Joyce Barlin, MD, Women’s Cancer Care Associates, Albany, NY, presents data from the Lunchbox trial, evaluating chemotherapy and radiation sandwich therapy vs standard-of-care chemotherapy for patients with advanced endometrial cancer at the 2023 Society of Gynecological Oncology’s Annual Meeting on Women’s Cancer in Tampa, FL.

The trial found that there was no different in overall survival or progression free survival for radiation followed by chemotherapy, compared with chemotherapy, followed by radiation, followed again by chemotherapy.

Transcript

Hi, my name is Joyce Barlin. I'm a gynecologic oncologist in Albany, New York at Women's Cancer Care Associates. I had the honor of presenting, as a featured oral poster, our randomized phase 3 trial, which was called the Lunchbox trial. I feel like every good trial needs a good name, and I've always been known of my passion for vintage lunch boxes. I kind of feel like my senior superlative in residency was most likely to steal their children's lunchbox. If I had a trial that included an arm that was sandwich therapy, what else to call it, but Lunchbox trial? This is a trial in advanced endometrial cancer, and it was really born out of curiosity, after graduating from fellowship in 2014.

In fellowship, we supported kind of the ASTRO guidelines, which demonstrated in 2015 support for chemoradiation followed by chemotherapy for advanced stage endometrial cancer. We really weren't sure how to go ahead and give those, whether they should be together or sequential, or if it should just be 1 modality versus another. Putting this in context of the fact that we were awaiting results from GOG-0258 as well as PORTEC-3. Those did end up resulting over the course of the trial.

This trial opened for enrollment in 2015 in July, but then later, as the trial was already open, PORTEC-3 resulted. As a reminder to everyone, that included some early-stage endometrial cancer patients, and that was a comparison of radiation alone to chemoradiation followed by chemotherapy. That demonstrated that chemoradiation followed by chemotherapy was superior. But again, that was a different patient population and a different control arm of radiation only. Fast-forward to GOG-0258, and that really showed in advanced endometrial cancer, with some inclusion of early-stage cytokine release syndrome (CRS) and clear cell, and so then when GOG-0258 resulted, that compared chemoradiation followed by chemotherapy to chemotherapy alone, neither was superior. Then standard of care was considered to be chemotherapy alone.

We do not always put into practice what the randomized data has shown. I was surprised, having graduated from fellowship, to find that in practice nationwide, the most common modality of treatment for advanced endometrial cancer was sandwich therapy, so chemotherapy followed by radiation, followed by more chemotherapy. I asked the clinical question of, should it matter? Should you do chemo-radiotherapy (RT) followed by chemo, or should you do sandwich therapy? There was no kind of randomized data available. That was my quest that I tried, having graduated recently from training, and over the course of 6 years and 8 institutions and 42 patients and a futility analysis later, we did stop results early because there was no difference observed, whether it be in progression-free survival or overall survival.

What does that mean from a clinical perspective? I think that we are still not sure how to treat advanced endometrial cancer. I think a purist, in the interpretation of GOG-0258, would say that chemotherapy alone would be sufficient, but in practice, it certainly seems like providers feel inclined to provide both modalities. I think this adds to the literature that you can certainly do chemoradiation followed by chemotherapy. You can do sandwich therapy. I think another kind of regimen that is very popular is 6 cycles of chemotherapy, a la GOG-0258, and then re-scan and do subsequent consolidative radiation treatment.

The answer is it remains as clear as mud, but it's important to do these clinical trials, to ask the questions, to have support from your colleagues, to have perseverance and adaptability, and to keep asking the important clinical questions.

Source:

Barlin J. “Lunchbox trial: A randomized phase III trial of cisplatin and irradiation followed by carboplatin and paclitaxel vs. sandwich therapy of carboplatin and paclitaxel followed by irradiation then carboplatin and paclitaxel for advanced endometrial cancer.” SGO Annual Meeting on Women's Cancer; March 25-28, 2023; Tampa, FL

Matei D, Filiaci V, Randall ME, et al. Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. N Engl J Med. 2019;380(24):2317-2326. doi: 10.1056/NEJMoa1813181.

de Boer SM, Powell ME, Mileshkin L, et al. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): Final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018;19(3):295-309. doi: 10.1016/S1470-2045(18)30079-2.