Hi everyone. Apologies for being late in posting the blog for the month of September, but I guess better late than never. I finally finished my medical oncology training and graduated with a PhD from Nagoya University last month. But most important, last month was the month of ESMO congress in Madrid! In order to help you separate signals from noise coming from the congress, we have summarized the highlights from the meeting in a 2 part video. Please find the highlights from GU cancer and melanoma in this part 1 and highlights from lung, breast, GI cancers and others in part 2. I will discuss some studies here that have been published in the month of September and were not covered in detail in my videos.

Is nivolumab ipilimumab better than nivolumab? Well, we didn’t test that.

Nivolumab plus ipilimumab has shown improved overall survival versus ipilimumab alone in metastatic melanoma. Cleverly, there was a nivolumab arm and the study was powered for combo versus ipilimumab as well as nivolumab versus ipilimumab arms but not combination versus nivolumab arm. In a descriptive analysis, however, the combination versus nivolumab arm didn’t show any significant difference in survival. Thus, as we discussed in this commentary, nivolumab followed by ipilimumab would be a wise strategy and should, in fact, have been the ideal comparison against the combination in the RCT.

Revisiting the role of maintenance therapy: what's the purpose?

Many PARP inhibitors are being developed and tested in ovarian and breast cancers. Rucaparib follows the suite and demonstrates in the ARIEL 3 trial that it improved PFS versus placebo when used as maintenance therapy. Again, overall survival is not known and improving PFS versus placebo as maintenance is not a high enough bar. This has again been discussed in detail in this commentary and this video. I can't understand how it is okay for us to keep getting excited about drugs that are expensive, that are taken as "maintenance therapy" and yet have no data on whether they'll help you live longer.

When do we say enough is enough?

When do we decide that we need better outcomes than a mere 1.3 month prolongation in progression-free survival versus placebo with more than $13K a month and added toxicities? That's a question regulatory agencies, oncologists and patients need to decide after the publication of results from the RANGE trial testing ramucirumab plus docetaxel versus placebo plus docetaxel as a second line treatment of urothelial cancer. Fortunately, immunotherapy has shown good outcomes in this setting and probably RANGE will be irrelevant but well, you never know because I have seen people use this drug in colorectal cancer where the evidence is equally poor.

Adjuvant treatment of RCC

The goals of treatment and risk-benefit thresholds in adjuvant setting of cancer treatment are very different from those in metastatic setting. After surgical resection of renal cell cancer, patients are tumour-free and not all of them relapse. So if we plan to use a drug in these patients, we should be sure that the benefits undoubtedly surpass the toxicities and extra financial burden. This is all the more important because these drugs can be used again upon relapse. Sorafenib was tested in this setting and failed to improve DFS, much less OS. Sunitinib was tested in 2 trials and a meta-analysis showed it failed to improve OS as well as DFS. In a new trial, pazopanib followed the trend and failed to improve DFS. My surprise? Sunitinib received a 6-6 vote in the FDA ODAC. Why wasn’t it a clear no? 

How much is life worth?

This is a difficult question that we had avoided until recent years but with the approval of CAR-T cell therapy, we have no choice than to acknowledge and address the elephant in the room. With $475,000 price tag and impressive response rates but still no long term data on survival, some difficult questions need to be asked and hype addressed. Fortunately, two excellent commentaries have been published and I don't need to speak further on this. Please read this commentary on JAMA and this on Nature Reviews Clinical Oncology that highlight the promises (or lack of) and complexities of this super expensive treatment.

And how much does it cost to bring a cancer drug to market?

Apparently, the median cost of developing a single cancer drug was $648.0 million, much lower than the previously reported figure of $2.7 billion.  There have been some criticisms to this study to which the authors have responded here. I think this analysis is as reasonable as the authors could have been; the main problem is that the R&D costs of the industry are still not transparent. Transparency of those costs would be the best rebuttal to this analysis, if anyone wanted to.

Women's health is more than reproductive health.

"Women's health is more than reproductive health. Why does this phrase still need to be repeated?" asks Ophira Ginsburg in this emphatic commentary. She sheds light on some less-discussed topics related to women's cancer in low-and middle income countries and proposes a path to progress in this open-access piece.

Let me take a selfie

This was actually published online sometime ago but I didn't have the chance to share. In a viewpoint published in JAMA Oncology, we show the pitfalls of basing our decisions on subgroup analysis using the case example of pemetrexed in non-squamous non small cell lung cancer. While toxicity profile is not under debate, the superior efficacy of Pemetrexed versus gemcitabine based on nonsquamous histology could probably simply be an artifact of multiple comparisons. This was also covered by Medscape, which you can read here.

Bishal Gyawali, MD, PhD completed his training in medical oncology at the Graduate School of Medicine, Nagoya University, Japan, and obtained a PhD as a Japanese government scholar. He works as a medical consultant at Anticancer Fund, a not-for-profit organization based in Belgium as well as holds an affiliation at Institute of Cancer Policy, UK. His areas of clinical and research interests include evidence-based oncology practice, global oncology, cancer policy, cancer management in resource-limited settings, financial toxicities of cancer treatment, clinical trial methods and supportive treatment of cancer. He has no conflicts of interest to declare. Dr Gyawali tweets at @oncology_bg. Read his previous blog posts here.