroy, medical oncologist and director of the Institut de Cancérologie de Lorraine in Nancy – one of the UNICANCER hospital network’s comprehensive cancer centers in France. Funding for the trial was provided by the Institut National du Cancer in France, the French national Ligue against cancer, cycling charity group 7 Days in May and the Canadian Cancer Society.

The PA.6 results were presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

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