One of the top presentations at the top cancer meeting this year has negative results — but this abstract is “very important,” says Lori J. Pierce, MD, president of the American Society of Clinical Oncology (ASCO).

The study, known as OUTBACK, will be presented during a plenary session at the ASCO Annual Meeting 2021, but some details were released at a premeeting press briefing.

The results show that adjuvant chemotherapy added to standard chemoradiation therapy did not improve survival outcomes for women with locally advanced cervical cancer.

It was also associated with higher rates of serious adverse events.

“The last thing we want to do is give a therapy that doesn’t improve outcomes but causes a poorer quality of life to a patient because of increased side effects,” Pierce commented.

“That’s why I think this abstract is very important, and I think it underscores the importance of clinical trials.” 

Pierce told Medscape Medical News that “just because a clinical trial is negative doesn’t mean we don’t talk about it.”

In fact, this trial is practice changing because it will stop clinicians from giving adjuvant therapy now that these data are available. “It also tells us that we need to think of other approaches for clinical trials for patients who progress after they receive their radiation and chemotherapy,” she said. “It tells us to stop doing this, start thinking of other trials we need to run, but absolutely don’t give these patients the adjuvant chemotherapy as was given in the study.”

Practice-Changing Results

Cervical cancer remains a common cause of cancer-related death among women globally, and a significant percentage of women still relapse and die from distant metastatic disease despite treatment.

“Some prior influential trials suggested that giving more chemotherapy after radiation might help and changed practice in some centers,” commented lead trialist Linda R. Mileshkin, MD, a medical oncologist at Peter McCallum Cancer Centre in Melbourne, Australia.

“However the international community felt that there were some flaws in these trials and felt it was important to perform a confirmatory trial,” she explained.

Hence, they conducted the OUTBACK study, an international randomized phase 3 trial of the Gynecologic Cancer InterGroup (GCIG). The cohort included 919 women with locally advanced cervical cancer (FIGO 2008 stage IB1 & node positive, IB2, II, IIIB, or IVA) considered suitable for primary treatment with chemoradiation with curative intent.

Participants were randomized to receive either standard cisplatin-based chemoradiation (control) or standard cisplatin-based chemoradiation followed by adjuvant chemotherapy of 4 cycles of carboplatin and paclitaxel.

Overall survival at 5 years, the primary endpoint, was very similar in the two treatment arms: 72% with adjuvant chemotherapy vs 71% without (hazard ratio [HR], 0.91; P = .91).

The secondary endpoint of progression-free survival at 5 years was also similar for women who received adjuvant therapy versus controls (63% vs 61%; difference 2%; HR, 0.87; P = .61).

There was also no evidence of benefit in subsets of women with high-risk disease, Mileshkin noted.

Typical side effects were significantly increased in the adjuvant chemotherapy arm: grade 3-5 events occurred in 81% of patients in the adjuvant therapy group versus 62% of controls. Quality of life was worse in patients in the adjuvant therapy group, and for the following 3-6 months, but similar between groups at 12 months.

“Adjuvant chemotherapy given after standard cisplatin-chemoradiation in women with locally advanced cervical cancer did not improve overall or progression-free survival,” the authors concluded.

“The standard treatment should continue to be pelvic chemoradiation with concurrent weekly cisplatin,” they added.

“Further research should focus on adjuvant therapies that may be more tolerable and effective when given after standard therapy,” Mileshkin commented.

An expert approached for comment speculated that future “improvements in outcomes for our patients will come from targeted or immunotherapy, not more chemotherapy.”

Richard T. Penson, MD, clinical director of medical gynecologic oncology, at Mass General Cancer Center, Boston, also noted that the advent of chemoradiation for locally advanced cervical cancer triggered an National Cancer Institute alert in 1999, with a 10% improvement in overall survival over radiation alone that was reported in five randomized clinical trials.

“Ten years later, in 2009, the addition of gemcitabine to weekly cisplatin and with 2 adjuvant cycles suggested improved outcomes but with unacceptable toxicity,” Penson said. “It has taken more than a decade since then, and the altruism of nearly a thousand women, to answer the question of adjuvant chemotherapy with the definitive OUTBACK trial in which 4 cycles of adjuvant carboplatin and paclitaxel did not improve overall survival or progression-free survival.”

The OUTBACK study was funded by the National Health & Medical Research Council of Australia. Mileshkin has reported no relevant financial relationships. Pierce has reported financial relationships with PFS Genomics and UptoDate. Penson has reported serving on advisory boards for AbbVie, AstraZeneca, Cancer Panels, Care4ward (unpaid), Eisai, Genentech, Intellisphere, Merck, Sutro Biopharma, Tesaro, Vascular Biogenics, WebMD; receiving research funding from Array, AstraZeneca, Eisai, Genentech, Regeneron, Sanofi Aventis, Tesaro, Vascular Biogenics, and receiving royalties from BMJ Publishing, UptoDate, Elsevier, Wolters Kluwer Health, and Wiley Blackwell.

ASCO Annual Meeting 2021. Abstract LBA3. Presented June 3, 2021.

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