Today, we interview Dr. Erica Mayer as our first guest in the "On the Road" mini-series. Dr. Mayer is a renowned breast cancer oncologist at the Dana Farber Cancer Institute. Each week for the next seven weeks, Michael and Josh will introduce a new guest to share their wealth of experience, expertise and wisdom, covering all the essential topics from career development, mentorship and necessary trials and challenges in the oncology world.

Dr. Mayer graduated from Harvard Medical School and completed a fellowship in Medical Oncology at the Dana-Farber Cancer Institute. Erica is the Director of Breast Cancer Clinical Research and is involved in multiple trials, which she discusses in this interview, along with the role of the PACE trial, CDK 4/6 inhibitors, CT DNA and many other important facets of the breast cancer world.

The Kinghorn Cancer Centre and The Beverley Alt Scholarship proudly support this mini-series.

2023 has been a year of highs and lows, a calendar of peaks and troughs, an epoch of mountains and valleys (all right Michael, put the thesaurus away...). From standing ovations for enfortumab vedotin and vorasidenib, to the ongoing black hole that is effective treatments for pancreatic and hepatocellular carcinomas. However, through it all the brightest minds in the field have continued to stoke the fires of hope with the development of novel antibody-drug conjugates, immunotherapies and clever applications of established treatments.

On this episode, their final of 2023, Michael and Josh return to the world of recent fan favourite, enfortumab vedotin (EV). Not content to sing its praises from every rooftop, our intrepid hosts take the necessary step of examining the common and sometimes severe manifestations of dermatological toxicity deriving from EV. With the assistance of a recently published guideline, they examine the presentation, assessment and management of skin toxicity.

From all of us at OftiM, we would like to thank you for joining us throughout 2023, and we wish you a very happy festive season.

Oncology for the Inquisitive Mind would like to issue a formal mae culpa to our listeners. You have joined us for over 12 months and over 80 episodes and listened to our ramblings and bad jokes. And it has taken 80 episodes for us to realise we have neglected the crucial and exciting subject of metastatic triple-negative breast cancer (TNBC). But fear not! We will rectify this egregious oversight with immediate effect. TNBC remains the scourge of the usually more optimistic breast cancer space. However, the fight of the world's oncologists continues across all fronts, and TNBC is no different. In today's episode, Michael and Josh will discuss the twin pillars of modern anti-cancer therapies: antibody-drug conjugates (sacituzumab govitecan) and immunotherapy (pembrolizumab). As so often the case, this is a growth area of medical oncology and one that we are very excited to (finally) address.

For patients with advanced cancer, early-phase trials may represent the last best hope of significant anticancer response. For clinicians, every early phase trial holds virtually unlimited promise and hope of becoming the next immunotherapy or hot antibody-drug conjugate. However, early-phase trials also come with significant uncertainty of efficacy, toxicity, and even dosing.

A recent Limbic article (link below) reported on an article published in ESMO Open that investigated the burden of "time toxicity" for patients enrolled in early-phase clinical trials, and advocated for this to be minimised. While it is essential to consider logistic factors and patient preferences, early-phase trials are frequently more inflexible compared to phase II or III studies and are constructed as such to ensure patient safety in the face of significant unknowns.

In this episode of Fireside Chats, Michael and Josh discuss the pros and cons of attempting to streamline early phase trials, if possible, and what can be done to minimise a trial's impact on a patient's day-to-day and quality of life.

San Antonio Breast Cancer Symposium is here, and this year, OFTIM (Oncology for the Inquisitive Mind) is bringing you the latest and greatest in all things breast cancer. With over 10000 attendees, the research and vibrant discussions did not disappoint, with updates, controversies and complexities. Taking centre stage were PIK3CA mutation treatments, updates on CDK4/6 inhibitors and the age-old question - does exercise improve outcomes for our patients?

Today, OFTIM celebrates its 80th episode and presents its ESMO23 plenary session, including two practice-changing, paradigm-shifting trials. The first investigates the EGFR mutation Non-Small Cell Lung Cancer world with new drugs (amivantamab and lazertinib) to treat patients hose who progressed on osimertinib. The second trial is the EV-302/KEYNOTE-A39, which explores whether enfortumab vedotin (ADC) and pembrolizumab (immunotherapy) can best-platinum-based chemotherapy. No prior trial has ever done this, so the stakes are high. As the little engine once said, "I think I can", and, we, too, continue to see seismic shifts in cancer treatment in our quest for better therapy. For now, the OFTIM team is signing out and taking a small break after daily reporting, but we hope you loved it and can't wait to return with more from the fascinating world of Medical Oncology.

As Oncology for the Inquisitive Mind's coverage of ESMO 2023 winds down, we bring some of the best presentations covering gynaecological cancer. An area of oncology that in many cases remains mired in the pre-immunotherapy and pre-targeted therapy ages, ESMO brought some much-needed positive trials in the areas of cervical cancer, as well as an interesting (albeit negative) study of the PARP-inhibitor olaparib that highlights some of the more practical challenges of running an international phase 3 study. As always, outcomes can improve, but progress in this critical area is always welcome.

Since the early development of immunotherapy, metastatic melanoma has been the golden child of medical oncology. In recent years, similar outcomes have been seen with immunotherapy in non-melanomatous skin cancers. Cemiplimab is now a standard of care for patients with locally advanced, unresectable or metastatic cSCC, and is particularly effective in patients with cancer driven by UV-induced DNA damage. However, oncologists and researchers are always looking for new and better ways to use established treatments. At ESMO 2023 two papers took this approach; one examined moving immunotherapy to the neoadjuvant space, while another added a venerable EGFR inhibitor to treatment of advanced cSCC. However, the undoubted star of this show is the long-term results of tebentafusp, the first efficacious treatment of a subtype of the notorious uveal melanoma. ESMO 2023 truly had something for everyone, and the melanoma and skin cancer areas were no exception.

Non-small cell lung cancer continues to show massive promise with new trials, better designs and exciting utilisation of existing therapies. Michael and Josh explore immunotherapy in a "sandwich setting" where nivolumab is given before and after surgery. Datopotamab deruxtecan, the new kid on the block, takes on the second-line champion docetaxel. Who will win, and will docetaxel finally be dethroned? And potentially the most promising and exciting addition to this lineup is AZD7789, a new bispecific antibody TIM-3 being added to existing immunotherapy to try and resensitise cancer to PD-1 inhibitors!

Metastatic colorectal cancer has an average overall survival of three years. With limited treatment options as standard of care or effective targetable mutations, ESMO23 shined, providing answers to unanswered questions and a potentially brighter future for this cancer. Concerningly, we are seeing higher rates of colorectal cancer in lower and middle-income countries and those under the age of 50. We explore sotorasib in KRASG12C mutated cancers with panitumumab, the use of aspirin to reduce the risk of cancer recurrence and whether triplet therapy is better than double in potentially resectable colorectal cancer.

Colorectal cancer remains the bread and butter of many an oncologist, but its commonality belies its complexity. In early and advanced disease alike, there remain many permutations, considerations and controversies regarding optimal treatment. What is the best way to treat potentially-resectable colorectal cancer with liver metastases (CRLM)? Is there a way to increase the responsiveness to immunotherapy in patients with proficient mismatch repair (pMMR)? And are we moving to a brighter future where patients with deficient MMR colorectal cancer could avoid surgical management through the miracle of immunotherapy? Ultimately, no one study is going to answer these questions, but with ESMO 2023, we may be starting to peel back the layers of this onion.

Next up on the ESMO 2023 rollercoaster is an episode that is likely to be the shortest in our series: upper gastrointestinal and hepatobiliary oncology. As always, this remains a very challenging subarea of medical oncology, both in the clinical and trial spheres. However, our esteemed colleagues at ESMO remain undaunted by this challenge, and thus several studies of interest bear discussing. Will any of these studies lead to massive upheavals for clinicians and patients alike? For that answer, you'll have to listen on.