Oncology for the Inquisitive Mind

Last week Josh and Michael discussed early ovarian cancer, but as is always the case many patients either do not respond completely to treatment of their early disease or present with advanced disease and thus are robbed of that chance. In these patients, getting the treatment right is a complex discussion but a vital one. In this episode, we discuss two studies in the advanced ovarian cancer space, a space that could still use more love, but has seen developments in recent years.

Studies Discussed in Today's Episode

AURELIA

ICON4

Our Back to Basics odyssey nears its end, a journey just as epic as Matt Damon's (we think so, anyway). As we enter the final stretch, we discuss ovarian cancer, a cancer with significant mortality and morbidity despite advances in treatment. In this episode Josh and Michael discuss two studies in the early ovarian cancer space, a topic fraught with challenges as unique as Scylla and Charybdis.

Studies Discussed in Today's Episode

ICON7

PAOLA-1

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On this episode, Josh and Michael examine the treatment of advanced melanoma, the condition that blazed the trail for immunotherapy to change the face of cancer treatment. However, immunotherapy is not the ONLY treatment for melanoma, as a significant proportion of cases also harbour a BRAF mutation. So, if you have someone with such an example, what do you do? How would you sequence your treatment? This question, and a reflection on the incredible beginnings of immunotherapy is coming to you on today's episode.

Studies Discussed in Today's Episode

Checkmate 067

DreamSeq

Our guest today is someone whose work touches almost every corner of oncology: from the exam room to the lab to the systems we work within.

Dr Narjust Florez, MD, FASCO, is a thoracic medical oncologist at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School, where she treats young patients and women with lung cancer and leads a research program spanning early diagnosis, clinical trials, and cancer health disparities. She's the Associate Director of the Cancer Care Equity Program and leads the EQUAL Study, which tackles disparities in lung cancer screening among...

In this episode, Michael and Josh delve into the world of early melanoma. Some may think that melanoma has had its moment in the sun (pun slightly intended) and that other cancer treatments are passing it by. But in this instance, you can teach an old dog new tricks, an old immunotherapy dog, to be precise. In addition, one of today's studies has Michael's favourite design of any trial: see if you can figure out which one!

Studies Discussed in Today's Episode

KEYNOTE-054

NADINA

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If you like cemiplimab, you will like this episode. Since its introduction, cemiplimab has become the mainstay of treatment for cutaneous SCC, the most common non-melanoma skin cancer likely to attend an oncologist. Cemiplimab's scope is expanding; once reserved purely for the locally advanced or metastatic setting, evidence is emerging for its efficacy in the neoadjuvant setting. Today, Josh and Michael explore the use cases for cemiplimab in cSCC

NOTE: this episode was NOT sponsored by cemiplimab!

Studies Discussed in Today's Episode

Migden et al. (2018)

Gross et al (2023)

For over a decade, sorafenib remained unchallenged as first-line therapy for hepatocellular carcinoma, based on the SHARP trial, which showed survival increasing from 7.9 to 10.7 months. This demonstrated modest efficacy in a disease notoriously resistant to systemic treatment. That drought broke in 2020, when IMbrave150 demonstrated that atezolizumab plus bevacizumab beat sorafenib outright, pushing median survival past 19 months and putting immunotherapy on the map for liver cancer. Two years later, HIMALAYA proved that a single priming dose of anti-CTLA-4 could unlock durable responses, with the STRIDE regimen nearly doubling five-year survival compared with sorafenib. Then IMbrave050 asked whether that success could...

Until recently, biliary tract cancers were relegated to orphan cancer status: rare cancers such as cholangiocarcinoma and gallbladder cancers. These aggressive malignancies were lumped together, historic trials were small, and patients were stuck with gemcitabine-cisplatin chemotherapy as the only real option, a regimen that hadn't changed for almost a decade. Then two trials cracked the field open. BILCAP, reported in 2019, gave resected patients their first evidence-based reason to take adjuvant capecitabine, pushing median survival from around three years to over four. And in 2022, TOPAZ-1 became the first trial to prove immunotherapy has a place in biliary cancer. Durvalumab was...

On today's episode, we have a very special guest: Dr Kerry Jewell is a nuclear medicine physician, medical advocate and very good friend of the show, who recently published her debut novel A Little Unwell. Kerry is wonderfully eloquent doctor who frequently chooses violence when with dealing with Michael, whom she has known for his entire medical career. Today, Kerry discusses her book, working as a nuclear medicine physician, provides some of her amazing wisdom for our oncology colleagues and gets candid about a recent, heart-breaking diagnosis.

A Little Unwell available here: https://www.amazon.com...

This episode is the ASCO 2026 Plenary Episode. This week, all of the pivotal, game-changing, life-changing trials are discussed here. Some describe the plenary session as practice-changing, and we will always agree that better treatments with significant improvements in life expectancy and quality of life need their time in the spotlight.

Today, five trials are discussed, including SARC041, a liposarcoma study utilising the CDK 4/6 inhibigtor abemacicilib. Our second study is HARMONI-6, investigating whether ivonescimab plus chemotherapy is effective in patients with advanced squamous non-small cell lung cancer. Our third, almost like something written for an opera (LIBRETTO0...

This week, Josh and Michael's ASCO 2026 coverage looks at "Agents of the Future", trials of intrigue, promise and potential beyond its status. This episode also sheds light on more orphan status cancers like head and neck cancer, basket cohort studies, resistant EGFR lung cancer, metastatic colorectal cancer and hepatocellular carcinoma.

One more episode left of this arc - The Plenary! Stay tuned.

Studies Discussed in this Episode

OrigAMI-4

WU-KONG28

A Phase 1/2 Study of JK06, a 5T4-Targeted Antibody Drug Conjugate (ADC), In Patients with Unresectable Locally Advanced or...

ASCO 2026 is done, and Michael and Josh have created a marathon episode for you all. This week we cover "Agents of the Present", where we summarise all the important trials with updates, overall survival and progression-free survival data that could influence your practice.

They cover immunotherapy, lifestyle interventions, pan-PI3K inhibitors, rare cancers (such as uveal melanoma), and antibody drug conjugates, to name a few. All the cancer types are covered, including genitourinary, gynaecological cancers, breast, colorectal, lung and lifestyle interventions!

Two more episodes to come!

Studies Discussed in this...

This week, we take a quick trip to Stockholm, Sweden, where ESTRO (European Society for Radiotherapy and Oncology) took place several weeks ago. A/Prof Steven David digs deep into the latest updates in the breast cancer radiation space, including hyperfractionation of treatment, the utilisation of AI for radiation planning (Archery Trial), and the DBCG RT Natural Trial, which examined whether omitting partial breast irradiation (PBI) after breast-conserving surgery was safe in those over 60 (spoiler: you should still give PBI).

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This episode tells the story of how one man, Jake Messier, who is living with metastatic male breast cancer, is challenging the stigma surrounding this disease, which affects 1% of all breast cancer patients. It's an important reminder that not all cancers are funded and researched equally, and that behind every statistic is a person trying to live a normal life.

Jake has used his lifelong PR skills to turn what is a diagnosis unlike any other into a conversation about equity, resilience and a deep societal stigma. This conversation should also serve as a reminder of...

This week, we take a "back to the future" look at the early-stage pancreatic cancer phase, a relatively stagnant area in terms of pivotal trials. The two trials are the ESPAC4 trial, which examines doublet chemotherapy in pancreatic cancer, and Josh does a traditional deep dive into the world of neoadjuvant chemotherapy. He highlights ESPAC-5, PREOPANC-2, and the TAPS consortium, to name a few. A complicated but overall evolving field.

Studies discussed in this episode:

ESPAC-4

FOLFOXIRI

PREOPANC-2

ESPAC-5

TAPS (Trans-Atlantic Pancreatic Surgery (TAPS) Consortium Study)<...

Today, we accidentally skipped early pancreatic cancer and jumped straight to advanced pancreatic cancer. It was a sombre episode, with clinicians and advocates screaming for better treatment options for this cancer. While small incremental advances have been made, the holy grail remains elusive.

Today our focus is on NAPOLI-3, the use of liposomal irinotecan (NALIRIFOX), and PANOVA-3, where TTFields are used in combination with gemcitabine/abraxane. A good conversation, though the current premise is sad. Hopefully, as time moves on, this conversation will be more optimistic.

Studies discussed in this episode:

...

On today's episode, Josh and Michael "advance" in their ongoing GI journey, as Michael continuously insists on saying, to discuss advanced gastric and GOJ cancer. Historically, an orphan disease with a very poor prognosis, perhaps the first rays of light are beginning to shine on this difficult-to-treat cancer type. Immunotherapy has been well established as standard of care, but are there any new agents that are emerging in this space? As always, the answer to that question is "yes," and as usual, the agent in question is trastuzumab deruxtecan. Listen on for all the surprising details, even more awful...

This week, as we enter our 200th episode, Michael and Josh continue their journey through the alimentary canal, exploring the world of stomach cancer. Gastric cancer has been notoriously difficult to treat, with a thirty-year grace period of multiple trials seeking an appropriate regimen that reduces recurrences while remaining effective. This episode gives you all the answers, and just when we thought everything was settled, immunotherapy enters the fray with MATTERHORN.

Studies discussed in this episode:

FLOT4-AIO

MATTERHORN

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Good therapeutic options for metastatic colorectal cancer are limited after the fluoropyrimidine-based options are exhausted. This week, we explore the role of trifluridine-tipiracil (Lonsurf) and bevacizumab (VEGF inhibitor), and a newish kid on the block, fruquitinib, an oral tyrosine kinase inhibitor and vascular endothelial growth factor receptor. While not perfect, they do represent later-line options for patients

Studies discussed in this episode:

SUNLIGHT

FRESCO-2

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Today's episode, like several of the greatest cult classics, comes a bit earlier than anticipated. Before we wrap up our epic recap of the colorectal space, we will give you a little taster of our UGI series with a look at early oesophageal cancer, focussing on the chemotherapy backbone and whether immunotherapy has any place in this space. Spoiler alert (as always): it does.

Studies discussed in this episode:

ESOPEC

Checkmate 577

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Metastatic Colorectal Cancer has a dearth of targetable mutations that have effective outcomes. This week, Michael and Josh see whether the wonder drug (trastruzumab deruxtecan) works in HER2-expressing colorectal cancer. Michael takes a more positive tone, with the recycling of aspirin to reduce recurrence risk for PI3K pathway cancers.

Josh promised he will have the right audio this episode - thanks to our astute listener who told us last time!

Studies discussed in this episode:

ALASCCA

Destiny-CRC01

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UPDATED WITH CORRECT AUDIO

While Michael daydreams of getting a haircut, this week's topics are slightly more conventional as we explore the role of more targeted agents in metastatic colorectal cancer. KRAS and BRAF mutations in colorectal cancer were historically prognostic; this has now shifted with targeted therapies available for both. In the context of metastatic colorectal cancer, BRAF mutations account for up to 10% of cases and are associated with significantly poorer overall survival compared with wild-type (WT) counterparts. The median overall survival in many cases of metastatic disease was under 15 months. Five years ago, there...

Historically, colorectal cancer treatment has been fairly standard, but this has shifted over the past decade with the introduction of targeted therapies. This week, our focus is on patients with microsatellite instability (dMMR) colorectal cancer, a small but meaningful cohort. This condition affects up to 15% of patients, many of whom carry germline mutations in the MLH1 and MSH2 genes, which simply means that cells can't recognise and fix spontaneous mutations. Historically, these cancers are less responsive to chemotherapy.

This week, we explore two immunotherapy regimens - pembrolizumab, ipilimumab and nivolumab.

Studies discussed in...

Metastatic colorectal cancer is one of the leading causes of cancer-related deaths and among the most common types of cancer worldwide. Chemotherapy remains the main treatment, but the question is: how can we make it more effective without increasing toxicity?

This week, we explore the intensification of chemotherapy in an effort to improve overall survival. The second topic involves the use of monoclonal antibodies and targeted therapy to enhance existing regimens. Josh also conducts his characteristic deep dive, examining the evolution and application of the monoclonal antibodies cetuximab and panitumumab over the past 15 years. He a...

Professor Jonathan E. Rosenberg, MD, serves as the Chief of the Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Centre (MSKCC). He is a prolific researcher and author, holding multiple titles including Attending Physician at MSKCC, Professor of Medicine at Weill Cornell Medical College, and the Enno W. Ercklentz Chair in Genitourinary Oncology.

Today, Jonathan explores metastatic urothelial cancer, discussing the current landscape and available treatment options, emphasising that a single approach may not be suitable for all patients. We also cover early bladder cancer and non-invasive muscle-invasive bladder cancer (NIMBC).

For more...

The DYNAMIC duo are back, with Michael climbing the "Everest" of oncology and exploring the role of CTDNA in stage two colorectal cancer. Josh has the easier job of exploring neoadjuvant immunotherapy (ipilimumab and nivolumab) in dMMR advanced colorectal cancer.

Both are excellent trials, and a worthy addition to your reading list.

Don't forget to check us out on YouTube if that's your thing!

Studies discussed in this episode:

DYNAMIC-II

NICHE-2

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This week, we explore early colorectal cancer. Maybe it’s just this week, but there were plenty of “IDEAS” around. Michael highlights the importance of choosing an appropriate adjuvant regimen, whether that be FOLFOX or CAPOX. Josh digs a bit deeper and, as the name suggests, looks at whether patients with liver metastases can be cured with chemotherapy and a liver transplant.

Studies discussed in this episode:

IDEAS

TransMET

EORTC

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Mesothelioma can strike at any time, but it most commonly affects those in their 70s, with cases continuing well into the 2030s. The time from exposure to diagnosis can be up to 60 years. This week, we explore treatment options for pleural mesothelioma, including ipilimumab and nivolumab, and consider whether chemotherapy and bevacizumab work for mesothelioma as well. The MAPS trial was published in 2016, while Checkmate was published in 2022.

Studies discussed in this episode:

MAPS

Checkmate 743

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This week, we return to our regular programming with a back-to-basics exploration of extensive small-cell lung cancer. A notorious killer and an aggressive type of lung cancer, it has seen new treatments developed at a faster rate than in the last twenty years combined.

We explore tarlatamab, a bispecific delta-like ligand 3-directed T cell engager. The results show that, in the second-line setting, it improves overall survival (spoiler alert). The second study is IMforte, utilising lurbinectedin plus atezolizumab in the first-line setting for extensive-stage SCLCa. Again, a positive trial showing an improved median overall survival of 13.2...

Today, our guest is a transformative figure in bowel cancer treatment. Professor Jenny Seligmann, a Consultant Medical Oncologist and Professor of Gastrointestinal and Translational Oncology at the University of Leeds, is renowned for leading the groundbreaking FOxTROT and ARIEL trials. These studies challenged traditional practices by demonstrating the advantages of administering chemotherapy before surgery, a change now saving lives and influencing worldwide protocols. As a devoted mentor and a prominent participant in Cancer Research UK’s initiatives, she joins us to explore how we can personalise cancer treatment more effectively and discuss the future prospects for gastrointestinal cancer therapies. Welc...

In our final take on ESMO 2025, we talk about Genitourinary Cancers. This was a dense area with numerous trials. Today we explore distimiab vedotin in those with advanced bladder cancer, the role of combining lutetium with an ARPI in advanced prostate cancer, whether de-escalation of docetaxel in high volume prostate cancer was just as efficacious as the regular six cycles, immunotherpay plus bCG in non-muscle invasive bladder cancer, adjuvant durvalumab in renal cell caricnoma and the perioperaive role of enforumab vedotin for muscle invasive bladder cancer.

We're out of breath just listing off these trials, and...

ESMO Episode 6 is here! The longest award ceremony in the world continues. This episode covers colorectal cancer, a cancer stream that has relied heavily on the same three drugs for the past twenty-five years.

We cover the golden pinnacle of real-world use cases for CTDNA, neoadjuvant immunotherapy in those with proficient MMR colorectal cancer, whether Zanzalimab helps in refractory colorectal cancer, and much more.

Studies:

BREAKWATER

NEOADJUVANT IMMUNOTHERAPY (pMMR)

STELLAR-303

CHECKMATE 8HW

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We're back, baby! Michael and Josh predicted their ESMO journey would have eons to run, and they weren't wrong! For our first episode back in 2026, we revisit the important coverage of ESMO 2025, highlighting advances in upper gastrointestinal tract and hepatobiliary cancers.

This episode covers FGFR inhibitors (Bemartizumab), updates on the MATTERHORN trial, the use of immunotherapy with trastuzumab and FLOT in HER2-positive localised oesophageal carcinoma, and investigates the use of TKIs and the novel drug nofazinlimab for those with unresectable or metastatic hepatocellular carcinoma.

A jam-packed episode that aims to over-deliver on...

This week, we discuss neuroendocrine tumours and melanoma as our ESMO 25 journey continues. Trials for neuroendocrine cancers include HIF-2 alpha inhibitors, targeted alpha therapy, and a classic anti-PD-1/TIGIT bispecific antibody combined with standard etoposide and cisplatin chemotherapies.

Melanoma is once again seeking that elusive breakthrough: the second-line therapy that demonstrates immunotherapy is not a one-time opportunity. We also highlight both the BNT111 RNA-based lipoplex immunotherapy targeting agent and the question of whether early discontinuation of immunotherapy could be beneficial.

Studies:

LITESPARK-15

IMPRESS-Norway trial

Abstract 1510M0

For our third instalment of ESMO 2025, we explore lung cancer in all its glory, including small cell, mesothelioma and non-small cell lung cancer.

Studies:

DeLLphi-303

SOHO-01

ALBATROS

PAULIEN

DREAM3R

OptiTROP-Lung04

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Art courtesy of Taryn Silver

Music...

ESMO 2025 continues this week with coverage including early breast cancer, metastatic breast cancer and gynaecological malignancies. A mammoth episode covering giants and pioneers of the oncology world.

Studies:

SOLTI-RIBOLARIS

POSITIVE

monarchE:

DESTINY-Breast11

evERA

ASCENT-03

TROPION-Breast02 trial

ROSELLA

DICE trial

ENGOT-ov65/KEYNOTE-B96 study

ROSELLA

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After a short break for some pretty major life changes (more details in the episode), Josh and Michael return to tackle the best and brightest of ESMO 2025. With support from MSD, our dynamic duo play host to the inaugural Oncology for the Inquisitive Mind Awards. Today, they look at studies in pre-clinical science, supportive care and rare cancers to find their favourite studies amidst the goldmine that was this year's European Oncology Extravaganza.

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In this episode, the focus shifts away from the more "garden-variety" non-small cell lung cancer and to its less common, frequently more aggressive sibling, small cell lung cancer. Here, Josh and Michael examine the management of limited-stage small cell lung cancer, which while accounting for a minority of cases, is no less interesting and potentially confusing.

Studies discussed in this episode:

PCI Meta Analysis

ADRIATIC

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On this week's episode, Josh and Michael exchange the established treatment landscape of EGFR and ALK mutant NSCLC for the developing management of disease harbouring KRAS and MET mutations. The most common mutation meets one of the least common in this battle of therapeutic tenacity.

Studies discussed in this episode:

INSIGHT-2

KRYSTAL-12

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In this episode, Michael and Josh take a dive into the world of driver mutations, looking at two of the most clinically consequential: EGFR and ALK mutations. The work done in these areas has led to treatments that represent incredible advances over chemotherapy. How incredible? You'll just have to listen and find out.

Studies discussed in this episode:

MARIPOSA

CROWN

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